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

Sponsors and Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) Adult AIDS Clinical Trials Group
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00376935

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 II

MedlinePlus related topics: AIDS

Drug Information available for: Palifermin Fibroblast growth factor 7

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver), Placebo Control, Parallel Assignment, Efficacy Study
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

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

Primary Outcome Measures:

Change in absolute CD4 cell count [ Time Frame: Through Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in naive CD4 cell count [ Time Frame: Through Week 12 ] [ Designated as safety issue: No ]
Change in T-cell receptor excision circles (TRECs) [ Time Frame: Through Week 12 ] [ Designated as safety issue: No ]
Occurrence of events for signs and symptoms of Grade 3 or greater [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Percent of CD3 and CD4 T cells enriched in recent thymic emigrants (RTE) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Ratio signal joint TREC (sjTREC)/DBetaJBetaTREC as quantified in peripheral blood mononuclear cell (PBMC) [ Time Frame: At study entry and Week 12 ] [ Designated as safety issue: No ]
sjTREC relative frequency in PBMC [ Time Frame: At study entry and Week 12 ] [ Designated as safety issue: No ]
CT thymic scan results [ Time Frame: At study entry and Week 12 ] [ Designated as safety issue: No ]
Qualitative hepatitis C virus RNA [ Time Frame: At study entry ] [ Designated as safety issue: No ]

Estimated Enrollment:	96
Study Start Date:	December 2006
Estimated Study Completion Date:	March 2009
Primary Completion Date:	April 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Placebo Comparator Participants will receive palifermin placebo injection on Days 1, 2, and 3	Drug: Palifermin placebo Keratinocyte growth factor placebo administered via injection
2: Experimental Participants will receive palifermin 20 mcg/kg injection on Days 1, 2, and 3	Drug: Palifermin Keratinocyte growth factor administered via injection
3: Experimental Participants will receive palifermin 40 mcg/kg injection on Days 1, 2, and 3	Drug: Palifermin Keratinocyte growth factor administered via injection
4: Experimental Participants will receive palifermin 60 mcg/kg injection on Days 1, 2, and 3	Drug: Palifermin Keratinocyte growth factor administered via injection

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 1 participants will receive placebo
Arm 2 participants will receive palifermin 20 mcg/kg
Arm 3 participants will receive palifermin 40 mcg/kg
Arm 4 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 250 cells/mm3 or less
Documented CD4 count obtained at study screening
Documented current, persistent viral load less than 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
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
Pregnant or breastfeeding

Contacts and Locations

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

Show 29 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Adult 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

Haga clic aquí para ver información sobre este ensayo clínico en español This link exits the ClinicalTrials.gov site

Publications:

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. Review.

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.

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. Review.

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.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	ACTG A5212
Study First Received:	September 14, 2006
Last Updated:	August 28, 2008
ClinicalTrials.gov Identifier:	NCT00376935
Health Authority:	United States: Food and Drug Administration

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

Treatment Experienced

Study placed in the following topic categories:

Virus Diseases
Sexually Transmitted Diseases, Viral
HIV Infections
Sexually Transmitted Diseases

Acquired Immunodeficiency Syndrome
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
Lentivirus Infections
Infection

ClinicalTrials.gov processed this record on January 15, 2009