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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
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Palifermin
Drug: Palifermin placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 99
Study Start Date: December 2006
Study Completion Date: September 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
Participants will receive palifermin placebo injection on Days 1, 2, and 3
Drug: Palifermin placebo
Keratinocyte growth factor placebo administered via injection
Other Name: rHuKGF placebo
Experimental: 2
Participants will receive palifermin 20 mcg/kg injection on Days 1, 2, and 3
Drug: Palifermin
Keratinocyte growth factor administered via injection
Other Name: rHuKGF
Experimental: 3
Participants will receive palifermin 40 mcg/kg injection on Days 1, 2, and 3
Drug: Palifermin
Keratinocyte growth factor administered via injection
Other Name: rHuKGF
Experimental: 4
Participants will receive palifermin 60 mcg/kg injection on Days 1, 2, and 3
Drug: Palifermin
Keratinocyte growth factor administered via injection
Other Name: rHuKGF

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00376935

Locations
United States, California
UCLA CARE Center CRS
Los Angeles, California, United States, 90035
USC CRS
Los Angeles, California, United States, 90033
Stanford CRS
Palo Alto, California, United States, 94304
Ucsd, Avrc Crs
San Diego, California, United States, 92103
Harbor-UCLA Med. Ctr. CRS
Torrance, California, United States, 90502
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States, 33136-1013
United States, Georgia
The Ponce de Leon Ctr. CRS
Atlanta, Georgia, United States, 30308
United States, Maryland
IHV Baltimore Treatment CRS
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Bmc Actg Crs
Boston, Massachusetts, United States, 02118
United States, Missouri
Washington U CRS
St. Louis, Missouri, United States, 63108-2138
United States, New York
HIV Prevention & Treatment CRS
New York, New York, United States, 10032
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016
Trillium Health ACTG CRS
Rochester, New York, United States, 14607
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 27514
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, United States, 27710
United States, Ohio
Case CRS
Cleveland, Ohio, United States, 44106
MetroHealth CRS
Cleveland, Ohio, United States, 44109
The Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Vanderbilt Therapeutics CRS
Nashville, Tennessee, United States, 37204
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98104
Sponsors and Collaborators
AIDS Clinical Trials Group
Investigators
Study Chair: Jeffrey M. Jacobson, MD Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00376935     History of Changes
Other Study ID Numbers: A5212, 10147, ACTG A5212
Study First Received: September 14, 2006
Results First Received: October 4, 2011
Last Updated: October 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Treatment Experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on November 20, 2014