Safety and Immunogenicity Study of tgAAC09, an HIV Vaccine in an Adeno-associated Virus (AAV) Capsid (TGC14F)
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Human Immunodeficiency Virus Infections HIV Infections |
Biological: tgAAC09 Other: Formulation buffer |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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 |
- 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 ] [ Designated as safety issue: Yes ]
- 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 ] [ Designated as safety issue: No ]
- Safety: high versus low or negative titres of neutralizing antibodies to AAV2 at the time of each vaccination [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
- Immunogenicity: proportion of volunteers with HIV-1 specific T- cell responses by γ-IFN CFC or other T-cell assays [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Immunogenicity endpoints after the second study injection, compared with the first study injection [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- Immunogenicity endpoints after the second study injection following a twelve-month interval compared to a six-month interval [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
| Enrollment: | 91 |
| Study Start Date: | October 2005 |
| Study Completion Date: | December 2007 |
| Primary Completion Date: | December 2007 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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
|
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.
Eligibility| Ages Eligible for Study: | 18 Years to 50 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
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| 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 | |
| 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 Uganda Research Unit on Aids |
More Information
Additional Information:
No publications provided
| Responsible Party: | International AIDS Vaccine Initiative |
| ClinicalTrials.gov Identifier: | NCT00888446 History of Changes |
| Other Study ID Numbers: | IAVI A002 |
| Study First Received: | April 23, 2009 |
| Last Updated: | December 13, 2012 |
| Health Authority: | South Africa: Medicines Control Council Uganda: National Council for Science and Technology Zambia: Ministry of Health |
Keywords provided by International AIDS Vaccine Initiative:
|
HIV HIV seronegativity preventative vaccine |
Additional relevant MeSH terms:
|
Acquired Immunodeficiency Syndrome HIV Infections Immunologic Deficiency Syndromes Virus Diseases Lentivirus Infections Retroviridae Infections |
RNA Virus Infections Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Slow Virus Diseases Immune System Diseases |
ClinicalTrials.gov processed this record on June 17, 2013