Effectiveness of Palifermin in Increasing CD4 Counts in Treatment-Experienced HIV Infected Adults

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Palifermin
* Drug: Palifermin placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Participants will receive palifermin placebo injection on Days 1, 2, and 3 | Drug: Palifermin placebo<br>* Keratinocyte growth factor placebo administered via injection<br>* Other names: rHuKGF placebo;|
| Experimental: 2<br>Participants will receive palifermin 20 mcg/kg injection on Days 1, 2, and 3 | Drug: Palifermin<br>* Keratinocyte growth factor administered via injection<br>* Other names: rHuKGF;|
| Experimental: 3<br>Participants will receive palifermin 40 mcg/kg injection on Days 1, 2, and 3 | Drug: Palifermin<br>* Keratinocyte growth factor administered via injection<br>* Other names: rHuKGF;|
| Experimental: 4<br>Participants will receive palifermin 60 mcg/kg injection on Days 1, 2, and 3 | Drug: Palifermin<br>* Keratinocyte growth factor administered via injection<br>* Other names: rHuKGF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Absolute CD4+ Lymphocyte Counts From Baseline (Average of Pre-entry and Entry Values) | 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. | Pre-entry, entry, study week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Qualitative Hepatitis C Virus RNA |  | At study entry | 
| Grade 3 or 4 Toxicity for Signs and Symptoms 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. | 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 | 
| Change in CT Thymic Index From Randomization | 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. | randomization, study week 12 | 
| 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 Lab Toxicities From Randomization to 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. | From randomization to study week 24 | 
| Number of Death From Randomization to Week 24 | Number of subjects died. | From randomization to week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment Experienced