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The Rockefeller University Center for Clinical and Translational Science
Minutes of the Advisory Committee on Clinical and Translational Science (ACCTS)
July 20th, 2011
Voting Members Present: Robert Darnell – Chair, Ed Barbour, Jon Blumenfeld, Edgar Charles, Barry
Coller, Emil Gotschlich, Peter Holt, Andreas Mauer, Melissa Offenhartz, Barbara O’Sullivan, Neil Renwick,
Andrea Ronning, Sarah Schlesinger, Terry Solomon, Maija Williams, Knut Wittkowski
Invited: Donna Brassil, Ross Gillman
_______________________________________________________________________________
The meeting was called to order at 2:31 pm
_______________________________________________________________________________
1. Approve minutes from the June 1, 2011 ACCTS meeting
2. Initial Reviews
Kemal Marc Akat
KAK-0750 - Small RNAs in the
Cardiovascular System in Health and
Disease
[Reviewer: Michelle Lowes]
Scientific Initial Review
What are the background and goals of study?
This is a pilot study to understand micro RNA expression profiles in cardiac tissue. Most prior studies
on heart tissue used miRNA arrays, and have not taken into account regional differences in cardiac
tissues, so the investigators wish to use state of the art miRNA analysis platforms developed in the
Tuschl lab.
They will analyze samples collected and stored by collaborators Dr Paul Schulze at Columbia
University, NY, and Dr Dobromir Dobrev at University Mannheim, Germany
Patients 10-20, F and M will be included, and disease cardiac samples obtained "during clinically
indicated surgery unrelated to this study", from different areas of the heart. Samples from healthy
volunteers will be obtained from cadaveric donors.
If this is a clinical trial, please specify:
Intervention: N/A
Primary endpoint: Difference in small RNA expression.
Secondary endpoint:
To validate or extent the results obtained from the tissue small RNA profiles, we will look at the
following additional parameters (for selected samples):
1. Differences in small RNA profiles in blood samples using the same basic protocol for deep
sequencing.
2. mRNA profiles using arrays looking for changes in expression miRNA targets
3. miRNA/mRNA situ hybridization to get a higher spatial resolution
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4. Tissue proteomic techniques
What are the major risks? Nil
Statistical Analysis (optional: comments in addition to Biostatistician review)
Statistical plan is very brief, sample size is not discussed
What is the potential significance of the study?
This could generate very useful and interesting data.
Ratings:
Scientific Merit:
Priority:
Resource Intensity:
High
High
Low
Recommendation
Reviewer's Recommendation of Submission
Approve with recommendations
Reviewer's Comments
The sample size should be discussed, even for a pilot study.
The IRB- approval from Germany is in German.
The IRB-approval from Columbia is for heat failure only- is this the only group to be studied from
Columbia? Please clarify.
The consent forms from Columbia and Germany should be reviewed to ensure the patients that are
donating tissue are aware and approve of the collaborations.
There is another German document for Dr Akat Mannheim that was not clear why it is attached, as he
does not appear to be a collaborator.
Please clarify how the cadaveric normal heart tissue will be collected.
Indication of Review Completion
Yes
Date the Review was completed: 07/13/2011
Action: Approved
Niroshana Anandasabapathy
A Phase 1 Safety, Pharmacokinetic, and
Immunologic Study to Evaluate CDX-301
(rhuFlt3L) in Healthy Volunteers
[Reviewer: Lynn B. Dustin]
Scientific Initial Review
What are the background and goals of study?
This study is a phase I clinical trial of a new formulation of a recombinant protein, FMS-like tyrosine
kinase-3 ligand (Flt3L). Flt3L promotes growth, differentiation, and mobilization of hematopoietic stem
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cells, immature thymocytes, and dendritic cells. In animal models, recombinant Flt3L can cause varied
effects on immune responses, sometimes enhancing them and sometimes inhibiting them.
Recombinant human Flt3L was initially developed as a drug candidate about 10 years ago by
Amgen/Immunex, and that formulation has undergone human trials in the setting of healthy volunteers
and cancer patients. The drug was pretty well tolerated but did not by itself enhance immune responses
or clinical outcomes. The new formulation under study here (CDX-301) is produced in serum-free
medium and is expected to have similar effects but perhaps be more easily tolerated. Possible
applications for CDX-301 include boosting dendritic cell numbers for subsequent vaccinations,
modulating immune responses (increasing or decreasing them), boosting dendritic cell numbers for in
vitro studies, and increasing stem cell numbers for use in cancer therapies. The goal of the current
study is to demonstrate safety and biological activity in healthy volunteers.
If this is a clinical trial, please specify:
Intervention:
Healthy subjects will be grouped into 7 cohorts, and one cohort at a time will be treated. Subjects in
cohorts 1-5 will be treated with 5 daily doses of one dose level of CDX-301 (1, 3, 10, 25, or 75 ug/kg) by
subcutaneous injection. Thus, subjects in cohort 1 will receive 1 ug/kg daily x 5 days, while those in
cohort 5 will be treated with 75 ug/kg daily x 5 days. Cohort 6 will receive 25 ug/kg daily for 7 days, and
cohort 7 will receive 25 ug/kg daily for 10 days. Subjects will be evaluated for drug toxicity and
neutralizing anti-Flt3L antibodies.
