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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00376935
• Other study ID #: A5212
• Secondary ID: 10147ACTG A5212
• Status: Completed
• Phase: Phase 2
• Start date: December 2006
• Est. completion date: September 2008

Study information

• Verified date: January 2019
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 99
• Est. completion date: September 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Palifermin
Keratinocyte growth factor administered via injection
• Palifermin placebo
Keratinocyte growth factor placebo administered via injection

Locations

Country	Name	City	State
United States	The Ponce de Leon Ctr. CRS	Atlanta	Georgia
United States	IHV Baltimore Treatment CRS	Baltimore	Maryland
United States	Bmc Actg Crs	Boston	Massachusetts
United States	Unc Aids Crs	Chapel Hill	North Carolina
United States	Case CRS	Cleveland	Ohio
United States	MetroHealth CRS	Cleveland	Ohio
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	Duke Univ. Med. Ctr. Adult CRS	Durham	North Carolina
United States	UCLA CARE Center CRS	Los Angeles	California
United States	USC CRS	Los Angeles	California
United States	Univ. of Miami AIDS CRS	Miami	Florida
United States	Vanderbilt Therapeutics CRS	Nashville	Tennessee
United States	Columbia P&S CRS	New York	New York
United States	NY Univ. HIV/AIDS CRS	New York	New York
United States	Stanford CRS	Palo Alto	California
United States	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania
United States	Trillium Health ACTG CRS	Rochester	New York
United States	Univ. of Rochester ACTG CRS	Rochester	New York
United States	Washington U CRS	Saint Louis	Missouri
United States	Ucsd, Avrc Crs	San Diego	California
United States	University of Washington AIDS CRS	Seattle	Washington
United States	Harbor-UCLA Med. Ctr. CRS	Torrance	California

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	AIDS Clinical Trials Group

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

Franco JM, Rubio A, Martínez-Moya M, Leal M, Merchante E, Sánchez-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. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Qualitative Hepatitis C Virus RNA		At study entry
Secondary	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
Secondary	Change in Naive CD4+ Cell Counts From Randomization		randomization, day 2, study weeks 1, 2, 4, 8, 12 and 24
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of Death From Randomization to Week 24	Number of subjects died.	From randomization to week 24

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