Effectiveness of Giving an HIV Vaccine (Remune) to HIV-Positive Patients Receiving an Anti-HIV Drug Combination

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00005758
First received: May 23, 2000
Last updated: May 21, 2012
Last verified: May 2012
  Purpose

The purpose of this study is to look at the effects of the HIV vaccine Remune on viral load (level of HIV in the blood) and on the way the immune system responds to HIV. This study will also try to see if the effects of the vaccine are different in patients entering the study with a viral load below 50 copies/ml compared to those who have a viral load from 50 to 500 copies/ml. (This study is currently being redesigned and the purpose may be revised.) Treatment with anti-HIV drugs does not always keep HIV viral load undetectable (so low that it cannot be measured). This study originally added an HIV vaccine called Remune to treat patients. Remune was thought to reduce viral load and improve immune responses. However, new information suggests that Remune may not be as effective as was first believed. The study has been changed to follow people already in the study and to let people enroll only if they participate in the substudy. The substudy will look at the effect of another HIV vaccine, vCP1452, on the immune response and how it works in combination with Remune. Information about the safety of these vaccines in HIV-positive patients will be gathered.


Condition Intervention Phase
HIV Infections
Biological: ALVAC(2)120(B,MN)GNP (vCP1452)
Biological: HIV-1 Immunogen
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Evaluation of the Effect of Immunization With an HIV Immunogen on the Time to Virologic Relapse in Individuals Receiving Potent, Suppressive Antiretroviral Therapies

Resource links provided by NLM:


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

Estimated Enrollment: 472
Study Completion Date: September 2005
Detailed Description:

Studies have shown that inactivated, gp120-depleted whole virus immunogen (Remune) boosts immune responses to HIV. One response, lymphocyte proliferative response (LPR) to p24, is correlated with a low viral load in some patients with long-term non-progression of disease. This study examines whether administering Remune vaccine may generate new immune responses or boost existing responses to keep the level of virus in the blood low for a longer period of time than antiretroviral therapy alone. [AS PER AMENDMENT 7/20/00: In a recent study using Remune, comparison of virologic failure and time to virologic failure between Remune and adjuvant placebo arms revealed no differences between the 2 arms of the study. Results of this study suggest that the hypothesis in A5057 (that recipients of Remune would have only 50 percent of the number of virologic relapses as occur in the control arm) is no longer plausible in its current design. This protocol is being redesigned.] A substudy adds the HIV canarypox vaccine (vCP1452) in patients in the parent study and evaluates whether canarypox vaccine can augment the immune responses of Remune.

Patients will add either Remune (Arm A), or the placebo Incomplete Freund's Adjuvant (Arm B), to their antiretroviral therapy. They will be stratified to 1 of the following 4 groups:

  1. Patients suppressed with 3 or more antiretroviral drugs for 15 months or longer, with an HIV-1 RNA below 50 copies/ml, and who may have substituted 1 antiretroviral medication during that time.
  2. Patients suppressed with 3 or more antiretroviral drugs, who have not taken antiretroviral medications for 15 months or longer, with an HIV-1 RNA below 50 copies/ml, and who may have substituted 1 antiretroviral medication during that time. [AS PER AMENDMENT 7/20/00: This stratum includes patients who have taken their current antiretroviral therapy for less than 15 months prior to screening viral load measurement. If these patients changed from prior antiretroviral regimen(s) during the 15 months prior to screening, they must have changed at least 2 antiretroviral drugs during this time.]
  3. Patients suppressed with 3 or more antiretroviral drugs and whose HIV-1 RNA is 50 copies/ml or higher.
  4. Patients suppressed with 2 antiretroviral drugs. Injections of either Remune or IFA are given at Day 1 and once every 12 weeks for 96 weeks. Patients remain at the clinic for observation for 30 minutes following the first and second injections. If a patient's HIV viral level rises above a certain level, the patient and his/her health care provider may decide to change antiretroviral drugs to try and lower it. Injections will be suspended until the lower level is achieved, then resumed on the regular 12-week schedule. If the decision is not to change therapy, or the viral load does not decrease to under 500 copies/ml within 3 to 4 months, injections may still be received as long as the HIV RNA level is below 5,000 copies/ml. Blood samples are collected prior to every injection to determine CD4/CD8 counts and viral load, to assay for viral presence in peripheral blood mononuclear cells, and to store for future studies. Pregnancy tests for women of reproductive potential, physical exams, and medical histories are done prior to every immunization.