Primary endpoint:
The primary endpoint is the safety and tolerability profile of daily CDX-301 injections at each dose level.
Secondary endpoint:
The secondary endpoints include:
1. Pharmacokinetic profiles of CDX-301 following subcutaneous injections.
2. Numbers and functions of peripheral blood hematopoietic stem cells, dendritic cells, dendritic cell
subsets, regulatory T cells, NK cells, and other blood cells.
3. Numbers and function of dendritic cells with specialized cross-presentation activity.
4. Determine the immunogenicity of CDX-301.
What are the major risks?
In previous tests, recombinant human Flt3L formulations were associated with a risk of thrombosis in
certain oncology patients who had indwelling catheters and were also treated with GM-CSF.
Lymphadenopathy and splenomegaly have been observed; these resolve after completion of treatment.
Mild to moderate injection site reactions are common.
Exacerbation of autoimmune disease has been observed in animal models and exacerbation of preexisting subclinical autoimmune disease has been reported in human trials. Subjects in the current trial
will undergo screening for rheumatoid factor and anti-nuclear antibodies; those with a positive result will
be excluded from the trial.
Because many leukemia’s express the receptor for Flt3L, subjects with a prior history of leukemia will
not be eligible for participation; there is no data suggesting that recombinant Flt3L can promote de novo
development of leukemia.
Another risk is the possibility that volunteers may develop antibody responses to Flt3L, which could
affect the activity of endogenous Flt3L.
Statistical Analysis (optional: comments in addition to Biostatistician review)
None
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What is the potential significance of the study?
A similar Flt3L preparation was tested in humans about 10 years ago, but development was stopped.
Evaluation of the earlier trials did not show strong benefits from the drug. However, the investigators
hope to benefit from current knowledge and newer experimental techniques in this study. There is hope
that the dendritic cell subsets expanded in Flt3L-treated subjects may include a subset that is active in
cross-presenting antigen to CD8+ T cells. Additionally, knowledge gained since the earlier trials may
facilitate development of methods to target dendritic cell activation and differentiation for support of
desired immune responses (for example, enhancing development of specific helper or cytotoxic T cells,
or enhancing development of regulatory T cells).
This trial may benefit from new techniques in multiplex analyses of cell phenotype and gene expression
that were not available in the earlier trials. This trial may set the stage for future trials using
combinations of cytokines to enhance desired immune responses.
Ratings:
Scientific Merit:
Priority:
Resource Intensity:
High
High
High
Recommendation
Reviewer's Recommendation of Submission
Approve with stipulations
Reviewer's Comments
The Celldex protocol states that patients "may be required to stay on the inpatient unit of the [RU]
hospital" on days of drug administration (page 31, middle paragraph). The protocol should state what
the criteria are for inpatient vs. outpatient administration of the study drug.
On page 47 of the Celldex therapeutics protocol, under "Expected Outcomes", the paragraph headed
"Human Candidate subset" is very hard to follow. This paragraph should be revised for clarity.
Indication of Review Completion
Yes
Date the Review was completed: 07/18/2011
Action: Approved w/ Concerns
Sean Brady
SBR-0752 - Metagenomic Analysis of
Natural Product Pathways in the Intestinal
Microbiome
[Reviewer: Michelle Lowes]
Scientific Initial Review
What are the background and goals of study?
This is a pilot study of 10 patients to study the gut microbiome of healthy intestine and those with
inflammatory bowel disease, analyzing samples of stool collected at Mt Sinai by collaborating
investigator Dr Bruce Sands, and sent to Dr Brady at RU
Patients over 18,
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If this is a clinical trial, please specify:
Intervention: Nil
Primary endpoint: composition of fecal microbiota
Secondary endpoint: nil
What are the major risks?
Stool collection only- minimal risk
Statistical Analysis (optional: comments in addition to Biostatistician review)
Nil proposed
The Data Analysis section states "This is purely an investigational study and no preplanned statistical
analysis is required". I believe this is not adequate. The metagenomic study will generate plenty of data
that will probably be mined and analyzed using bioinformatics tools and software. Those should be
described in this section
What is the potential significance of the study?
This study could yield interesting data on intestinal microbiome in health and disease.
Ratings:
Scientific Merit:
Priority:
Resource Intensity:
Moderate
Moderate
Low
Recommendation
Reviewer's Recommendation of Submission
Approve with recommendations
Reviewer's Comments
Please clarify the sample size- is this 10 patients over the whole study, including those with disease in
various stages and healthy volunteers?
A sample size calculation and general data analysis plan should be possible using other studies on the
microbiome.
Consent from Mt Sinai would be helpful to review that the patients are aware and approve of the
collaboration.
Indication of Review Completion
Yes Date the Review was completed: 07/13/2011
Action: Approved w/ Recommendations
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Barbara O'Sullivan
Decreasing protocol deviations through
process redesign
[Reviewer: Emil C Gotschlich]
Scientific Initial Review
What are the background and goals of study?
Adapted from the description by the PI.
