Safety and Immunogenicity of HIVAX in HIV-1 Infected Subjects

NCT01428596 | Unknown Phase 1 DMC

• 1 other identifier: A010
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to test a therapeutic HIV-1 vaccine (HIVAX™) in HIV-1 infected subjects. The safety and immune responses will be studied in vaccine recipients. The anti-viral effect of HIVAX vaccine will be monitored during a 12-week treatment interruption phase.

Conditions

HIV Infections

Keywords

HIV-1; therapeutic vaccine; immunotherapy; AIDS

Outcome Measures

Primary Outcomes (2)

• • To evaluate the safety of a replication-defective HIV-1 vaccine (HIVAX™) in HIV-1 infected subjects on highly active antiretroviral therapy.

  Frequency and severity of adverse events, laboratory abnormalities, and local and systemic reactogenicity signs and symptoms following vaccinations.

  48 weeks

• • To evaluate the potential immunogenicity of a replication-defective HIV-1 vaccine (HIVAX™) as determined by IFN-γ and IL-2 ELISPOT to pooled gag and env HIV peptides.

  Magnitude of IFN-γ \& IL-2 producing CD4+ and CD8+ T cells to pooled gag and env HIV peptides at 4 weeks post vaccinations.

  48 weeks

Secondary Outcomes (2)

• To explore the potential effectiveness of a replication-defective HIV-1 vaccine as a therapeutic vaccine

  48 weeks

• To monitor the impact of antiretroviral treatment interruption on viral resistance among subjects with virologic rebound (HIV-1 RNA ≥5,000 copies/ml) following resumption of antiretroviral treatment.

  16 weeks

Study Arms (3)

Arm I

EXPERIMENTAL

Lower dose HIVAX vaccine

Biological: HIVAX

Arm II

PLACEBO COMPARATOR

lower dose, placebo control

Biological: saline solution

Arm III

EXPERIMENTAL

Higher dose HIVAX vaccine

Biological: HIVAX

Interventions

HIVAX BIOLOGICAL

Vaccine 1.0 ml SQ lower dose (10\^8 TU) at weeks 0, 8 and 16.

Arm I

saline solution BIOLOGICAL

Saline solution 1.0 ml SQ at weeks 0, 8 and 16.

Arm II

Eligibility Criteria

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

You may qualify if:

• HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by Western blot, at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.
• On highly active antiretroviral therapy defined as the combination of at least three antiretroviral agents for at least 12 months prior to study entry.
• NOTE: A regimen that included only the combination of 3 NRTIs alone will not meet the study definition of a highly active antiretroviral therapy regimen. The combination of low dose ritonavir and another PI will be considered as one antiretroviral agent. Subjects cannot be on an NNRTI containing regimen at study entry.
• Subjects must be on a stable regimen (no change in therapy) for at least 2 months prior to study entry.
• NOTE: A change in formulation or class for reasons other than virologic failure will be allowed but must have documented viral suppression (HIV RNA \<50 copies/ml) on at least two consecutive measurements at least two weeks apart.
• Prior sustained response to antiretroviral therapy defined as an HIV-1 RNA \<50 copies/ml and a CD4 cell count \>500 cells/mm3 for twelve months prior to study entry documented on at least three measurements prior to study entry.
• NOTE: cannot have any confirmed HIV-1 RNA ≥50 copies/ml during the 12-months prior to study entry.
• CD4 cell count \>500 cells/mm3 within 60 days prior to study entry at any laboratory that has a CLIA certification or its equivalent.
• HIV-1 RNA \<50 copies/ml obtained within 30 days prior to study entry by any laboratory that has a CLIA certification or its equivalent.
• Willingness to interrupt all antiretroviral therapy for at least 12 weeks following completion of vaccination phase (Part I).
• Laboratory values obtained within 30 days prior to study entry.
• Absolute neutrophil count (ANC) ≥ 750/mm3.
• Hemoglobin ≥ 8.5 g/dL.
• Platelet count ≥ 75,000/mm3.
• AST (SGOT), ALT (SGPT), and alkaline phosphatase ≤ 2.5 x ULN.

You may not qualify if:

• Active infection with schistosomiasis or Treponema pallidum (syphilis).
• Seropositive for VSV-G antibody, hepatitis B surface antigen (HBsAg) or concurrent chronic active hepatitis C.
• Autoimmune diseases or clinically serious cardiac, pulmonary, gastrointestinal, hepatic, renal or neurologic disease, which in the opinion of the investigator will compromise ability to participate in the study.
• Receipt of immune globulin or blood products within 90 days prior to study entry.
• Receipt of any vaccinations within 30 days prior to study entry.
• Previous receipt of any HIV vaccine. NOTE: Subjects who participated previously in an HIV vaccine trial who have documentation of receipt of only placebo may be eligible after discussion with the protocol chair.
• Pregnancy and breast-feeding.
• Prior systemic cancer chemotherapy,
• Investigational agents and immunomodulators (cyclosporine, hematological growth factors, systemic corticosteroids, interleukins or interferons) within 90 days prior to study entry.
• NOTE: Subjects may be on antiretroviral agents not yet approved by the FDA as part of a clinical trial or expanded access program.
• Anaphylaxis or allergy to vaccine components (See section 5.1.1).
• Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
• Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the investigator, for at least 30 days prior to study entry.
• History of any AIDS-defining illness. NOTE: Subjects whose sole AIDS-defining illness is Kaposi's sarcoma limited to the skin that is not anticipated to require systemic therapy may be eligible after discussion with the protocol chair.
• Nadir CD4 cell count \<250 cell/mm3.

Sponsors & Collaborators

• GeneCure Biotechnologies: lead

Study Sites (1)

University of Miami School of Medicine, AIDS Clinical Research unit

Miami, Florida, 33136, United States

Location

Related Publications (2)

• Pallikkuth S, Bolivar H, Fletcher MA, Babic DZ, De Armas LR, Gupta S, Termini JM, Arheart KL, Stevenson M, Tung FY, Fischl MA, Pahwa S, Stone GW. A therapeutic HIV-1 vaccine reduces markers of systemic immune activation and latent infection in patients under highly active antiretroviral therapy. Vaccine. 2020 Jun 2;38(27):4336-4345. doi: 10.1016/j.vaccine.2020.04.015. Epub 2020 May 6.

  PMID: 32387010 DERIVED

• Tung FY, Tung JK, Pallikkuth S, Pahwa S, Fischl MA. A therapeutic HIV-1 vaccine enhances anti-HIV-1 immune responses in patients under highly active antiretroviral therapy. Vaccine. 2016 Apr 27;34(19):2225-32. doi: 10.1016/j.vaccine.2016.03.021. Epub 2016 Mar 19.

  PMID: 27002500 DERIVED

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Saline Solution

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; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Margaret Fischl, MD

  University of Miami

  STUDY DIRECTOR

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: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2011
• First Posted: September 5, 2011
• Study Start: September 1, 2010
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: June 9, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)