Study of the HIV gp120/NefTat/AS02A Vaccine to Treat Individuals With Chronic HIV-1 Infection on Highly Active Antiretroviral Therapy (HAART)

NCT00117429 | Completed Phase 1

• 2 other identifiers: PARC001GSK: TH-HIV-007
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study will test the safety and immunogenicity of the gp120/NefTat/AS02A vaccine candidate in individuals with chronic HIV-1 infection successfully treated with HAART. The rationale for this study is based on previous scientific experiments, including data indicating that this vaccine can elicit strong HIV-1-specific T cell immune responses in humans and monkeys and lead to a retardation of HIV-1 disease progression in animal models of HIV-1 infection. The HIV vaccine to be administered during this study consists of three recombinant HIV clade B viral antigens: the envelope glycoprotein gp120 and two regulatory proteins, Nef and Tat.The antigens are formulated in a proprietary adjuvant, AS02A, comprised of two immunostimulants in an oil-in-water emulsion (gp120/NefTat/AS02A). The vaccine and the adjuvant are manufactured and provided for the study by GlaxoSmithKline Biologicals, Rixensart, Belgium. The drugs will be given by intramuscular (IM) injection at a standard dose of 20 mg together with 0.5 ml of the AS02A adjuvant. Twenty HIV-1 infected individuals will be randomly enrolled into three different study groups, receiving either the gp120/NefTat/AS02A vaccine (10 individuals), the AS02A adjuvant alone (5 individuals) or a placebo (5 individuals). After obtaining informed consent, subjects will have a history and physical exam performed and have laboratory tests to confirm they meet all inclusion and exclusion entry criteria. Women of childbearing potential will have a pregnancy test prior to each injection of the investigational product. Injections with vaccine, adjuvant alone, or placebo will then be performed at weeks 0, 4, and 12. Study participants will undergo close monitoring after each vaccination. Blood samples will be obtained for immunological assays at study baseline (2 times) and weeks 2, 4, 6, 12, 14, 24, and 48. All patients will maintain their antiretroviral treatment regimen during the entire study period.

Conditions

HIV Infections

Keywords

HIV-1; therapeutic vaccination; cellular immunity; humoral immunity; HAART; chronic HIV-1 infection; Treatment Experienced; HIV Therapeutic Vaccine

Outcome Measures

Primary Outcomes (1)

• Occurrence, intensity and relationship of any local and general signs and symptoms during a 7-day follow-up period (i.e. day of vaccination and 6 subsequent days) after each vaccination

Interventions

HIV gp120/NefTat/AS02A Vaccine BIOLOGICAL

im injection, 0.6-0.7 ml

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• The study will include subjects who meet all of the following criteria:
• Male or female, between 18 to 60 years of age at the time of the first vaccination
• Informed consent signed prior to all study procedures
• No evidence of acute HIV seroconversion in the 12 months prior to the initiation of antiretroviral therapy
• Receiving a potent antiretroviral drug regimen for a minimum of 12 consecutive months prior to screening with no interruption of therapy for \> 2 weeks.
• A potent antiretroviral drug regimen is defined as any of the following: \*two nucleoside reverse transcriptase inhibitors with either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor; \*a boosted protease inhibitor with either one or two nucleoside reverse transcriptase inhibitors or a non-nucleoside reverse transcriptase inhibitor.
• Documented suppressed HIV-1 RNA. Subjects must have plasma HIV-1 RNA values \<50 copies/ml on at least two measurements during the 6 months prior to the study entry.
• CD4+ T cell count \>400 cells/mm3 within 45 days of the first vaccination
• CD4 count \>200 cells/mm3 at all times
• Laboratory values within 45 days prior to the first vaccination that meet the following criteria:
• Hemoglobin \>9.0 g/dL;
• Absolute neutrophil count ≥ 1000/mm3;
• Platelet count ≥ 75,000/mm3;
• Prothrombin time (PT) \< 1.2 x upper limit of normal (ULN) and partial thromboplastin time (PTT) \< 1.5 x ULN;
• Total serum creatinine \< 1.3 x ULN;

You may not qualify if:

• HIV-1 RNA \> 50 copies/mL within 6 months of screening.
• Received antiretroviral therapy within 12 months of known HIV-1 seroconversion.
• History of clinically significant cardiac, pulmonary, gastrointestinal, hepatic, renal, pancreatic, or neurological disease
• Recent (\<24 hours) febrile illness on the day of vaccination (temperature \>101 degrees F, oral)
• History of CD4 count \<200 cells/mm3.
• Female subject who is pregnant or nursing a child
• Received any immune globulin or blood products within 3 months prior to vaccination or plans to receive such products during the study
• Received any live vaccine within 30 days prior to study vaccination or any inactivated vaccine within 14 days prior to study vaccination
• Previously participated in any HIV vaccine clinical trial (unless it is documented that the subject received only placebo)
• History of any AIDS defining illness
• Any change in antiretroviral drug regimen within 12 weeks prior to screening
• Use of any immunomodulatory agents within 30 days prior to study enrollment or planned use during the trial
• Active drug or alcohol use or dependence that, in the opinion of the sponsor, would interfere with adherence to study requirements.
• Any condition or history of illness which, in the opinion of the investigator, might interfere with the evaluation of the study objectives
• Subject has a history of anaphylaxis to any vaccine

Sponsors & Collaborators

• Marcus Altfeld, M.D., Ph.D.: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Massacusetts General Hospital -Infectious Disease Unit

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

HIV Envelope Protein gp120

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

HIV Antigens; Antigens, Viral; Viral Proteins; Proteins; Amino Acids, Peptides, and Proteins; env Gene Products, Human Immunodeficiency Virus; Gene Products, env; Retroviridae Proteins; Human Immunodeficiency Virus Proteins; Viral Envelope Proteins; Viral Structural Proteins; Antigens; Biological Factors

Study Officials

• Marcus Altfeld, MD/PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Mathias Lichterfeld, MD/PhD

  Massachusetts Genral Hosptial

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDIV

Study Record Dates

• First Submitted: June 30, 2005
• First Posted: July 7, 2005
• Study Start: June 1, 2005
• Primary Completion: September 1, 2007
• Study Completion: January 1, 2010
• Last Updated: February 15, 2010

Record last verified: 2010-02

Locations

US (1)