In this proposal, protocol deviations reported to the IRB since 2008 will be examined to develop a
classification system of protocol deviations and to identify categories of deviations that may be
amenable to prevention by re-designing hospital processes. The study will then monitor protocol
deviations going forward in time to measure the impact of any process redesign activities.
The Hypothesis is that a systematic evaluation of protocol deviations can be used to redesign
processes that decrease the incidence of protocol deviations, thereby enhancing the safety of research
participants and the integrity of the science.
The PI will access protocol deviation reports via the electronic protocol management system. Deviation
reports that were not submitted by this system will be reviewed by the PI in a form provided by the IRB
administrative staff. The deviations will be classified as indicated in the Aims Section.
The classification scheme building will mimic that used for examining medication use. The first
classification will be based on the steps in the research process. The categories will be further refined,
and expanded as the reports are examined, to provide meaningful discrimination between types of
events.
The PI will lead root cause analyses of specific events using the expertise of the hospital staff involved
in the event. The hospital management staff has extensive experience in the conduct of root cause
analyses since this analysis is an annual requirement of Joint Commission accreditation. Process
improvement projects will be implemented by the appropriate hospital leaders in the relevant
departments.
If this is a clinical trial, please specify:
Intervention: None
Primary endpoint:
The primary aim is to review all protocol deviations and violations reported to the RU IRB since 2008
and classify them by a number of characteristics, including where in the research process they
occurred (e.g. enrollment, consent, scheduling, or specimen collection), demographics of the study
subject involved, where in the hospital the deviation occurred (inpatient, outpatient, day patient units),
what hospital departments were involved (e.g. nursing, HIS, Bionutrition, pharmacy). The classification
scheme will be revised as the events are examined.
Secondary endpoint:
Secondary aim #1. Protocol deviation categories identified as involving hospital processes will be
chosen as a subject for process redesign, or a process improvement project. As the redesign is
implemented, the data on deviation occurrence will continue to be collected. This will provide incidence
data over time that may reflect the impact of the process redesign.
Secondary aim #2. Once the retrospective data analysis yields a classification scheme (primary aim),
the data will then be collected prospectively, for an indefinite period of time, similar to the hospital's
ongoing collection of medication use variance data. As stated above (secondary aim #1), this
prospective data set will provide metrics to measure the impact of any intervention. It will also provide a
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way to examine the impact of events that occurred outside of formal process improvement activities.
For example, changes in administration, budgets, or facilities, may have a measurable impact on the
error-free conduct of research.
What are the major risks?
Loss of confidentiality inherent in any electronic system
Statistical Analysis (optional: comments in addition to Biostatistician review)
What is the potential significance of the study?
This study enhances the value of the protocol deviation/violation reports by submitting them to a
multidisciplinary scrutiny and thereby may point to processes that can be improved.
Ratings:
Scientific Merit:
Priority:
Resource Intensity:
Moderate
Moderate
Low
Recommendation
Reviewer's Recommendation of Submission
Approve
Reviewer's Comments
Indication of Review Completion
Yes
Date the Review was completed: 07/15/2011
Action: Approved
Tobias Reichenbach
TRE-0748 - The Role of Phase Information
in Frequency Discrimination
[Reviewer: Emil C Gotschlich]
Scientific Initial Review
What are the background and goals of study?
Adapted from the description by the PI.
A pure tone consists of a single frequency. We can distinguish two pure sounds if their frequencies
differ by 0.2% or even less. This separation is much less than a semitone-a step between adjacent
piano keys-which represents about 6% in frequency. We wish to study how this extraordinary frequency
discrimination is achieved.
When stimulated by a pure tone at a frequency below 300 Hz, a nerve fiber may fire an action potential
at every cycle of stimulation. Moreover, the position within that cycle (phase) at which the action
potential occurs is the same from cycle to cycle. This behavior can provide information to the brain
about the frequency of the sound. When the frequency of the sound lies between 300 Hz and 4,000 Hz,
7
a nerve fiber can no longer respond to every cycle. The responses still occur, however, at a preferred
position within a cycle. This information may help us to distinguish between different frequencies.
In our study we wish to learn whether the phase information described above helps us to discriminate
between tones of different frequencies. We will generate tones in which the phase varies. These tones
will be presented to subjects who perform a task of frequency discrimination: after listening to two tones
which differ by a certain amount in their frequency, each subject will choose which of the two tones has
the higher frequency. As a control, the subject will perform the same task with pure tones without phase
shift. This test will be conducted at different frequencies below and above 4 kHz.
Our hypothesis is that the phase-varying tones will yield a higher frequency-discrimination threshold
than the tones without phase variation when the frequency is below 4 kHz. Above 4 kHz, however, we
do not expect to see a difference in the frequency-discrimination threshold between the two types of
tones.
We also plan to vary the length of the tones and investigate to what extent short tones lead to higher
frequency-discrimination thresholds than long tones. Our hypothesis is that below 4 kHz increased tone
duration will significantly reduce the frequency-discrimination threshold because longer tones permit
better averaging and thereby more accurate assessment of phase information. For pure tones above 4
kHz we expect no strong dependence of the frequency-discrimination threshold on tone duration.