An immunological substudy will randomize 80 of the eligible volunteers from the study cohort to additionally receive ALVAC vCP1452 or placebo (ALVAC) with equal probability. Arm A will receive ALVAC vCP1452; Arm B will be administered placebo.

[AS PER AMENDMENT 7/20/00: The study is closed to accrual except for patients who enroll into A5058s until the protocol can be redesigned. Patients enrolled under Version 1.0 continue to be followed every 12 weeks (plus or minus 14 days) until the end of the study. Patients should continue taking the same potent antiretroviral treatment that they were taking at study entry until reaching the primary endpoint of first virologic relapse.]

  Eligibility

Ages Eligible for Study:   14 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Patients may be eligible for this study if they:

  • Are HIV-positive.
  • Have been on certain anti-HIV drugs for at least 3 months and intend to continue the same anti-HIV drugs unless they develop side effects to the drugs or their viral load rises above a certain level.
  • Have a viral load of less than 500 copies/ml for at least 3 months before entering the study.
  • Have a CD4 count of at least 300 cells/mm3.
  • Are at least 14 years old (consent of parent or guardian required if under 18).
  • Agree to practice barrier methods of birth control (such as condoms) while on the study and for 3 months after the study ends.
  • Patients may be eligible for the substudy if they:
  • Are at least 18 years old.
  • Have a plasma HIV viral load below 50 copies/ml.

Exclusion Criteria

Patients will not be eligible for this study if they:

  • Are pregnant or breast-feeding.
  • Have had an infection requiring antibiotics, an outbreak of herpes simplex virus (HSV) or herpes zoster, or other illness or surgery within 30 days of study entry. (This study has been changed to exclude patients who have had an outbreak of HSV or herpes zoster or have had surgery within 30 days of study entry.)
  • Currently have any long-term infection other than HIV.
  • Have cancer that requires chemotherapy.
  • Have had lymph node irradiation.
  • Have ever received an HIV vaccine.
  • Have taken certain drugs affecting the immune system within 30 days of study entry.
  • Have taken hydroxyurea within 30 days of study entry.
  • Have received any vaccine within 30 days of study entry.
  • Patients will not be eligible for the substudy if they:
  • Have a history of allergies to egg proteins or neomycin, or a history of other serious allergic reactions.
  • Ever worked closely with canaries in a bird shop or breeding farm.
  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: NCT00005758

Locations
United States, California
USC CRS
Los Angeles, California, United States, 900331079
Stanford CRS
Palo Alto, California, United States, 943055107
Ucsf Aids Crs
San Francisco, California, United States, 941102859
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States, 331361013
United States, Hawaii
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States, 96816
United States, Maryland
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States, 02215
Brigham and Women's Hosp. ACTG CRS
Boston, Massachusetts, United States, 02215
Bmc Actg Crs
Boston, Massachusetts, United States
United States, New York
Beth Israel Med. Ctr., ACTU
New York, New York, United States, 10003
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 275997215
United States, Ohio
Case CRS
Cleveland, Ohio, United States, 44106
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, 37203
Sponsors and Collaborators
Investigators
Study Chair: Fred Valentine
Study Chair: Laurence Peiperl
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00005758     History of Changes
Other Study ID Numbers: A5057, 10673, A5058s, ACTG A5057, AACTG A5057
Study First Received: May 23, 2000
Last Updated: May 21, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
T-Lymphocytes, Helper-Inducer
Combined Modality Therapy
HIV Envelope Protein gp120
AIDS Vaccines
RNA, Viral
HIV Core Protein p24
T-Lymphocytes, Cytotoxic
Anti-HIV Agents
Viral Load
HIV Therapeutic Vaccine

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

ClinicalTrials.gov processed this record on October 01, 2014