Effectiveness of Palifermin in Increasing CD4 Counts in Treatment-Experienced HIV Infected Adults
- Registration Number
- NCT00376935
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 99
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 Palifermin placebo Participants will receive palifermin placebo injection on Days 1, 2, and 3 2 Palifermin Participants will receive palifermin 20 mcg/kg injection on Days 1, 2, and 3 3 Palifermin Participants will receive palifermin 40 mcg/kg injection on Days 1, 2, and 3 4 Palifermin Participants will receive palifermin 60 mcg/kg injection on Days 1, 2, and 3
- Primary Outcome Measures
Name Time Method Change in Absolute CD4+ Lymphocyte Counts From Baseline (Average of Pre-entry and Entry Values) 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.
- Secondary Outcome Measures
Name Time Method Change in CT Thymic Index From Randomization randomization, study week 12 CT thymic index was evaluated at randomization and study week 12, ranging from 0 to 5 whereby 0 means lack of thymic tissue and an organ entirely replaced by fat, 1 means barely recognizable thymic tissue, 2 means minimal soft tissue, 3 means obvious thymic tissue, 4 means moderate thymic tissue, 5 means thymic mass of possible concern for thymoma. Change in CT thymic index from randomization to study week 12 was calculated for participants with both evaluations. The number of participants in each change group was reported by treatment arm.
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 Number of subjects had a grade 3 or 4 toxicity for signs and symptoms. The toxicity grade scale has the following meaning: 1=mild, 2=moderate, 3=severe, 4=life-threatening.
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 subjects had a grade 3 or 4 toxicity for laboratory abnormalities. The toxicity grade scale has the following meaning: 1=mild, 2=moderate, 3=severe, 4=life-threatening.
Number of Death From Randomization to Week 24 From randomization to week 24 Number of subjects died.
Trial Locations
- Locations (22)
Hosp. of the Univ. of Pennsylvania CRS
🇺🇸Philadelphia, Pennsylvania, United States
IHV Baltimore Treatment CRS
🇺🇸Baltimore, Maryland, United States
Bmc Actg Crs
🇺🇸Boston, Massachusetts, United States
MetroHealth CRS
🇺🇸Cleveland, Ohio, United States
University of Washington AIDS CRS
🇺🇸Seattle, Washington, United States
Ucsd, Avrc Crs
🇺🇸San Diego, California, United States
Unc Aids Crs
🇺🇸Chapel Hill, North Carolina, United States
Harbor-UCLA Med. Ctr. CRS
🇺🇸Torrance, California, United States
Case CRS
🇺🇸Cleveland, Ohio, United States
Trillium Health ACTG CRS
🇺🇸Rochester, New York, United States
Univ. of Miami AIDS CRS
🇺🇸Miami, Florida, United States
Vanderbilt Therapeutics CRS
🇺🇸Nashville, Tennessee, United States
USC CRS
🇺🇸Los Angeles, California, United States
UCLA CARE Center CRS
🇺🇸Los Angeles, California, United States
Stanford CRS
🇺🇸Palo Alto, California, United States
Washington U CRS
🇺🇸Saint Louis, Missouri, United States
Univ. of Rochester ACTG CRS
🇺🇸Rochester, New York, United States
Duke Univ. Med. Ctr. Adult CRS
🇺🇸Durham, North Carolina, United States
NY Univ. HIV/AIDS CRS
🇺🇸New York, New York, United States
Columbia P&S CRS
🇺🇸New York, New York, United States
The Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
The Ponce de Leon Ctr. CRS
🇺🇸Atlanta, Georgia, United States