Safety and Immunogenicity Study of tgAAC09, an HIV Vaccine in an Adeno-associated Virus (AAV) Capsid (TGC14F)

• ClinicalTrials.gov Identifier: NCT00888446
• Recruitment Status: Completed
• First Posted: April 27, 2009
• Last Update Posted: December 17, 2012
• Sponsor: International AIDS Vaccine Initiative
• Collaborator: Targeted Genetics Corporation
• Information provided by (Responsible Party): International AIDS Vaccine Initiative

Study Description

Brief Summary:

This phase 2 study will evaluate the safety, immunogenicity and optimal timing of two injections at three dose levels of the tgAAC09 vaccine in healthy volunteers. Study volunteers will receive two intramuscular injections of tgAAC09 or placebo at Months 0 and 6 (groups A, C, E and G) or at Months 0 and 12 (groups B, D and F) and be followed for a total of 18 months following the first injection with the exception of group G in which volunteers will be followed for 12 months after the first injection (6 months after the second injection). This study will explore whether boosting is possible, and compare a shorter and more practical six-month time interval with a twelve-month time interval.

Condition or disease	Intervention/treatment	Phase
Human Immunodeficiency Virus Infections; HIV Infections	Biological: tgAAC09; Other: Formulation buffer	Phase 2

Detailed Description:

The study design will also assess the effect of the presence of anti-AAV2 capsid neutralizing antibodies at the time of vaccination on the safety and immunogenicity of tgAAC09. Since the prevalence of pre-existing neutralizing antibodies to AAV2 capsid is high (IAVI and Targeted Genetics, data on file), this protocol amendment adds Group G which is composed of volunteers who have documented pre-existing anti-AAV2 capsid neutralizing antibodies titers ≤ 1/8. This will assure that there are sufficient numbers of volunteers with and without antibodies for a useful comparison.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 91 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Phase II, Placebo-controlled, Double-blind, Dose-escalation/Dose-optimization Trial to Evaluate Safety and Immunogenicity of tgAAC09, an HIV Vaccine Containing Clade C Gag-PR-ΔRT DNA in an Adeno-associated Virus (AAV) Capsid
• Study Start Date: October 2005
• Actual Primary Completion Date: December 2007
• Actual Study Completion Date: December 2007

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group A; Number of Vaccine Recipients: 10 Dosage level 3 x 10^10 DRP Month 0 + 6	Biological: tgAAC09
Experimental: Group B; Number of Vaccine Recipients: 10 Dosage level 3 x 10^10 DRP Month 0+12	Biological: tgAAC09
Experimental: Group C; Number of Vaccine Recipients: 10 Dosage level 3 x 10^11 DRP Month 0+6	Biological: tgAAC09
Experimental: Group D; Number of Vaccine Recipients: 10 Dosage level 3 x 10^11 DRP Month 0+12	Biological: tgAAC09
Experimental: Group E; Number of Vaccine Recipients: 10 Dosage level 3 x 10^12 DRP Month 0+6	Biological: tgAAC09
Experimental: Group F; Number of Vaccine Recipients: 10 Dosage level 3 x 10^12 DRP Month 0+12	Biological: tgAAC09
Experimental: Group G; Number of Vaccine Recipients: 10 Preselected for baseline AAV neutralization titers of <1/8 Dosage level 3 x 10^12 DRP Month 0+6	Biological: tgAAC09
Placebo Comparator: Placebo; 3 volunteers will receive placebo matched to each experimental group.	Other: Formulation buffer; Sterile isotonic buffered salt solution

Outcome Measures

Primary Outcome Measures :

1. Safety: proportion of volunteers with severe local and systemic reactions, proportion of volunteers with other SAEs (including laboratory abnormalities) related to study vaccine, number of volunteers with SAEs related to study vaccine [ Time Frame: 18 months ]
2. Proportion of volunteers with HIV-1 specific T- cell responses quantified by γ-IFN ELISPOT and magnitude of the response, and proportion of volunteers with HIV-1 specific binding antibodies and magnitude of the response [ Time Frame: 18 months ]

Secondary Outcome Measures :

1. Safety: high versus low or negative titres of neutralizing antibodies to AAV2 at the time of each vaccination [ Time Frame: 18 months ]
2. Immunogenicity: proportion of volunteers with HIV-1 specific T- cell responses by γ-IFN CFC or other T-cell assays [ Time Frame: 18 months ]
3. Immunogenicity endpoints in volunteers with high versus low or negative titres of neutralizing antibodies to AAV2 at the time of each vaccination [ Time Frame: 18 months ]
4. Immunogenicity endpoints in volunteers with versus without four-fold or greater increase in titres of neutralizing antibodies to AAV2 after vaccination [ Time Frame: 18 months ]
5. Immunogenicity endpoints after the second study injection, compared with the first study injection [ Time Frame: 18 months ]
6. Immunogenicity endpoints after the second study injection following a twelve-month interval compared to a six-month interval [ Time Frame: 18 months ]
7. Vaccine biodistribution: presence and persistence of vaccine in peripheral blood mononuclear cells (PBMC), saliva, nasal swabs, urine and semen or cervical/vaginal secretions [ Time Frame: 18 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Healthy male or female
• Age at least 18 years on the day of screening and no greater than 50 years on the day of the first study injection
• Willing to comply with the requirements of the protocol and available for follow up for the planned duration of the study
• Able and willing to give informed consent.
• Willing to undergo HIV testing, counseling and receive results
• If sexually active female of child-bearing potential (not menopausal or anatomically sterile), willing to use an effective method of contraception (hormonal contraceptives; intrauterine contraceptive device (IUCD); condoms; anatomical sterility in self or partner) from screening until at least four months after last study injection and willing to undergo urine pregnancy tests at screening, prior to each injection and four months after the last injection
• If sexually active male, willing to use a method of contraception (such as condoms) from screening until four months after the last study injection