If this is a clinical trial, please specify:
Intervention:
The aims of the study are
1. Determine the influence of phase variation in pure sounds on the threshold for frequency
discrimination in different subjects.
2. Determine the influence of the length of a pure sound on the threshold for frequency discrimination in
different subjects.
The study will involve individuals with at least three years of training on a musical instrument or singing
and will be carried out in a sound proof room in Bronk Hall that has been used before for acoustic
studies on human beings.
Primary endpoint:
Assessment of the threshold for frequency discrimination relative to the average frequency, in percent
Secondary endpoint: none
What are the major risks?
Boredom, claustrophobia
Statistical Analysis (optional: comments in addition to Biostatistician review)
My main concern with this protocol is the sample size of n=1. The investigators offer no explanation of
why they will only enroll one patient. Since the test is low risk, low monetary or lab resources it is
unclear what prevent the inclusion of more than one subject. It is puzzling why they will devise the test
and the computer program with the sole purpose of including one subject. Furthermore, the aims
specifically pertain to different subjects: "Determine the influence of phase variation in pure sounds on
the threshold for frequency discrimination in different subjects". In my humble opinion the
measurements they are trying to ascertain can greatly varied across individuals.
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What is the potential significance of the study?
A clearer understanding of auditory perception
Ratings:
Scientific Merit:
Priority:
Resource Intensity:
High
High
Low
Recommendation
Reviewer's Recommendation of Submission
Approve
Reviewer's Comments
Indication of Review Completion
Yes
Date the Review was completed: 07/20/2011
Action: Approved w/ Recommendations
Jonathan Tobin
JTO-0749 - Community Acquired Methicillin
Resistant Staphylococcus Aureus (CAMP)
Project
[Reviewer: Lisa Hudgins]
Scientific Initial Review
What are the background and goals of study?
New protocol funded by the CCTS Supplemental Grant that proposes to join Community Health
Centers, Clinical Directors Network and Rockefeller and develop the infrastructure to study CAMRSA.
The aims will be
1. To assess the need for education and research in the diagnosis, treatment and prevention of
CAMRSA
2. To collect data, including 10 questionnaires, to know the number of infections, the clinical
presentation, and molecular features.
3. Develop best methods for wound culture
4. Develop a data collection system with EMR interface and ontology based on the bleeding history
project.
5. Goal is a management algorithm for clinicians
Six community health centers will enroll on site, not at Rockefeller, 129 subjects age 7-70 suspected to
have MRSA and fluent in English or Spanish recruited over 2 years. No consent or HIPPA to review.
Only exclusion criteria are inability to consent. Only risk is potential loss of confidentiality.
Compensation of up to $75.
Procedures include medical hx, physical exam including photos and culture, follow-up at 4 wk by phone
interview to check clinical response and compliance with antibiotic rx, email or text of photo of lesion by
patient/parent, chart review of medical notes, labs and prescriptions at 3 mo.
9
If this is a clinical trial, please specify:
Intervention:
Primary endpoint:
Secondary endpoint:
What are the major risks?
Potential loss of confidentiality.
Statistical Analysis (optional: comments in addition to Biostatistician review)
Justification for sample size not given.
What is the potential significance of the study?
Because of its strong base in the community, this protocol offers the potential for a more "real world"
algorithm of management of Staph Aureus infections. The molecular genotyping of the organisms
across centers and over the course of the study may yield important surprises.
Ratings:
Scientific Merit:
Priority:
Resource Intensity:
High
High
Moderate
Recommendation
Reviewer's Recommendation of Submission
Approve with recommendations
Reviewer's Comments
1. Please include a sentence explaining the basis for the number of subjects (129).
2. Please include whether family members or school classmates who become infected by a participant
will also be enrolled, and whether there will be active surveillance and education to prevent further
infections.
Indication of Review Completion
Yes
No
Date the Review was completed: 07/21/2011
Action: Approved w/ Recommendations
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3. Continuing
Alexander Ploss
APL-0719 - Characterization of Human
Antiviral Immunity
[Reviewer: Emil C Gotschlich]
Scientific Continuing Review
Provide a brief description of the protocol:
This is a protocol to obtain blood from normal volunteers, Yellow fever vaccinated individuals and
people recovered from Dengue. The PBMCs will be isolated and used to produce mice with a
humanized immune system. These in turn will be used to study the pathogenesis and immunology of
yellow fever and dengue.
So far two normal volunteers have been studied and the use of their cells injected into NOD Rag1-/IL2RNULL (NRG) yielded high degrees of human engraftment. The mice have been infected with
yellow fever virus YF17D and the results are pending.
What was the enrollment over past year compared with the expected enrollment?
Slow because of some issues with blood drawing materials
Were there any notable adverse events?
None
What were the notable scientific findings?
Engraftment of the mice was successful.
Describe publications and presentations in the last year:
None
Describe changes in:
Protocol: minor
Resources, Utilization: unchanged
Recommendation
Reviewer's Recommendation of Submission
Approve, exempt from Review
Reviewer's Comments
Indication of Review Completion
Yes
No
Date the Review was completed: 07/20/2011
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Statistical Review:
In my previous review of this protocol, I point out the complete lack of any data analysis plan,
which is easily supported by the 4 biostatisticians working at our hospital. The sample size had
never been planned and it was and still is stated that " To ensure we have correct sample size
for the number of HIS mice to generate, we will consult online statistical calculators to perform
a power calculation test comparing two proportions (
http://www.stat.uiowa.edu/~rlenth/Power/index.html</&NBSP;FONT>).".
