A Double Blind Phase II Study of Multiple Doses of Palifermin (rHuKGF) for the Treatment of Inadequate CD4+ Lymphocyte Recovery in Subjects on Potent Antiretroviral Therapy With Plasma HIV-1 RNA Levels of 200 Copies Per Milliliter or Less
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 99
- 试验地点
- 22
- 主要终点
- Change in Absolute CD4+ Lymphocyte Counts From Baseline (Average of Pre-entry and Entry Values)
研究概览
简要总结
Palifermin is a modified version of a naturally occurring human growth factor that is currently approved by the FDA to treat blood cancers. The purpose of this study is to determine whether palifermin can increase CD4 counts in treatment-experienced HIV infected adults.
详细描述
Antiretroviral therapy (ART) has dramatically improved the clinical outcome for HIV infected adults; however, some people on potent ART experience poor recovery of CD4 counts despite maximum suppression of viral load. Such uncontrolled HIV infection is associated with the reduced ability by the human body to create new T cells (or thymopoiesis). HIV infected adults experiencing reduced thymopoiesis are at increased risk of clinical disease progression.
The thymus is the primary site for CD4 cell development; research suggests that keratinocyte growth factor (KGF) may enhance thymus activity in individuals who exhibit reduced thymopoiesis. Palifermin is a modified version of the naturally occurring KGF that is approved to treat people with hematologic malignancies. The purpose of this study is to evaluate the safety and efficacy of palifermin in increasing CD4 counts, through enhanced thymopoiesis, in treatment-experienced HIV infected adults with suppressed viral loads but low CD4 counts.
This study will last 24 weeks. Participants will be randomly assigned to one of four arms:
- Arm A participants will receive placebo
- Arm B participants will receive palifermin 20 mcg/kg
- Arm C participants will receive palifermin 40 mcg/kg
- Arm D participants will receive palifermin 60 mcg/kg
Participants will receive intravenous doses of their assigned intervention on Days 1, 2, and 3. All participants must remain on their current ART regimen for the duration of the study. ART will not be provided by the study. There will be six study visits, and they will occur at Weeks 1, 2, 4, 8, 12, and 24. All visits will include a targeted physical exam and blood and urine collection.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
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
- •HIV infected
- •Receiving potent ART, defined as a combination of three or more antiretroviral drugs for at least 6 months prior to study entry
- •CD4 count of 200 cells/mm3 or less within 30 days prior to study entry
- •Documented CD4 count obtained at study screening
- •Documented current, persistent viral load less than or equal to 200 copies/ml for at least 6 months prior to study entry
- •Willing to use acceptable forms of contraception for the duration of the study
排除标准
- •Active pancreatitis
- •Androgens, Immunomodulators (e.g., growth factors, systemic corticosteroids, HIV vaccines, immune globulin, interleukins, interferons), or investigational ART within 30 days prior to study entry
- •Systemic cancer chemotherapy within 30 days prior to study entry, or history of radiation therapy to the neck and chest regions at any time.
- •Allergy or sensitivity to any component of palifermin
- •Prior treatment with palifermin or other keratinocyte growth factors
- •Current drug or alcohol use that, in the opinion of the investigator, may interfere with study participation
- •Serious illness or recent surgery that requires systemic treatment or hospitalization. Participants who have completed therapy or are clinically stable on therapy for at least 30 days prior to study entry are not excluded.
- •Active cancer
- •HIV-1 RNA levels >200 copies/mL within 6 months prior to study entry
- •Pregnant or breastfeeding
研究组 & 干预措施
1
Participants will receive palifermin placebo injection on Days 1, 2, and 3
干预措施: Palifermin placebo (Drug)
2
Participants will receive palifermin 20 mcg/kg injection on Days 1, 2, and 3
干预措施: Palifermin (Drug)
3
Participants will receive palifermin 40 mcg/kg injection on Days 1, 2, and 3
干预措施: Palifermin (Drug)
4
Participants will receive palifermin 60 mcg/kg injection on Days 1, 2, and 3
干预措施: Palifermin (Drug)
结局指标
主要结局
Change in Absolute CD4+ Lymphocyte Counts From Baseline (Average of Pre-entry and Entry Values)
时间窗: Pre-entry, entry, study week 12
Median and inter-quartile range of the change in absolute CD4 count from baseline to study week 12 were calculated for each treatment arm. Baseline CD4+ count was defined as the average of pre-entry and entry CD4 count. If one evaluation was missing, the other one was used. If a subject missed a week 12 CD4 count evaluation, then the CD4 count evaluation obtained after starting study treatment and closest in time to week 12 (using the earlier evaluation if necessary to break a tie) was used in place of the missing week 12 evaluation.
次要结局
- Change in CT Thymic Index From Randomization(randomization, study week 12)
- Qualitative Hepatitis C Virus RNA(At study entry)
- Change in Absolute CD4+ Lymphocyte Counts From Randomization to Day 2, Weeks 1, 2, 4, 8, 12, 24.(randomization, day 2, study weeks 1, 2, 4, 8, 12 and 24)
- Grade 3 or 4 Toxicity for Signs and Symptoms From Randomization to Week 24(From randomization to week 24)
- Change in Naive CD4+ Cell Counts From Randomization(randomization, day 2, study weeks 1, 2, 4, 8, 12 and 24)
- Grade 3 or 4 Lab Toxicities From Randomization to Week 24(From randomization to study week 24)
- Number of Death From Randomization to Week 24(From randomization to week 24)