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

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

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.

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.

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