Clinical trial NCT00376935: Effectiveness of Palifermin in Increasing CD4 Counts in Treatment-Experienced HIV Infected Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Treatment Experienced
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
First posted: 2006-09-15
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Change in Absolute CD4+ Lymphocyte Counts From Baseline (Average of Pre-entry and Entry Values)
timeFrame: Pre-entry, entry, study week 12
Secondary outcomes:
measure: Qualitative Hepatitis C Virus RNA
timeFrame: At study entry
measure: Grade 3 or 4 Toxicity for Signs and Symptoms From Randomization to Week 24
timeFrame: From randomization to week 24
measure: Change in Naive CD4+ Cell Counts From Randomization
timeFrame: randomization, day 2, study weeks 1, 2, 4, 8, 12 and 24
measure: Change in CT Thymic Index From Randomization
timeFrame: randomization, study week 12
measure: Change in Absolute CD4+ Lymphocyte Counts From Randomization to Day 2, Weeks 1, 2, 4, 8, 12, 24.
timeFrame: randomization, day 2, study weeks 1, 2, 4, 8, 12 and 24
measure: Grade 3 or 4 Lab Toxicities From Randomization to Week 24
timeFrame: From randomization to study week 24
measure: Number of Death From Randomization to Week 24
timeFrame: From randomization to week 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC CRS
state: California
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS
state: California
city: Palo Alto
country: United States
facility: Stanford CRS
state: California
city: San Diego
country: United States
facility: Ucsd, Avrc Crs
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Med. Ctr. CRS
state: California
city: Miami
country: United States
facility: Univ. of Miami AIDS CRS
state: Florida
city: Atlanta
country: United States
facility: The Ponce de Leon Ctr. CRS
state: Georgia
city: Baltimore
country: United States
facility: IHV Baltimore Treatment CRS
state: Maryland
city: Boston
country: United States
facility: Bmc Actg Crs
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington U CRS
state: Missouri
city: New York
country: United States
facility: NY Univ. HIV/AIDS CRS
state: New York
city: New York
country: United States
facility: Columbia P&S CRS
state: New York
city: Rochester
country: United States
facility: Trillium Health ACTG CRS
state: New York
city: Rochester
country: United States
facility: Univ. of Rochester ACTG CRS
state: New York
city: Chapel Hill
country: United States
facility: Unc Aids Crs
state: North Carolina
city: Durham
country: United States
facility: Duke Univ. Med. Ctr. Adult CRS
state: North Carolina
city: Cleveland
country: United States
facility: Case CRS
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth CRS
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Hosp. of the Univ. of Pennsylvania CRS
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Therapeutics CRS
state: Tennessee
city: Seattle
country: United States
facility: University of Washington AIDS CRS
state: Washington
Study officials:
affiliation: Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine
name: Jeffrey M. Jacobson, MD
role: STUDY_CHAIR
References:
citation: Aiuti F, Mezzaroma I. Failure to reconstitute CD4+ T-cells despite suppression of HIV replication under HAART. AIDS Rev. 2006 Apr-Jun;8(2):88-97.
citation: Franco JM, Rubio A, Martinez-Moya M, Leal M, Merchante E, Sanchez-Quijano A, Lissen E. T-cell repopulation and thymic volume in HIV-1-infected adult patients after highly active antiretroviral therapy. Blood. 2002 May 15;99(10):3702-6. doi: 10.1182/blood.v99.10.3702.
citation: van den Brink MR, Alpdogan O, Boyd RL. Strategies to enhance T-cell reconstitution in immunocompromised patients. Nat Rev Immunol. 2004 Nov;4(11):856-67. doi: 10.1038/nri1484.
citation: Ye P, Kourtis AP, Kirschner DE. Reconstitution of thymic function in HIV-1 patients treated with highly active antiretroviral therapy. Clin Immunol. 2003 Feb;106(2):95-105. doi: 10.1016/s1521-6616(02)00024-4.