Safety and Effectiveness of Four Anti-HIV Drug Combinations in HIV-Infected Children and Teens

HIV Infections Clinical Trial

Official title:

A Phase II Rolling Arm Master Protocol (PRAM) of Novel Antiretroviral Therapy in Stable Experienced HIV-Infected Children. PRAM-2: A Phase I/II Randomized, Multicenter Protocol Comparing Four Antiretroviral Regimens Containing Combinations of Protease Inhibitors, NRTIs and an NNRTI

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001091
• Other study ID #: ACTG 377
• Secondary ID: 11338PACTG 377
• Status: Completed
• Phase: Phase 1
• Est. completion date: October 2000

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to see if it is safe and effective to give HIV-infected children and teens 1 of 4 anti-HIV drug combinations.

Decreasing HIV levels in infected patients can slow down disease progression. Further study is needed to find out which drug combinations are most effective in doing this.

Description:

For PRAM 2: Evidence suggests that as a consequence of antiviral therapy, decreases in plasma HIV-1 RNA are strongly associated with a delay in clinical progression. Therefore, the drug regimens proposed in this study are designed to result in a much larger sustained drop in plasma HIV-1 RNA and greater clinical benefit. Further intent of this study is to evaluate the virologic and therapeutic potential of novel combinations of antiretrovirals and to better define the pharmacokinetics and drug-drug interactions of therapies included in this regimen.

The Master PRAM schema is designed to allow new therapeutic arms to be studied as "rolling screens" through multiple generations of PRAMs. There is a common, "linking" regimen between any 2 sequential PRAM generations that will permit an indirect comparison of included therapies. (NOTE: Due to significant changes in study design between PRAM 1 and PRAM 2, there is no "linking" arm between them. The linkage will be reinstated from PRAM 2 and subsequent PRAM generations.) The therapeutic potential of the treatment arms is assessed by their ability to decrease HIV copy numbers as defined by plasma HIV-1 RNA copy number. Once accrual to a PRAM is complete, a new treatment comparison will open for accrual.

For PRAM 2: This study will compare the following 4 treatment arms:

Arm A - stavudine (d4T)/nevirapine/ritonavir Arm B - d4T/lamivudine (3TC)/nelfinavir Arm C - d4T/nevirapine/nelfinavir Arm D - d4T/3TC/nevirapine/nelfinavir. Prior to randomization to 1 of the PRAM 2 treatment arms, patients are stratified based on their CD4% (less than 25% and greater than or equal to 25%) and by age (less than 24 months and greater than or equal to 24 months). The first 35 subjects/treatment arm are evaluated with special immunologic studies including lymphoproliferative assays and extended panel immunophenotyping. There is an interim analysis after all patients have completed 12 weeks of treatment. Patients are treated for 48 weeks. [AS PER AMENDMENT 6/11/99: The study has been extended for an additional 48 weeks (96 weeks total) to permit long-term follow-up of clinically stable, HIV-infected children.]

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: October 2000
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Months to 17 Years

Eligibility

Inclusion Criteria

Patients may be eligible for this study if they:

• Are HIV-positive.

• Have received the same continuous anti-HIV treatment for the past 16 weeks (missing no more than 6 weeks of treatment total during those 16 weeks).

• Are between 4 months and 17 years old (consent of parent or guardian required).

Exclusion Criteria

Patients will not be eligible if they:

• Have certain serious conditions such as cancer, an opportunistic (AIDS-related) infection, or other serious infection.

• Have ever taken any of the study drugs or any protease inhibitor.

• Are currently taking any anti-HIV drugs.

• Have taken an investigational drug within 14 days of entry into the study. (Co-enrollment in ACTG 219, ACTG 220 and certain ACTG opportunistic infection studies is allowed.)

• Are taking certain other drugs.

