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

Primary Purpose

Human Immunodeficiency Virus Infections, HIV Infections

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
tgAAC09
tgAAC09
tgAAC09
Formulation buffer
Sponsored by
International AIDS Vaccine Initiative
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Human Immunodeficiency Virus Infections focused on measuring HIV, HIV seronegativity, preventative vaccine

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Desmond Tutu HIV Centre Cape Town
  • Medunsa
  • Perinatal HIV Research Unit, Baragwanath Hospital
  • Uganda Virus Research Institute
  • Zambia-Emory HIV Research Project (ZEHRP)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Group A

Group B

Group C

Group D

Group E

Group F

Group G

Placebo

Arm Description

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

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

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

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

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

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

Number of Vaccine Recipients: 10 Preselected for baseline AAV neutralization titers of <1/8 Dosage level 3 x 10^12 DRP Month 0+6

3 volunteers will receive placebo matched to each experimental group.

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

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

Full Information

First Posted
April 23, 2009
Last Updated
December 13, 2012
Sponsor
International AIDS Vaccine Initiative
Collaborators
Targeted Genetics Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT00888446
Brief Title
Safety and Immunogenicity Study of tgAAC09, an HIV Vaccine in an Adeno-associated Virus (AAV) Capsid
Acronym
TGC14F
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 Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
October 2005 (undefined)
Primary Completion Date
December 2007 (Actual)
Study Completion Date
December 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
International AIDS Vaccine Initiative
Collaborators
Targeted Genetics Corporation

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus Infections, HIV Infections
Keywords
HIV, HIV seronegativity, preventative vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
91 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group A
Arm Type
Experimental
Arm Description
Number of Vaccine Recipients: 10 Dosage level 3 x 10^10 DRP Month 0 + 6
Arm Title
Group B
Arm Type
Experimental
Arm Description
Number of Vaccine Recipients: 10 Dosage level 3 x 10^10 DRP Month 0+12
Arm Title
Group C
Arm Type
Experimental
Arm Description
Number of Vaccine Recipients: 10 Dosage level 3 x 10^11 DRP Month 0+6
Arm Title
Group D
Arm Type
Experimental
Arm Description
Number of Vaccine Recipients: 10 Dosage level 3 x 10^11 DRP Month 0+12
Arm Title
Group E
Arm Type
Experimental
Arm Description
Number of Vaccine Recipients: 10 Dosage level 3 x 10^12 DRP Month 0+6
Arm Title
Group F
Arm Type
Experimental
Arm Description
Number of Vaccine Recipients: 10 Dosage level 3 x 10^12 DRP Month 0+12
Arm Title
Group G
Arm Type
Experimental
Arm Description
Number of Vaccine Recipients: 10 Preselected for baseline AAV neutralization titers of <1/8 Dosage level 3 x 10^12 DRP Month 0+6
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
3 volunteers will receive placebo matched to each experimental group.
Intervention Type
Biological
Intervention Name(s)
tgAAC09
Intervention Type
Biological
Intervention Name(s)
tgAAC09
Intervention Type
Biological
Intervention Name(s)
tgAAC09
Intervention Type
Other
Intervention Name(s)
Formulation buffer
Intervention Description
Sterile isotonic buffered salt solution
Primary Outcome Measure Information:
Title
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
Title
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 Measure Information:
Title
Safety: high versus low or negative titres of neutralizing antibodies to AAV2 at the time of each vaccination
Time Frame
18 months
Title
Immunogenicity: proportion of volunteers with HIV-1 specific T- cell responses by γ-IFN CFC or other T-cell assays
Time Frame
18 months
Title
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
Title
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
Title
Immunogenicity endpoints after the second study injection, compared with the first study injection
Time Frame
18 months
Title
Immunogenicity endpoints after the second study injection following a twelve-month interval compared to a six-month interval
Time Frame
18 months
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eftyhia Vardas, MD
Organizational Affiliation
Perinatal HIV Research Unit (PHRU), Baragwanath
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Linda-Gail Bekker, MD
Organizational Affiliation
Desmond Tutu HIV Centre Cape Town
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anwar Hoosen
Organizational Affiliation
Medical University of Southern Africa (Medunsa)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Elwyn Chomba, MD
Organizational Affiliation
Zambia-Emory HIV Research Project (ZEHRP), Lusaka
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Pontiano Kaleebu, MD, PhD
Organizational Affiliation
MRC/UVRI and LSHTM Uganda Research Unit
Official's Role
Principal Investigator
Facility Information:
Facility Name
Desmond Tutu HIV Centre Cape Town
City
Cape Town
ZIP/Postal Code
7920
Country
South Africa
Facility Name
Medunsa
City
South Africa
ZIP/Postal Code
0204
Country
South Africa
Facility Name
Perinatal HIV Research Unit, Baragwanath Hospital
City
Soweto
ZIP/Postal Code
2013
Country
South Africa
Facility Name
Uganda Virus Research Institute
City
Entebbe
Country
Uganda
Facility Name
Zambia-Emory HIV Research Project (ZEHRP)
City
Lusaka
Country
Zambia

12. IPD Sharing Statement

Citations:
PubMed Identifier
20666584
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.
Results Reference
result
Links:
URL
http://www.iavi.org
Description
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Safety and Immunogenicity Study of tgAAC09, an HIV Vaccine in an Adeno-associated Virus (AAV) Capsid

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