At this point I wonder when the investigators plan, if at all, to really conduct sample size
estimation and prepare a data plan.
Action: Approved w/ Recommendations
4. Amendment
Peter R Holt
PHO-0702 - Docosahexaenoic Acid (DHA)
Reduces Inflammation and Aromatase
Expression in Subcutaneous Fat and
Inflammation in the Rectosigmoid Mucosa in
Obese Postmenopausal Women: a Pilot
Study
[Reviewer: Lisa Hudgins]
Scientific Initial Review
What are the background and goals of study?
The hypothesis is that DHA, an omega 3 fatty acid, will reduce COX2 and PGE2-mediated inflammation
in human fat tissue and the colon and lower estrogen production by reducing aromatase activity. Five
obese postmenopausal women age 40-70 and BMI between 30 and 40 were admitted for 4 day
inpatient stays before and after 12 weeks of DHA 1 g bid open label without a placebo.
The amendment proposes
1. Addition of 12 postmenopausal women same age range but higher BMI >35 in the next year
2. Deletion of sigmoid/colon biopsies
3. Deletion of BOD POD and RRE, omission of phospholipid fatty acids from 6 wk time point,
4. Change of study contact (and supplier of DHA) from Martek to DSM
5. Change in 2 key personnel
6. Reduction in compensation from $1000 to $600.
If this is a clinical trial, please specify:
Intervention:
Primary endpoint:
Secondary endpoint:
What are the major risks?
Risks are reduced with the omission of the colon biopsy.
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Statistical Analysis (optional: comments in addition to Biostatistician review)
None of the changes to this protocol are related with experimental design, sample size and data
analysis plan.
What is the potential significance of the study?
The potential significance of the study has not substantially changed, but no preliminary data has been
presented.
Ratings:
Scientific Merit:
Priority:
Resource Intensity:
Moderate
Moderate
Moderate
Recommendation
Reviewer's Recommendation of Submission
Approve with recommendations
Reviewer's Comments
Please give the reason(s) for changing the inclusion criteria, omitting the colon biopsy, BODPOD and
REE and studying more patients. Is there any preliminary data?
Indication of Review Completion
Yes
Date the Review was completed: 07/21/2011
Action: Approved
Tobias Reichenbach
TRE-0748 - The Role of Phase Information
in Frequency Discrimination
[Reviewer: Emil C Gotschlich]
Scientific Initial Review
What are the background and goals of study?
This study has been reviewed previously by the ACCTTS. It concerns the ability to discriminate the
pitch of sounds under conditions where phase shifts are introduced into the sounds presented. Initially
the request by the PI was for one subject only to work out the logistic details. The current amendment
proposes two changes:
Increase the population to be studied to 10,
Include not only subjects with 3 years of formal training on string instruments, but also other musical
instruments or singing.
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If this is a clinical trial, please specify:
Intervention: unchanged
Primary endpoint: Unchanged
Secondary endpoint: Unchanged
What are the major risks?
Unchanged
Statistical Analysis (optional: comments in addition to Biostatistician review)
What is the potential significance of the study?
Unchanged
Ratings:
Scientific Merit:
Priority:
Resource Intensity:
High
Low
Low
Recommendation
Reviewer's Recommendation of Submission
Approve
Reviewer's Comments
Indication of Review Completion
Yes
Date the Review was completed: 07/15/2011
Action: Approved
Bryan Yipp
BYI-0736 - A Randomized, Blinded,
Placebo-Controlled Phase 1 Study to
Evaluate the Safety and Immunogenicity of
GLA in Healthy Volunteers
[Reviewer: Emil C Gotschlich]
Scientific Initial Review
What are the background and goals of study?
This study has been previously reviewed by the ACCTS and the IRB in March and approved with
enrollment pending review of the IND by the FDA. In brief this is a study of the potential adjuvant
properties of GLA a synthetic compound mimicking the core of LPS. The FDA approved this study on
May 18, 2011 with a number of suggestions. The Investigators amended their study top include these
changes and that is the action item for this review.
The detailed changes are:
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The study investigators have made the decision to remove the intradermal route from the study for the
time being, because more toxicology data is necessary before proceeding with that portion of the trial.
These toxicology studies will be performed this fall, and the study may be amended to add the
intradermal route once more supporting data has been collected. The following changes have been
made to that effect:
Section 6.0 has been amended to remove mention of the intradermal route.
Section 7.11 has been changed to answer "No" to the question "Are there devices to be used in the
study?"
Section 8.1, subheading GLA Background Information has been amended to remove mention of the
intradermal route and removal of the following paragraph, "A device developed by NanoPass
Technologies Ltd. will be used for intradermal injections. The Micron Jet 600 is a small plastic device
equipped with 3 microneedles, each 600 micrometers (0.6mm) in length that provides means of
controlled and standardized intradermal injections. This device was found to be equivalent to predicate
devices and a 510(k) (# K092746) was approved February 3 2010 for marketing and use as an
intradermal drug administration device."
