A Phase 1 Study of CC-11050 in Human Immunodeficiency Virus-1-Infected Adults With Suppressed Plasma Viremia on Antiretroviral Therapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Frequency and severity of AEs and SAEs in subjects receiving study agent vs placebo
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
A
CC-11050 200mg (2 capsules) BID with food
干预措施: Assess Safety (Drug)
A
CC-11050 200mg (2 capsules) BID with food
干预措施: Effect of drug on viral load (Drug)
A
CC-11050 200mg (2 capsules) BID with food
干预措施: Effect of drug on T-cell count (Drug)
A
CC-11050 200mg (2 capsules) BID with food
干预措施: Effect of drug on inflammatory biomarkers (Drug)
B
Placebo (2 capsules) BID with food
干预措施: Assess Safety (Drug)
结局指标
主要结局
Frequency and severity of AEs and SAEs in subjects receiving study agent vs placebo
时间窗: 12/30/2016
次要结局
- CD4+ T cell counts and percentages at weeks 2,4,8 and 12(week 12)
- Plasma HIV-1 RNA levels by both conventional and single-copy assay at Weeks 0,2,4,8, and 12(week 12)
- Markers of systemic inflammation (TNF, IL-6, CRP, IFNy, sCD14, D-dimer) at weeks 2,4,8 and 12(week 12)