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

NCT00888446 | Completed Phase 2 DMC

• 1 other identifier: IAVI A002
• Study Type: interventional
• Target: 91
• Locations: 2 countries
• Sites: 2

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.

Conditions

Human Immunodeficiency Virus Infections; HIV Infections

Keywords

HIV; HIV seronegativity; preventative vaccine

Outcome Measures

Primary Outcomes (2)

• 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

  18 months

• 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

  18 months

Secondary Outcomes (7)

• Safety: high versus low or negative titres of neutralizing antibodies to AAV2 at the time of each vaccination

  18 months

• Immunogenicity: proportion of volunteers with HIV-1 specific T- cell responses by γ-IFN CFC or other T-cell assays

  18 months

• Immunogenicity endpoints in volunteers with high versus low or negative titres of neutralizing antibodies to AAV2 at the time of each vaccination

  18 months

• Immunogenicity endpoints in volunteers with versus without four-fold or greater increase in titres of neutralizing antibodies to AAV2 after vaccination

  18 months

• Immunogenicity endpoints after the second study injection, compared with the first study injection

  18 months

Study Arms (8)

Group A

EXPERIMENTAL

Number of Vaccine Recipients: 10 Dosage level 3 x 10\^10 DRP Month 0 + 6

Biological: tgAAC09

Group B

EXPERIMENTAL

Number of Vaccine Recipients: 10 Dosage level 3 x 10\^10 DRP Month 0+12

Biological: tgAAC09

Group C

EXPERIMENTAL

Number of Vaccine Recipients: 10 Dosage level 3 x 10\^11 DRP Month 0+6

Biological: tgAAC09

Group D

EXPERIMENTAL

Number of Vaccine Recipients: 10 Dosage level 3 x 10\^11 DRP Month 0+12

Biological: tgAAC09

Group E

EXPERIMENTAL

Number of Vaccine Recipients: 10 Dosage level 3 x 10\^12 DRP Month 0+6

Biological: tgAAC09

Group F

EXPERIMENTAL

Number of Vaccine Recipients: 10 Dosage level 3 x 10\^12 DRP Month 0+12

Biological: tgAAC09

Group G

EXPERIMENTAL

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

PLACEBO COMPARATOR

3 volunteers will receive placebo matched to each experimental group.

Other: Formulation buffer

Interventions

tgAAC09 BIOLOGICAL

Group A; Group B

Formulation buffer OTHER

Sterile isotonic buffered salt solution

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• International AIDS Vaccine Initiative: lead
• Targeted Genetics Corporation: collaborator

Study Sites (5)

Desmond Tutu HIV Centre Cape Town

Cape Town, South Africa, 7920, South Africa

Location

Medunsa

South Africa, South Africa, 0204, South Africa

Location

Perinatal HIV Research Unit, Baragwanath Hospital

Soweto, South Africa, 2013, South Africa

Location

Uganda Virus Research Institute

Entebbe, Entebbe, Uganda

Location

Zambia-Emory HIV Research Project (ZEHRP)

Lusaka, Lusaka Province, Zambia

Location

Related Publications (1)

• 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.

  PMID: 20666584 RESULT

Related Links

• Related Info

MeSH Terms

Conditions

HIV Infections

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

Study Officials

• Eftyhia Vardas, MD

  Perinatal HIV Research Unit (PHRU), Baragwanath

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2009
• First Posted: April 27, 2009
• Study Start: October 1, 2005
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: December 17, 2012

Record last verified: 2012-12

Locations

ZA (1); UG (1)