Section 8.1, subheading Summary has been modified to remove mention of the intradermal route.
Section 8.2 has been modified to remove mention of the intradermal route.
Section 8.3 has been modified to remove mention of the intradermal route.
The first paragraph of Section 8.6 has been modified to remove mention of the intradermal route and
the Micronjet device. In addition, the total number of subjects has been changed to 32 from 48. All 16
volunteers to be enrolled in the intradermal route have been removed.
Section 8.6, subheading Administration Visit (Day 0), bullet 9, mention of the intradermal route has
been removed.
Section 8.6, subheading Randomization and Blinding has been modified to remove mention of the
intradermal route and the Micronjet device.
Section 8.6, subheading External Parties has been modified to remove mention of the intradermal
Micronjet device.
Section 8.8 has been modified to remove mention of Cohort III and the intradermal route. In addition,
the total number of subjects has been changed to 32 from 48, and the over enrollment has been
changed to 3 volunteers from 5 volunteers.
Section 9.3 has been changed to reflect a total number of subjects of 32 rather than 48.
Section 9.6 has been modified to allow for 3 Rockefeller employees as volunteers rather than 5.
Sections 9.7 and 9.8 have been changed to answer "32" rather than "48" volunteers.
Sections 9.9 and 9.10 have been changed to answer "64" rather than "96" volunteers.
Section 10.0 has been modified to read 192 in answer to the question "What is the total number of
outpatient visits for all subjects projected for the next year?" rather than 288.
Section 16.0 has been modified to remove mention of the intradermal route.
Section 17.0, the first bullet, has been modified to reflect a total number of subjects of 32 rather than
48. In addition, it has been updated to indicate that the first 14 subjects in each cohort will be injected
with the study drug at least one day apart rather than 13. Finally, mention of cohort III was removed in
this section.
The Informed Consent Form, third paragraph, has been changed to reflect a total number of subjects of
32 rather than 48.
The Informed Consent Form, subheading Study Participation, bullet three has been changed to remove
mention of the intradermal route.
The CCTS was amended to reflect the changes made to the new total number of volunteers, 32.
The following changes have also been made, which were separate from the removal of the intradermal
route:
Section 5.0 has been amended to add the responsibilities "3. Medical/Medication History" and "4.
Perform physical exam" to the Study Co-Investigator Arlene Hurley. The responsibility "10. Administer
study questionnaire(s)" was added to the Study Co-Investigators Bryan Yipp, Marina Caskey, Sarah
Schlesinger, Niroshana Anandasabapathy, Sarah Pollak, Arlene Hurley, and Saurabh Mehandru.
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In Section 8.6, a subheading "Follow-Up Phone Calls" was added and includes the following text:
"Study staff will call volunteers at 3 months, 6 months, and 1 year post injection. During the phone call,
study volunteers will be asked about their general health status since the last visit. Volunteers will be
specifically prompted as to whether they have had any new diagnoses since the last contact. The
phone interview will be performed according to a script (see Follow-Up Questionnaire). Additional study
visits may be scheduled if advised by the study investigator. Volunteers who have developed a health
problem will be referred to appropriate medical care by the study team or the RUH social worker."
In Section 8.9, the following sentence was added to the first paragraph "Study analysis will be
performed based on the 28 day study visit schedule, but volunteers will be monitored using phone calls
per the recommendations of the FDA."
Section 20.0 was amended to include the following sentence at the suggestion of the FDA, "The trial
will also be stopped if a DLT is reached by three individual volunteers."
The second paragraph was modified to read: "A dose limiting toxicity (DLT) will be defined as any
clinical sign or symptom of Grade 3 or higher, including a fever greater than or equal to 40°C and grade
4 erythema at injection site, if the study investigators recognize a possible or definite attribution to the
study drug."
The Schedule of Procedures has been updated to include the three Follow-Up Phone Calls.
The Informed Consent Form, subheading Study Participation, bullet 8 was added and includes the
following text: "You will be called by the study investigators 3 months, 6 months, and 12 months after
the injection for a short follow-up questionnaire."
A Follow-Up Questionnaire was added for the follow-up phone calls.
A letter from the FDA detailing their recommendations was attached to this amendment form.
If this is a clinical trial, please specify:
Intervention: unchanged
Primary endpoint: unchanged
Secondary endpoint: unchanged
What are the major risks?
Unchanged
Statistical Analysis (optional: comments in addition to Biostatistician review)
What is the potential significance of the study?
Unchanged
Ratings:
Scientific Merit:
Priority:
Resource Intensity:
High
High
High
Recommendation
Reviewer's Recommendation of Submission
Approve
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Reviewer's Comments
Indication of Review Completion
Yes
Date the Review was completed: 07/15/2011
Action: Approved
5. Others Submissions
Ronald Crystal
RCR-4440 - Evaluation of the Lungs of
Individuals with Lung Disease with
Segmental Bronchopulmonary Lung
Lavage, Bronchial Brushing, and Bronchial
Wall Biopsy
[Reviewer: Michelle Lowes]
Scientific Initial Review
What are the background and goals of study?
