HIV, Inflammation Clinical Trial
Official title:
A Phase 1 Study of CC-11050 in Human Immunodeficiency Virus-1-Infected Adults With Suppressed Plasma Viremia on Antiretroviral Therapy
Background:
When there is a threat to the body, the immune system triggers inflammation. Too much
inflammation can damage the body or cause painful symptoms. Some people with HIV feel sick
after they start HIV drugs because their recovering immune systems cause too much
inflammation. Or their immune systems can become activated all the time. This can cause
serious health problems. Researchers want to test if the drug CC-11050 helps treat
inflammation in people taking HIV drugs.
Objectives:
To test if CC-11050 is safe and well-tolerated for people with HIV who are taking HIV drugs.
To see if it reduces inflammation.
Eligibility:
People ages 18 and older with HIV who have been on antiretroviral therapy for at least 1
year.
Design:
Participants will be screened with:
Medicine review
Physical exam and medical history
Blood and urine tests
Chest x-ray
Electrocardiogram (ECG): Soft electrodes on the skin record heart signals.
Participants will be randomly assigned to take capsules of either CC-11050 or a placebo. They
will take the capsules every day for 12 weeks. They will continue to take their HIV drugs.
Participants will have a baseline visit within 2 months of screening. This includes:
Physical exam and medical history
Blood and urine tests
ECG
Leukapheresis: Blood is removed by a needle in one arm and passed through a machine that
removes white blood cells. The rest of the blood is returned through a needle in the other
arm.
Participants will have follow-up visits 2, 4, 8, 12, and 16 weeks after the baseline visit.
These may include repeats of some of the baseline tests.
CC-11050 is a novel anti-inflammatory compound with potential to treat a variety of chronic
inflammatory conditions and cytokine storms associated with infectious diseases. CC-11050 is
a selective phosphodiesterase-4 inhibitor (PDE4) that is active in several in vivo models of
inflammatory disease, inhibiting systemic TNF- production, colitis symptoms of the colon,
psoriasiform features in the skin, arthritogenic swelling in the joints, neutrophilia and
eosinophilia in the lung, and reducing choroidal neovascularization. These data suggest that
CC-11050 may have therapeutic potential for chronic inflammatory conditions and/or as an
antiangiogenic treatment. The safety profile of CC-11050 has been investigated in healthy
males and in subjects with cutaneous lupus erythematosus; the most frequently reported
adverse events were fatigue, headache, upper respiratory infection and pruritus; there were
no deaths or serious adverse events.
Inflammation is an important contributor to HIV pathogenesis both prior to and after ART
initiation. Inflammatory responses can occur abruptly upon ART initiation (known as immune
reconstitution inflammatory syndrome or IRIS) and can be chronic in persons with suppressed
plasma HIV viremia who are treated with ART, and has been linked to an excess risk of
non-AIDS serious events such as cardiovascular, liver and kidney disease and accelerated bone
loss. Corticosteroids to reduce levels of inflammatory cytokines in plasma are a standard
therapeutic intervention for IRIS, however a more targeted anti-inflammatory and less broadly
immunosuppressive intervention is desirable.
We propose a double-blind, randomized trial to assess the safety of CC-11050 in adults with
HIV infection who have taken ART for at least 1 year and have suppressed plasma viremia.
Enrolled subjects will be randomized 2:1 to 200 mg CC-11050 or placebo twice daily for 12
weeks. Participants will be evaluated at weeks 0, 2, 4, 8, 12 and 16. Changes in in plasma
HIV-1 RNA levels (by clinical assay), CD4+ T cell counts and percentages, and the effect on
markers of systemic inflammation (e.g., TNF, IL-6, CRP, IFNg, sCD14, D-dimer) will be
measured. The effect of CC-11050 on cellular immune activation (T cells and monocytes), and
on viral reservoirs (cell associated HIV DNA and RNA) will also be assessed.
;