Download A5336 A Phase Iia, Double-blind, Placebo

A5336
A Phase IIa, Double-blind, Placebo-controlled,
Randomized Trial of Ruxolitinib in
Antiretroviral-treated HIV-Infected Adults
CAB Draft Discussion
Tuesday, January 14, 2014
CWRU/UH CRS CAB Meeting
Inflammation
Anti-HIV medicines have been very successful in allowing people
with HIV to control the virus.
However, researchers have noticed that many patients have high
levels of inflammation even when their medicine is controlling their
HIV viral load.
Inflammation is the body’s response to infection or irritation that
can be helpful sometimes but can cause long-term problems when
it lasts too long.
Researchers believe that people with high levels of inflammation
could, over time, have an increased risk to develop certain health
problems such as heart disease and some forms of cancer.
Cytokines
A cytokine is a small protein released by cells that
has a specific effect on the interactions between
cells, on communications between cells or on the
behavior of cells.
Examples:
Some cytokines are chemical switches that turn certain immune cell types on and off.
For example, one cytokine, interleukin 2 (IL-2), triggers the immune system to
produce T cells.
One group of cytokines chemically attracts specific cell types. These so-called
chemokines are released by cells at a site of injury or infection and call other immune
cells to the region to help repair the damage or fight off the invader.
Schema
Design: Multi-center, phase IIa, randomized, double-blind, placebo-controlled trial.
Duration: 12 weeks. 9 visits including screening visit.
Sample size: 60 subjects on continuous ART medicine for at least 2 years, with no plans to
change medicines for duration of study. Regimen must include either TDF/FTC or ABC/3TC
plus an NNRTI or INSTI for at least two months. (At least 15 participants must be on ART
medicine efavirenz (EFV) to evaluate effect of study drug on EFV).
Population: HIV infected adults (> 18 years old) on stable ART containing either an NNRT
or integrase strand transfer inhibitor. Must have virologic suppression (at least 2 viral
loads under 50; with no viral loads greater than 50 for 12 months prior to entry. Not more
than one viral load between 50 and 200 for at least 2 years). CD4 call count 350 or higher.
Study drug: Randomized 3:1 Ruxolitinib 10 mg orally twice daily or placebo orally twice
daily for five weeks.
Ruxolinitib
Ruxolitinib is an FDA-approved medicine for the treatment of
myelofibrosis, a disorder in which bone marrow is replaced
by scar (fibrosis) tissue. Myelofibrosis can lead to leukemia.
Many of the cytokines affected by myelofibrosis are also
affected by HIV. Because ruxolitinib acts on these cytokines,
it is proposed that is may also reduce inflammation in the
bodies of people living with HIV.
Primary Objective
To evaluate the safety and tolerability of ruxolitinib
in ART-treated HIV-1 virologically suppressed
infected subjects and compare changes in IL-6
levels between subjects randomized to ruxolitinib
and those randomized to placebo, during 5 weeks
of treatment.