This is an amendment to an IRB-approved general tissue collecting protocol from the Crystal Lab at
WMC. The Crystal lab studies pulmonary diseases, and conducts bronchoscopy and possible bronchial
brushings, lavage, and biopsy either as part of routine clinical care (Group A), or for research purposes
(Group B), at WMC. Other investigations are also conducted at WMC. Rockefeller University and New
York Pulmonary Associates have been added as additional sites. Bronchoscopy, blood draw, CXR and
echocardiograph may be performed at Rockefeller University.
This amendment is for the following:
1. Change in radiation dosage for CT scans
2. Modified consent to include additional side effects of the fiber optic bronchoscopy
procedure/anesthesia- disorientation and increased mucus production
3. Additional compensation of $25 for Group B subjects completing the methacholine challenge test
4. An information sheet has been added for stamping regarding patients withholding asthma
medications
If this is a clinical trial, please specify:
Intervention: N/A
Primary endpoint: N/A
Secondary endpoint:
What are the major risks?
Additional risks of bronchoscopy added- increased mucus production and disorientation
Statistical Analysis (optional: comments in addition to Biostatistician review)
N/A for amendment
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What is the potential significance of the study?
This protocol presents a good opportunity to acquire specimens and data to study pulmonary diseases
Ratings:
Scientific Merit:
Priority:
Resource Intensity:
Moderate
Moderate
High
Recommendation
Reviewer's Recommendation of Submission
Approve
Reviewer's Comments
Indication of Review Completion
Yes
Date the Review was completed: 07/18/2011
Action: Approved
6. Exempt Protocols
Agata Smogorzewska
ASM-0751 - DNA damage response (DDR)
in nephronophthisis-related ciliopathies and
karyomegalic interstitial nephritis
[Reviewer: Martin Markowitz]
Δ Exempted by reviewer
Ira Jacobson
IJA-1002010862 - Abbott M11-602: A
Blinded, Randomized, Placebo-controlled,
Dose Ranging Study to Evaluate the Safety,
Tolerability, Pharmacokinetics, and Antiviral
Activity of Multiple Doses of ABT-450 with
Ritonavir (ABT-450/r), ABT-333 or ABT-072
Each Administered Alone and in
Combination with Peginterferon --2a and
Ribavirin (PegIFN/RBV) in TreatmentNaive Subjects with Genotype 1 Chronic
Hepatitis C Virus (HCV).
[Reviewer: Edgar Charles]
Δ Exempted by reviewer
Manish Ponda
MAP-0683 - The Effect of Vitamin D3
Repletion on Small LDL Particle Number in
Subjects at Elevated Cardiovascular Risk
[Reviewer: Edgar Charles]
Δ Exempted by reviewer
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Robert B Darnell
RDA-0611 - A phase I study of autologous
dendritic cells pulsed with autologous
apoptotic tumor cells (DC/AAT)
administered intradermally to cancer
patients with brain tumors
[Reviewer: Edgar Charles]
Δ Exempted by reviewer
Ana Krieger
AKR-0102 - Mechanisms of Endothelial Cell
Dysfunction in Sleep Apnea
[Reviewer: Emil C Gotschlich]
Δ Exempted by reviewer
Jasimuddin Ahamed
JAH-0715 - Activation of Platelet-Derived
Transforming Growth Factor-ß1 (TGF-ß1) in
Diseases where High Shear Force is
Involved, Including in Aortic Stenosis, Sickle
Cell Anemia/ß-Thalassemia, Systemic
Sclerosis, LVAD Implantation, and During
Platelet Storage.
Manu N Capoor
MCA-0669 - Surgical Stratification and
Surveillance System
JCA-0640 - Human Genetics of Infectious
Diseases
Jean-Laurent Casanova
Jean-Laurent Casanova
JCA-0678 - Molluscum Contagiosum in
Childhood: a Novel Primary
Immunodeficiency?
Jean-Laurent Casanova
JCA-0699 - Genetic Predisposition to
Mycobacterial Diseases
Jean-Laurent Casanova
JCA-0695 - Genetic Predisposition to
Infectious Diseases
Marina F Caskey
MCA-0718 - An open label study to evaluate
innate immune responses induced by a
pattern recognition receptor agonist, polyICLC (Hiltonol), in healthy volunteers
Barry S Coller
AMA-0637 - Assessment of Bleeding
Symptoms in Normal Individuals Using a
Comprehensive Bleeding History
Phenotyping Instrument
Barry S Coller
BCO-0417 - Studies of: 1. normal and
abnormal blood cells, 2. genetic disorders of
blood cells and coagulation factors, and 3.
transforming growth factor-ß1 in health and
disease: PATIENTS AND FAMILY
MEMBERS
19
Barry S Coller
BCO-0726 - Studies of: 1. normal and
abnormal blood cells, 2. genetic disorders of
blood cells and coagulation factors, and 3.