• Are pregnant.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Ritonavir

• Nelfinavir mesylate

• Nevirapine

• Lamivudine

• Stavudine

Locations

Country	Name	City	State
Puerto Rico	Ramon Ruiz Arnau Univ Hosp / Pediatrics	Bayamon
Puerto Rico	San Juan City Hosp	San Juan
United States	Emory Univ Hosp / Pediatrics	Atlanta	Georgia
United States	Med College of Georgia	Augusta	Georgia
United States	Johns Hopkins Hosp - Pediatric	Baltimore	Maryland
United States	Univ of Maryland at Baltimore / Univ Med Ctr	Baltimore	Maryland
United States	Univ of Alabama at Birmingham - Pediatric	Birmingham	Alabama
United States	Bronx Lebanon Hosp Ctr	Bronx	New York
United States	Bronx Municipal Hosp Ctr / Bronx Lebanon Hosp Ctr	Bronx	New York
United States	Bronx Municipal Hosp Ctr/Jacobi Med Ctr	Bronx	New York
United States	King's County Hosp Ctr / Pediatrics	Brooklyn	New York
United States	SUNY - Brooklyn	Brooklyn	New York
United States	Med Univ of South Carolina	Charleston	South Carolina
United States	Chicago Children's Memorial Hosp	Chicago	Illinois
United States	Cook County Hosp	Chicago	Illinois
United States	Univ of Chicago Children's Hosp	Chicago	Illinois
United States	Univ of Illinois College of Medicine / Pediatrics	Chicago	Illinois
United States	North Broward Hosp District	Fort Lauderdale	Florida
United States	Univ of Florida Gainesville	Gainesville	Florida
United States	North Shore Univ Hosp	Great Neck	New York
United States	Connecticut Children's Med Ctr - Pediatric	Hartford	Connecticut
United States	Univ of Mississippi Med Ctr	Jackson	Mississippi
United States	Univ of Florida Health Science Ctr / Pediatrics	Jacksonville	Florida
United States	UCSD Med Ctr / Pediatrics / Clinical Sciences	La Jolla	California
United States	Long Beach Memorial (Pediatric)	Long Beach	California
United States	Children's Hosp of Los Angeles/UCLA Med Ctr	Los Angeles	California
United States	Harbor - UCLA Med Ctr / UCLA School of Medicine	Los Angeles	California
United States	Los Angeles County - USC Med Ctr	Los Angeles	California
United States	UCLA Med Ctr / Pediatric	Los Angeles	California
United States	Vanderbilt Univ Med Ctr	Nashville	Tennessee
United States	UMDNJ - Robert Wood Johnson Med School / Pediatrics	New Brunswick	New Jersey
United States	Yale Univ Med School	New Haven	Connecticut
United States	Schneider Children's Hosp	New Hyde Park	New York
United States	Tulane Univ / Charity Hosp of New Orleans	New Orleans	Louisiana
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Columbia Presbyterian Med Ctr	New York	New York
United States	Cornell Univ Med College	New York	New York
United States	Harlem Hosp Ctr	New York	New York
United States	Incarnation Children's Ctr / Columbia Presbyterian Med Ctr	New York	New York
United States	Metropolitan Hosp Ctr	New York	New York
United States	Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl	Newark	New Jersey
United States	Children's Hosp of the King's Daughters	Norfolk	Virginia
United States	Children's Hosp of Oakland	Oakland	California
United States	Children's Hosp of Philadelphia	Philadelphia	Pennsylvania
United States	Saint Christopher's Hosp for Children	Philadelphia	Pennsylvania
United States	Palm Beach County Health Dept	Riviera Beach	Florida
United States	Univ of Rochester Med Ctr	Rochester	New York
United States	UCSF / Moffitt Hosp - Pediatric	San Francisco	California
United States	Children's Hospital & Medical Center / Seattle ACTU	Seattle	Washington
United States	Baystate Med Ctr of Springfield	Springfield	Massachusetts
United States	State Univ of New York at Stony Brook	Stony Brook	New York
United States	Children's Hosp of Washington DC	Washington	District of Columbia
United States	Howard Univ Hosp	Washington	District of Columbia
United States	Washington Hosp Ctr	Washington	District of Columbia
United States	Univ of Massachusetts Med School	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (9)

Cunningham S, Ank B, Lewis D, Lu W, Wantman M, Dileanis JA, Jackson JB, Palumbo P, Krogstad P, Eshleman SH. Performance of the applied biosystems ViroSeq human immunodeficiency virus type 1 (HIV-1) genotyping system for sequence-based analysis of HIV-1 in pediatric plasma samples. J Clin Microbiol. 2001 Apr;39(4):1254-7. — View Citation

Eshleman SH, Krogstad P, Jackson JB, Lee S, Wang YG, Wei LJ, Cunningham S, Wantman M, Lindquist C, Nachman S, Palumbo P. Analysis of HIV-1 drug resistance in a randomized, controlled trial of a combination of nucleoside analog reverse transcriptase (RT) i

Eshleman SH, Krogstad P, Jackson JB, Wang YG, Lee S, Wei LJ, Cunningham S, Wantman M, Wiznia A, Johnson G, Nachman S, Palumbo P. Analysis of human immunodeficiency virus type 1 drug resistance in children receiving nucleoside analogue reverse-transcriptas — View Citation

Jeremy RJ, Kim S, Nozyce M, Nachman S, McIntosh K, Pelton SI, Yogev R, Wiznia A, Johnson GM, Krogstad P, Stanley K; Pediatric AIDS Clinical Trials Group (PACTG) 338 & 377 Study Teams. Neuropsychological functioning and viral load in stable antiretroviral — View Citation

Krogstad P, Lee S, Johnson G, Stanley K, McNamara J, Moye J, Jackson JB, Aguayo R, Dieudonne A, Khoury M, Mendez H, Nachman S, Wiznia A; Pediatric AIDS Clinical Trials Group 377 Study Team. Nucleoside-analogue reverse-transcriptase inhibitors plus nevirap — View Citation

Rosenblatt HM, Song LY, Nachman SA, Stanley KE, Krogstad PA, Johnson GM, Wiznia AA; Pediatric Aids Clinical Trials Group 377 Study Team. Tetanus immunity after diphtheria, tetanus toxoids, and acellular pertussis vaccination in children with clinically st — View Citation

Saitoh A, Sarles E, Capparelli E, Aweeka F, Kovacs A, Burchett SK, Wiznia A, Nachman S, Fenton T, Spector SA. CYP2B6 genetic variants are associated with nevirapine pharmacokinetics and clinical response in HIV-1-infected children. AIDS. 2007 Oct 18;21(16 — View Citation

Van Dyke RB, Lee S, Johnson GM, Wiznia A, Mohan K, Stanley K, Morse EV, Krogstad PA, Nachman S; Pediatric AIDS Clinical Trials Group Adherence Subcommittee Pediatric AIDS Clinical Trials Group 377 Study Team. Reported adherence as a determinant of respons — View Citation

Wiznia A, Stanley K, Krogstad P, Johnson G, Lee S, McNamara J, Moye J, Jackson JB, Mendez H, Aguayo R, Dieudonne A, Kovacs A, Bamji M, Abrams E, Rana S, Sever J, Nachman S. Combination nucleoside analog reverse transcriptase inhibitor(s) plus nevirapine, — View Citation