Clinical trial NCT00482027: Safety and Immunogenicity Study of tgAAC09, a Gag-PR-RT AAV HIV Vaccine
Official title: A Phase 1 Randomized, Placebo-controlled, Double-blind Dose-escalation Trial to Evaluate the Safety and Immunogenicity of tgAAC09, a Gag-PR-RT AAV HIV Vaccine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infection
Keywords: HIV vaccine
Adeno-associated virus vactored vaccine
HIV-1 subtype C
Safety
Immunogenicity
Biodistribution
HIV prevention
Lead sponsor: International AIDS Vaccine Initiative
Sponsor class: NETWORK
Collaborators: name: Targeted Genetics Corporation
name: Children's Hospital of Philadelphia
name: Nationwide Children's Hospital
First posted: 2007-06-04
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine safety and immunogenicity (ability to induce an immune response) of a novel HIV vaccine based on adeno-associated virus (AAV)

Detailed description: The need for a vaccine to prevent AIDS and interrupt transmission of HIV is indisputable. To be effective, an HIV vaccine will have to induce cellular and humoral immune responses that are durable and potent. Intra-muscular delivery of HIV genes enclosed within recombinant adeno-associated virus (rAAV) protein capsid has been shown to be a potent inducer of both antibodies and T-cell responses in animal studies. tgAAC09, consisting of single-stranded DNA from Clade C HIV-1 genes for the gag, protease and part of the reverse transcriptase proteins enclosed within a rAAV serotype 2 protein capsid, was developed as one component of a multi-component HIV vaccine. The purpose of this study is to evaluate the safety and immunogenicity of tgAAC09 in healthy, HIV-seronegative volunteers.

Eligibility criteria: Inclusion Criteria:

* Healthy males and females
* Age at least 18 years on the day of screening and no greater than 50 years on the day of vaccination
* Available for follow-up for the planned duration of the study (screening plus 12 months)
* Able to give written informed consent;
* No reported high-risk behavior for HIV (Appendix C), willing to undergo HIV testing and receive results;
* If sexually active, willing to use or have partner use condoms from screening until at least 4 months after the vaccination. Additional means of contraception are permitted and encouraged.

Exclusion Criteria:

* Clinically relevant abnormality on history or examination including history of immunodeficiency or use of immunosuppressive medication in last 6 months;
* A chronic medical condition or concurrent condition, which, in the opinion of the investigator, would make the volunteer unsuitable for the study.
* Any of the following abnormal laboratory parameters that are mild and judged to be clinically significant by the principal investigator or designee, or moderate, severe, or very severe: hematology (hemoglobin, absolute neutrophil count \[ANC\] absolute lymphocyte count \[ALC\], absolute CD4 count, platelets); urinalysis, clinical chemistry (total bilirubin, creatinine, AST, ALT). Refer to Appendix D for the grading of these laboratory parameters.
* If female, pregnant or planning a pregnancy within 4 months after receiving the vaccine, or lactating;
* Receipt of live attenuated vaccine within 60 days or other vaccine within 14 days of vaccination;
* Receipt of other experimental HIV vaccine at any time;
* Receipt of blood transfusion or blood products within 6 months of vaccination;
* Participation in another clinical trial of an investigational product currently or within 12 weeks of vaccination, or expected during participation in this study;
* History of severe local or systemic reaction to vaccination or history of allergic reactions to vaccines;
* Confirmed infection with HIV-1 or HIV-2;
* Positive for hepatitis B (surface antigen), hepatitis C antibodies, or active syphilis (confirmed by treponemal test such as TPHA in addition to non-treponemal test such as RPR) or active tuberculosis.
* Unlikely to comply with protocol.

Primary outcomes:
measure: Safety of one or two doses of tgAAC09
timeFrame: One year
Secondary outcomes:
measure: Immunogenicity
timeFrame: up to 6 months post 2nd injection
Other outcomes:
measure: Biodistribution
timeFrame: upt to 6 montsh post 1st injection
Locations:
city: Antwerpen
country: Belgium
facility: SGS Biopharma
city: Brussels
country: Belgium
facility: St. Pierre University Hospital
city: Bonn
country: Germany
facility: Univeristy of Bonn
city: Hamburg
country: Germany
facility: University of Hamburg
city: Pune
country: India
facility: National AIDS Research Institute
Study officials:
affiliation: National AIDS Research Institute
name: Sanjay Mehendale, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Pierre University Hospital
name: Nathan Clumeck, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Hamburg-Eppendorf
name: Jan van Lunzen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mehendale S, van Lunzen J, Clumeck N, Rockstroh J, Vets E, Johnson PR, Anklesaria P, Barin B, Boaz M, Kochhar S, Lehrman J, Schmidt C, Peeters M, Schwarze-Zander C, Kabamba K, Glaunsinger T, Sahay S, Thakar M, Paranjape R, Gilmour J, Excler JL, Fast P, Heald AE. A phase 1 study to evaluate the safety and immunogenicity of a recombinant HIV type 1 subtype C adeno-associated virus vaccine. AIDS Res Hum Retroviruses. 2008 Jun;24(6):873-80. doi: 10.1089/aid.2007.0292.
citation: 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.