transforming growth factor-ß1 in health and
disease: NORMALS
Ronald Crystal
RCR-4439 - Evaluation of the Lungs of
Normal (Smokers, Ex-smokers, Nonsmokers)Individuals with Segmental
Bronchopulmonary Lung Lavage, Bronchial
Brushing and Endobronchial Wall Biopsy
Ronald Crystal
RCR-0391- The Natural History of Gene
Expression in Lung Cells of Non-Smokers,
Smokers, and Ex-Smokers in Health and
Disease
Lindsay Dick
LDI-0731- Pilot Study: Isolation of Cues that
Drive Mosquito Preference for Certain
Human Hosts
Lynn Dustin
LDU-0437 - Hepatitis C Virus and the
Humoral Immune System (Expedited)
Winrich Freiwald
WFR-0741 - The Neural Basis of Face
Recognition and Social Cognition: A
Magnetic Resonance Imaging Study
Winrich Freiwald
WFR-0730 - The Capture of Attention: A
Magnetic Resonance Imaging Study
Charles Gilbert
CGI-0121 - Processing Mechanisms in
Visual Cortex
Peter Holt
SWP-0620 - Obesity associated Colorectal
inflammation; the effects of weight loss
Florian Klein
MNU-0625 - Identification and
Characterization of Human Auto-Reactive B
Cells in Autoimmune Diseases, HIV
Infection and Healthy Volunteers
Florian Klein
MNU-0628 - Leukapheresis Procedure and
Bone Marrow Aspiration for the
Identification and Characterization of
Human Auto Reactive B Cells in
Autoimmune Diseases, HIV Infection and
Healthy Volunteers
James Krueger
JKR-0723 - Randomized, Double-Blinded,
Placebo-Controlled Parallel-Design doseRange Finding Study of Subcutaneous SCH
900222 in Subjects with Moderate-to20
Severe Chronic Plaque Psoriasis
James Krueger
JKR-0397 - Collection of Blood Specimens
for Research Purposes
James Krueger
JKR-0671 - A Randomized, Double-blind,
Placebo-controlled, Ascending Dose Study
to Assess the Safety, Tolerability,
Pharmacokinetics, and Pharmacodynamics
of CNTO 1959 following a Single
Intravenous or a Single Subcutaneous
Administration in Healthy Subjects and in
Subjects with Moderate to Severe Psoriasis
James Krueger
JKR-0638 - Effects of narrowband UVB
phototherapy on melanocyte proliferation in
patients with vitiligo (No participant accrualonly open for data analysis)
James Krueger
JKR-0746 - A Phase 3, multi-site, openlabel study of the long term safety and
tolerability of 2 oral doses of CP-690,550 in
subjects with moderate to severe chronic
plaque psoriasis
Protocol Number: A3921061
Martin Markowitz
MMA-0639 - Acute HIV-1 Infection
Prospective Cohort Study (CHAVI-001)
Jurg Ott
JOT-0632 - Genetic Susceptibility in
Recurrent Respiratory Papillomatosis
Studying RNA Regulation in Diseased
Tissues Obtained from Established Tissue
Banks
Neil Renwick
Peter Schlegel
PSC-0633 - A three-part trial assessing the
effects of 7 alpha-methyl-19-nortestosterone
(MENT) on blood pressure in normal men:
an open-label pilot study, a nested
pharmacokinetic study, followed by a
randomized, double-blind, placebocontrolled study
Sarah Schlesinger
SSC-0605 - A Single-Patient Study Using
AGS-006 as an Immunotherapeutic in a
Subject with Newly Diagnosed Resectable
Pancreatic Cancer
Sarah Schlesinger
SSC-0710 - A randomized, placebocontrolled, dose-escalating, double-blinded
phase 1 study to evaluate safety and
immunogenicity of anti-DEC-205
monoclonal antibody (mab) targeted HIV
21
gag p24 vaccine (DCVax-001) with poly
ICLC (Hiltonol) as adjuvant in HIVuninfected healthy volunteers
Sanford Simon
SSI-0624 - Imaging Single Molecular Events
in the Cell
Thomas Tuschl
TTU-0707 - Collaborative Approaches to
Characterizing Post-Transcriptional
Regulation of Gene Expression in Health
and Disease
Leslie Vosshall
LVO-0619 - Physiological Effects of
Androstadienone Exposure
Shen-Ying Zhang
SHZ-0676 - Mendelian Genetic
Predisposition to Herpes Simplex
Encephalitis in Childhood
7. Reports of Director and Co-Director
Dr. Coller reported that the advisory committee for the NCATs met the previous week, but to date there
has been no update on when (or if) NCATS will be created.
Dr. Coller noted that he had requested the help of the REPPS to aid in planning the Center retreat.
Dr. Coller announced that the Therapeutic Discovery and Development Interest Group will meet the first
Tuesday in August.
8. Reports of Subcommittees
A) Research Education Training and Career Development Subcommittee (Sarah Schlesinger)
Dr. Schlesinger announced that the new Clinical Scholars have started.
9. Review of Center Metrics and Resource Utilization
10. Assessment of Underutilization, Inappropriate Use, and Low Productivity
11. Review of Budget
12. Strategic Planning Issues
The meeting was adjourned at 4:17 pm
Respectfully submitted,
_________________________________
Maija Williams, MPH
ACCTS Administrator
_________________________________
Robert B. Darnell, MD, PhD
Chair
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