Exclusion Criteria:

• HIV-1 or HIV-2 infection
• Active tuberculosis
• Clinically relevant abnormality on history or examination including history of immunodeficiency, or cancer, or autoimmune disorder
• Use of systemic corticosteroids, immunosuppressive or anticancer medications in the last six months
• Chronic condition that, in the opinion of the investigator or the designated trial physician, would make the volunteer unsuitable for the study

• Any of the following abnormal laboratory parameters:

  • Hemoglobin <9.0 g/dL (females), <12.0 g/dL (males)
  • Absolute Neutrophil Count (ANC): ≤ 999/mm3
  • Absolute Lymphocyte Count (ALC): ≤ 500/mm3
  • Platelets: decreased ≤ 90,000 or increased ≥ 550,000/mm3
  • Creatinine: > 1.4 x ULN
  • AST: >3.0 x ULN
  • ALT: >3.0 x ULN
  • Urine dipstick: blood = 2+ or more (except in menstruating females); protein = 2+ or more

• Any of the following high-risk behaviors:

  • Had unprotected vaginal or anal sex with a known HIV positive person in the past six months
  • Had unprotected vaginal or anal sex with a casual partner (i.e. no continuing established relationship) in the past six months
  • Engaged in sex work for money or drugs in the past six months
  • Used injection drugs illegally in the past six months
  • Acquired a sexually transmitted infection (STI) in the past six months
• If female, pregnant, lactating or planning a pregnancy within four months after last study injection
• Receipt of live attenuated vaccine within 30 days or other vaccine within 14 days of the first study injection
• Receipt of blood transfusion or blood products six months prior to the first study injection
• Participation in another clinical trial of an investigational product currently or within last 12 weeks of first study injection or expected participation during this study
• Prior receipt of an investigational HIV vaccine
• History of severe local or systemic reaction to vaccination(s) or history of severe allergic reactions
• History of major neurological or psychiatric disorders
• Positive for hepatitis B surface antigen, active untreated syphilis (confirmed by treponemal test such as TPHA in addition to nontreponemal test such as RPR) or other active sexually transmitted diseases

Contacts and Locations

Locations

South Africa

Desmond Tutu HIV Centre Cape Town

Cape Town, South Africa, 7920

Medunsa

South Africa, South Africa, 0204

Perinatal HIV Research Unit, Baragwanath Hospital

Soweto, South Africa, 2013

Uganda

Uganda Virus Research Institute

Entebbe, Uganda

Zambia

Zambia-Emory HIV Research Project (ZEHRP)

Lusaka, Zambia

Sponsors and Collaborators

International AIDS Vaccine Initiative

Targeted Genetics Corporation

Investigators

• Study Chair: Eftyhia Vardas, MD; Perinatal HIV Research Unit (PHRU), Baragwanath
• Principal Investigator: Linda-Gail Bekker, MD; Desmond Tutu HIV Centre Cape Town
• Principal Investigator: Anwar Hoosen; Medical University of Southern Africa (Medunsa)
• Principal Investigator: Elwyn Chomba, MD; Zambia-Emory HIV Research Project (ZEHRP), Lusaka
• Principal Investigator: Pontiano Kaleebu, MD, PhD; MRC/UVRI and LSHTM Uganda Research Unit

More Information

Additional Information:

Related Info 

Publications of Results:

Vardas E, Kaleebu P, Bekker LG, Hoosen A, Chomba E, Johnson PR, Anklesaria P, Birungi J, Barin B, Boaz M, Cox J, Lehrman J, Stevens G, Gilmour J, Tarragona T, Hayes P, Lowenbein S, Kizito E, Fast P, Heald AE, Schmidt C. A phase 2 study to evaluate the safety and immunogenicity of a recombinant HIV type 1 vaccine based on adeno-associated virus. AIDS Res Hum Retroviruses. 2010 Aug;26(8):933-42. doi: 10.1089/aid.2009.0242.

• Responsible Party: International AIDS Vaccine Initiative
• ClinicalTrials.gov Identifier: NCT00888446
• Other Study ID Numbers: IAVI A002
• First Posted: April 27, 2009
• Last Update Posted: December 17, 2012
• Last Verified: December 2012

Keywords provided by International AIDS Vaccine Initiative:

HIV; HIV seronegativity; preventative vaccine

Additional relevant MeSH terms:

Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Disease Attributes; Pathologic Processes; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases