Download ICRF Phase I Additional Information - Imperial CRF

Study Number
Study Acronym
Protocol Version
NIHR/Wellcome Trust Imperial CRF
Phase I Additional Information Form
Study Title:
FIH study?
Select
Dose escalation study?
Select
Principal Investigator:
Researcher(s) conducting study:
Sponsor:
Protocol version:
Number of IMPs
Refer to guidance in ‘Guideline on Strategies to Identify and Mitigate Risks for First-In-Human Clinical Trials with Investigational
Medicinal Products’ EMEA 2007
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1. Study Team
1.1
Principal Investigator
The cv of the PI must clearly identify the qualifications, experience and key publications in support of the role as PI
for this study. Provide only concise, relevant information.
1.1.1 Clinical Pharmacology qualifications and experience of PI
Phase I application previously submitted to the PRB with this PI? Select If yes, move to section 1.2 unless details have
changed
On MHRA Approved List for PIs for FIH trials / Phase 1 for relevant IMP? Select If yes, move to section 1.2
CCT in clinical pharmacology & therapeutics Select Year obtained
CCT in pharmaceutical medicine
Select Year obtained
PhD in clinical pharmacology
Select Year obtained
Clinical pharmacology experience:
Industry experience
Select No. Years
Academic experience
Select No. Years
ICRF-OR09 Form 4 v4 Imperial CRF Phase I Additional Information Form March 2015
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Study Number
Study Acronym
Protocol Version
1.1.2 Research experience of PI
Experience of Experimental Medicine studies or CTIMP studies in last 3 years? Select No. of studies and role:
Experience of Phase I trials: Select No. of trials and role:
Experience of FIH trials:
Select No. of trials and role:
Experience of studies with dose escalation: Select No. of trials and role:
Please provide details below of this Phase I/FIH/dose escalation experience. Include any relevant publications:
1.1.3 Role and competence of the PI
What clinical functions will the PI perform in this study (eg administration of drug, mentoring, clinical input etc)?
1.1.4 PI clinical pharmacology advice for FIH studies (if required for role of PI)
What CP input does the PI require (eg review pre-clinical data, assess the pharmacology and subsequent aspects
such as the proposed starting dose, dose escalation proposal/stopping criteria etc)?
1.1.5 Training status of PI
GCP trained
Select Date of training: Click here to enter a date. Training provider:
ALS trained
Select Date of training: Click here to enter a date. Training provider:
Please provide details of other training/ skills essential for the PI for this study:
1.2 Researchers conducting the study
Please provide information for the main researchers (other than PI).
Copy and paste additional section 1.2 for more than one researcher (see guidance above)
Name of researcher:
Phase I application previously submitted to the PRB with this researcher? Select If yes, move to section 2.1 unless
details have changed
1.2.1 Qualifications of researcher:
State relevant qualifications and training (including pharmacology):
1.2.2 Research experience of researcher:
State FIH, Phase I or relevant experience:
1.2.3 Supervision of researcher
Name of supervisor for the researcher(s) if not the PI:
What supervision will be provided?
1.2.4 Training status of researcher
GCP trained
Select
Date of training: Click here to enter a date. Training provider:
ALS trained
Select
Date of training: Click here to enter a date. Training provider:
Please provide details of other training/ skills essential for the research for this study:
2. Pre-clinical development data (provide information for each IMP)
Number of IMPs for this study:
please complete for each IMP. Use additional section 2 if more than 1 IMP (see
guidance above)
Name of IMP:
Use additional section 2 if more than 1 IMP
ICRF-OR09 Form 4 v4 Imperial CRF Phase I Additional Information Form March 2015
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Study Number
Study Acronym
Protocol Version
2.1 Is there evidence of previous exposure of humans to compounds with related modes of action? Select
Provide details:
2.2 Is there evidence from animal models for potential risk of serious pharmacologically mediated toxicity? Select
Provide details:
2.3 What animal species have been studied? (see also 3.3)
2.4 Provide evidence of a risk analysis of the pre-clinical data for the IMP(s) including:
2.4.1 Identification of the on-target and off-target areas of the IMP:
2.4.2 The adverse events associated with the on-target and off-target areas:
3. Investigational Medicinal Product (provide information for each IMP)
Name of IMP
Use additional section 3 if more than 1 IMP (see guidance above)
3.1 Mode of action:
Novel molecular structure:
Biological cascade/ cytokine release:
Multiple signalling pathways:
Select
Select
Select
3.2 Nature of target:
Provide available knowledge on the nature of the target and variation between individuals:
3.3 Relevance of animal species and models
Justify the use of the model used, ensuring evidence of comparison of available animal species to humans (in
support of 2.3) :
3.4 CT(EAG) review:
Does this study have risk factors requiring review by the Expert Advisory Group (EAG) to the Committee on Human
Medicines (CHM)? Select
4. Administration of doses (provide information for each IMP)
Name of IMP
Use additional section 4 if more than 1 IMP (see guidance above)
Drug Administration
4.1 What is the route of administration?
4.2 What is the rate of administration?
Dose Calculation
4.3 What is the estimation of first dose?
4.4 What method was used to calculate the dose?
4.5 Who will be responsible for checking the calculations at dosing time?
Drug Exposure
4.6 What is the expected total exposure of the associated drug and the anticipated plasma concentrations?
4.7 How do these values compare with the exposure and achieved concentrations in the animal models previously
studied?
Dose Escalation Plan
ICRF-OR09 Form 4 v4 Imperial CRF Phase I Additional Information Form March 2015
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Study Number
Study Acronym
Protocol Version
4.8 What is the dose escalation plan (if applicable)? Include details of the number of subjects required to make a
dose escalation decision (dose cohort) and the time interval required before proceeding to a new dose and / or new
subject
4.9 What is the justification for the dose escalation plan adopted?
Staffing
4.10 Who will administer the first dose? (eg PI/ researcher/nurse)
4.11 Which members of the study team will be present at the administration of first dose?
4.12 CRF Nursing staff level requested per subject:
Medical Staff Cover
4.13 What medical cover will be in place for the first administration of the IMP in the first patient at this site?
Name:
Duration of cover:
Locality of cover (e.g. in CRF, at HH etc):
4.14 What medical cover will be in place for first administration of the IMP in subsequent patient?
Name:
Duration of cover:
Locality of cover (e.g. in CRF, at HH etc):
4.15 What medical cover will be in place for the subsequent doses?
Name:
Duration of cover:
Locality of cover (e.g. in CRF, at HH etc):
Dosing intervals
4.16 What is the time period between administrations of IMP to subsequent subjects within the cohort? (Justify this
decision)
4.17 What is the time period between the first and subsequent doses in the first subject? (Justify this decision)
5. Statistics
Please ensure that appropriate statistical advice has been sought. The Committee will review the statistical aspects
of the study from the protocol and ethics form submitted. Provide any additional, relevant information below.
6. Adverse reactions (account for each IMP)
Name of IMP
Use additional section 6 if more than 1 IMP (see guidance above)
6.1 Describe the measures in place to monitor key on-target and off-target areas as identified in 2.4.1, including the
additional tests to be undertaken to monitor for possible off-target effects (eg bp, glucose, liver toxicity etc).
6.2 Describe the strategy to manage likely adverse events or adverse reactions as identified in 2.4.2.
6.7 Will an antidote be immediately available on site? : Select
If no, justify and detail contingency plan.
If yes, provide details of the antidote and plan for subject management:
6.4 Detail AE reporting system to be used:
ICRF-OR09 Form 4 v4 Imperial CRF Phase I Additional Information Form March 2015
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Study Number
Study Acronym
Protocol Version
6.5 Describe the procedures for emergency unblinding of study drugs:
6.3 List expected notable adverse events. Details should be included in the Clinical Risk Assessment and
Management Plan
7. Suitability of subjects
The requirement for confirmation of a subjects’ past medical history (PMH) will be risk assessed. Where required this
should be obtained via the subjects’ GP or other medic such as a hospital consultant for patient studies, to provide
assurance that inclusion and exclusion criteria are met.
7.1 Describe how subjects’ past medical history will be obtained:
7.2 If the patients PMH will not be obtained from the GP, justify this decision:
7.3 Justify choice of subjects for this study:
7.4 Give clear guidance on what constitutes a valid subject.
7.5 Do inclusion/ exclusion criteria take account of possible allergic response to planned antidotes or treatment of
AEs? Select
8. Pharmacy information
Name of IMP
Use additional section 8 if more than 1 IMP (see guidance above)
8.1 Source of IMP(s)
Name of company providing IMP:
Is the company within the EU? Select
If not within EU please state where located and the company providing EU QP release:
Is availability guaranteed for the duration of the study?
Provide QP and TSE certification for manufacture and further manipulation or processing:
8.2 Dispensing/ Compounding
Does the IMP require further compounding and/or assembly by pharmacy, and if so what? Select
If yes, will doses be required to be ready outside of Mon-Fri 10.30am-5pm?
Is PK sampling required post-dose, and if so what?
8.3 Stability of the IMP(s)
What is the shelf life of the IMP?
What is the stability of the IMP once in the form in which it will be administered to patients?
8.4 Storage of the IMP(s)
What are the storage requirements for the IMP(s) eg frozen at -80C?
8.5 Reliability of very small doses
Is there a need for demonstration that the intended formulation of the doses to be administered provides the
intended dose?
9. Contingency planning and safety considerations.
Discontinuation criteria
9.1 The criteria and protocol for premature discontinuation of IMP in an individual? (This should include clear details
on clinical parameters):
ICRF-OR09 Form 4 v4 Imperial CRF Phase I Additional Information Form March 2015
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Study Number
Study Acronym
Protocol Version
9.2 The criteria for stopping the trial:
Antidotes & specific treatments
9.3 Specific instructions for antidote (if applicable):
9.4 Contingency plan for on- and off-target effects, including details of specific treatments that must be held on-site
to manage expected adverse reactions:
Specialist support
9.5 State if a relevant specialist is required to be available to support emergencies and adverse event management:
Please detail who is required and under what circumstances:
Data and safety review
9.6 Will an independent data/safety monitoring committee be set up?
9.7 Plan for data and safety review following first dose and prior to subsequent dosing:
9.8 Plan for data and safety review prior to subsequent subject recruitment:
Operational requirements
9.9 Identify proposed room allocation or specific requirements for participant observation for duration of CRF
admission:
9.10 Maximum number of subjects on any given day (after review of initial dosing studies):
9.11 Need for overnight observation? Select
9.12 Additional considerations:
ICRF-OR09 Form 4 v4 Imperial CRF Phase I Additional Information Form March 2015
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