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

This study has been completed.
Sponsor:
Collaborator:
AIDS Clinical Trials Group
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00376935
First received: September 14, 2006
Last updated: October 14, 2014
Last verified: October 2014

September 14, 2006
October 14, 2014
December 2006
July 2008   (final data collection date for primary outcome measure)
Change in Absolute CD4+ Lymphocyte Counts From Baseline (Average of Pre-entry and Entry Values) [ Time Frame: Pre-entry, entry, study week 12 ] [ Designated as safety issue: No ]
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.
Change from baseline to Week 12 in absolute CD4 cell count
Complete list of historical versions of study NCT00376935 on ClinicalTrials.gov Archive Site
  • Change in T-cell Receptor Excision Circles (TRECs)From Randomization [ Time Frame: randomization, study week 12, week 24 ] [ Designated as safety issue: No ]
    Will be posted in the future.
  • Percent of CD3 and CD4 T Cells That Are Enriched in Recent Thymic Emigrants (RTE) [ Time Frame: randomization, study week 12, week 24 ] [ Designated as safety issue: No ]
    Will be posted in the future.
  • Ratio Signal Joint TREC (sjTREC)/DBetaJBetaTREC as Quantified in Peripheral Blood Mononuclear Cell (PBMC) [ Time Frame: randomization, study week 12, week 24 ] [ Designated as safety issue: No ]
    Will be posted in the future.
  • sjTREC Relative Frequency in PBMC [ Time Frame: randomization, study week12, week 24 ] [ Designated as safety issue: No ]
    Will be posted in the future.
  • Qualitative Hepatitis C Virus RNA [ Time Frame: At study entry ] [ Designated as safety issue: No ]
  • Grade 3 or 4 Toxicity for Signs and Symptoms From Randomization to Week 24 [ Time Frame: From randomization to week 24 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: randomization, day 2, study weeks 1, 2, 4, 8, 12 and 24 ] [ Designated as safety issue: No ]
  • Change in CT Thymic Index From Randomization [ Time Frame: randomization, study week 12 ] [ Designated as safety issue: No ]
    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.
  • Change in Absolute CD4+ Lymphocyte Counts From Randomization to Day 2, Weeks 1, 2, 4, 8, 12, 24. [ Time Frame: randomization, day 2, study weeks 1, 2, 4, 8, 12 and 24 ] [ Designated as safety issue: No ]
  • Grade 3 or 4 Lab Toxicities From Randomization to Week 24 [ Time Frame: From randomization to study week 24 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: From randomization to week 24 ] [ Designated as safety issue: Yes ]
    Number of subjects died.
  • Change from baseline to Week 12 in naive CD4 cell count
  • change from baseline to Week 12 in T cell receptor excision circles (TRECs)
  • occurrence of events for signs and symptoms of Grade 3 or greater
  • percent of CD3 and CD4 T cells enriched in recent thymic emigrants (RTE)
  • ratio signal joint TREC (sjTREC)/DBetaJBetaTREC as quantified in peripheral blood mononuclear cell (PBMC) at baseline and Week 12
  • sjTREC relative frequency in PBMC at baseline and Week 12
  • CT thymic scan at study entry and Week 12
  • qualitative hepatitis C virus RNA at study entry
Not Provided
Not Provided
 
Effectiveness of Palifermin in Increasing CD4 Counts in Treatment-Experienced HIV Infected Adults
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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
HIV Infections
  • Drug: Palifermin
    Keratinocyte growth factor administered via injection
    Other Name: rHuKGF
  • Drug: Palifermin placebo
    Keratinocyte growth factor placebo administered via injection
    Other Name: rHuKGF placebo
  • Placebo Comparator: 1
    Participants will receive palifermin placebo injection on Days 1, 2, and 3
    Intervention: Drug: Palifermin placebo
  • Experimental: 2
    Participants will receive palifermin 20 mcg/kg injection on Days 1, 2, and 3
    Intervention: Drug: Palifermin
  • Experimental: 3
    Participants will receive palifermin 40 mcg/kg injection on Days 1, 2, and 3
    Intervention: Drug: Palifermin
  • Experimental: 4
    Participants will receive palifermin 60 mcg/kg injection on Days 1, 2, and 3
    Intervention: Drug: Palifermin

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
99
September 2008
July 2008   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00376935
A5212, 10147, ACTG A5212
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
AIDS Clinical Trials Group
Study Chair: Jeffrey M. Jacobson, MD Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine
National Institute of Allergy and Infectious Diseases (NIAID)
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP