HIV InfectionsPhase 1NCT00097838
Safety of and Immune Response to an HIV-1 Subtype C Vaccine (AVX101) in HIV Uninfected Adults
A Phase 1 study testing AVX101 in people with HIV Infections, run by AlphaVax, Inc. at 8 sites in 3 countries.
Trial summary
The purpose of this study is to evaluate the safety of and immune response to an alphavirus replicon, HIV-1 subtype C gag vaccine, AVX101, in HIV uninfected adults in the United States, South Africa, and Botswana. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV Infections
- What is being tested?
- AVX101
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- 8 sitesin 3 countries
- Study dates
- Oct 2004to Sep 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- HIV uninfected
- At low risk for HIV infection
- Willing to receive HIV test results
- Good general health
- Acceptable methods of contraception for females of reproductive potential
- Hepatitis B surface antigen negative
- Anti-hepatitis C virus antibody (anti-HCV) negative or negative HCV PCR if anti-HCV is positive
- Meets educational requirements of the study
Who cannot join
- HIV vaccines or placebos in prior HIV vaccine trial
- Immunosuppressive medications within 168 days prior to first study vaccine administration
- Blood products within 120 days prior to first study vaccine administration
- Immunoglobulin within 60 days prior to first study vaccine administration
- Live attenuated vaccines within 30 days prior to first study vaccine administration
- Investigational research agents within 30 days prior to first study vaccine administration
Show all 24Show fewer
- Subunit or killed vaccines within 14 days prior to first study vaccine administration
- Allergy treatment with antigen injections within 30 days prior to first vaccine administration
- Current tuberculosis prophylaxis or therapy
- Serious adverse reaction to a vaccine. A person who had an adverse reaction to pertussis vaccine as a child is not excluded.
- Autoimmune disease or immunodeficiency
- Active syphilis
- Unstable asthma
- Type 1 or type 2 diabetes mellitus
- Thyroid disease requiring treatment in the past 12 months
- Serious angioedema within the past 3 years
- Uncontrolled hypertension
- Bleeding disorder
- Malignancy unless it has been surgically removed and, in the opinion of the investigator, is not likely to recur during the study period
- Seizure disorder requiring medication within the past 3 years
- Asplenia
- Mental illness that would interfere with compliance with the protocol
- Other conditions that, in the judgment of the investigator, would interfere with the study
- Pregnant or breastfeeding
Trial locations and contacts
8 sites in 3 countries.
8 sites in 3 countries
United States6 sites
Johns Hopkins University
Baltimore, Maryland, 21205-1901
Vanderbilt University
Nashville, Tennessee, 37232
New York Blood Center - Union Square
New York, New York, 10003
Columbia University
New York, New York, 10032
University of Rochester
Rochester, New York, 14642-0001
New York Blood Center - Bronx
The Bronx, New York, 10456
South Africa1 site
Perinatal HIV Research Unit, Chris Hani Baragwanat
Bertsham, 2013
About this study
Official title: A Phase I, Dose Escalation, Safety, and Immunogenicity Trial of an Alphavirus Replicon HIV-1 Subtype C Gag Vaccine (AVX101) in Healthy HIV-1 Uninfected Adult Participants
The purpose of this study is to evaluate the safety of and immune response to an alphavirus replicon, HIV-1 subtype C gag vaccine, AVX101, in HIV uninfected adults in the United States, South Africa, and Botswana.
Read the detailed description
HIV-1 subtype C is the prevailing subtype of HIV found in sub-Saharan Africa and is primarily responsible for the HIV/AIDS epidemic in southern Africa. Thus, development of a preventive subtype C vaccine is critically important in controlling the spread of HIV in this part of the world. This study will determine the safety and immunogenicity of an alphavirus replicon HIV-1 subtype C gag vaccine, AVX101, in HIV uninfected adults. This vaccine utilizes a propagation-defective replicon vector system derived from an attenuated strain of Venezuelan Equine Encephalitis (VEE) virus. The vaccine replicon expresses the gag gene from a South African subtype C isolate of HIV-1. Participants will be recruited in the United States, South Africa, and Botswana.
The study will last for 1 year. Participants will be enrolled sequentially, from lowest to highest dose of vaccine, into one of four groups. Groups will begin enrollment only following safety review of the previous group. Participants will be randomly assigned to receive active vaccine or placebo. During the study, participants will receive either 3 injections of one of four possible doses of the vaccine or 3 injections of placebo. Injections will be given at study entry and at Days 28 and 84. At screening, participants will undergo medical history assessment, a complete physical, HIV testing and counseling, and blood and urine collection; they will also be interviewed and asked to complete a questionnaire. After screening, there will be 8 study visits; the visits will occur at Days 14, 28, 42, 84, 98, 168, 273, and 364. Participants will be interviewed and asked to fill out a questionnaire at each study visit; participants will undergo a physical, additional HIV testing and counseling, and blood and urine collection at selected visits.
- Conditions
- HIV Infections
- Being tested
- AVX101, placebo
- Keywords
- HIV Seronegativity, HIV Preventive Vaccine
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AVX101Biological
Alphavirus replicon particle vaccine expressing HIV Gag antigen
placeboOther
phosphate buffered saline, pH 7.2, HSA, sodium gluconate, and sucrose
| Study group | Role | What they receive |
|---|---|---|
| 1 x 10^5 IU dose | Experimental | Vaccine dose of 1 x 10^5 IU per injection Receives: Biological: AVX101 |
| 1 x 10^6 IU dose | Experimental | Vaccine dose of 1 x 10^6 IU per injection Receives: Biological: AVX101 |
| 1 x 10^7 IU dose | Experimental | Vaccine dose of 1 x 10^7 IU per injection Receives: Biological: AVX101 |
| 1 x 10^8 IU dose | Experimental | Vaccine dose of 1 x 10^8 IU per injection Receives: Biological: AVX101 |
| Placebo | Placebo comparator | phosphate buffered saline, pH 7.2, HSA, sodium gluconate, and sucrose Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Grade IV adverse events
The sample size at each vaccine dose level was selected such that the stopping rule for not escalating the dose (2 or more vaccine-related Grade IV adverse experiences) would be met with high probability if the true toxicity rate was above 15-20%, and such that dose escalation would occur with high probability if the true toxicity rate was less than 5%.
Measured: 1 year
Secondary outcomes (7)
Local and systemic adverse events
Reactogenicity assessments were performed for all participants before and after each injection, beginning 25 to 45 minutes post injection and continuing daily for 7 days. Assessments performed included systemic reactogenicity (body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, nausea, vomiting) and local reactogenicity (injection site pain, tenderness, erythema or induration, and axillary lymph node tenderness or enlargement).
Measured: 7 days after each dose
Binding antibodies by ELISA
Binding antibodies to commercially available Gag protein (P55 Gag; Quality Biologicals) were assessed by ELISA using single serum dilutions (1/50 or 1/100) on samples taken at baseline, two weeks after the second and third vaccinations and at the final visit. Samples that were positive in the initial ELISA were tested by endpoint titration ELISA using six 2- to 7-fold serial dilutions of serum beginning at a 1/50 or 1/100 dilution. Magnitude of responses is reported as the difference in optical density (OD) in antigen-containing and non-antigen containing wells at the 1:50 dilution.
Measured: 1 year
Chromium release CTL assay
A standard 51Cr-release CTL assay was performed on fresh peripheral blood mononuclear cells (PBMC) at baseline and 2 weeks after the second and third vaccinations, using a 50:1 effector to target (E:T) ratio.
Measured: 3 months
IFN-gamma ELISpot assay
Bulk T cell responses were assessed by IFN-γ ELISpot, using cryopreserved PBMC collected at baseline and 2 weeks after the second and third vaccinations, and stimulated overnight with Gag peptide pools at 200,000 cells per well.
Measured: 3 months
Antibodies to VEE virus
Neutralizing antibodies to VEE virus were measured in serum obtained at baseline, 2 weeks after the second and third vaccinations and at the final visit.
Measured: 1 year
Replication-competent viral vector viremia
Any participant who reported a fever greater than 38oC, or other moderate symptoms consistent with a viral illness (e.g. headache or malaise) during the 7 days following vaccination, or neurological symptoms (e.g. nuchal rigidity, ataxia, convulsions, coma, paralysis) within the window of the 2-week post vaccination visit, provided a serum sample to confirm the absence of replication-competent VEE viremia.
Measured: 2 weeks after each vaccine dose
Intracellular cytokine staining (ICS) assay
Flow cytometry was used to examine HIV-specific CD4+ and CD8+ T cell responses using ICS, following stimulation with Gag peptides that span the protein sequence encoded by the vaccine construct. ICS assays were performed at baseline and 2 weeks after the second and third vaccinations.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2004 (estimated)
- Study startOct 2004
- Primary completionSep 2009
- Study completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- AlphaVax, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- HIV Vaccine Trials Network, National Institute of Allergy and Infectious Diseases (NIAID)
- Responsible party
- Sponsor
- Investigators
- Donald S. Burke, MD, Study chair, Center for Immunization Research, Johns Hopkins School of Public HealthSalim Abdool Karim, MD, PhD, Study chair, University of KwaZulu
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00097838
- Sponsor's protocol ID
- HVTN 059
- Status last verified
- Jun 2012
- First submitted
- 30 Nov 2004
- Last updated
- 2 Jul 2012
- Results posted
- No
Publications
Davis NL, West A, Reap E, MacDonald G, Collier M, Dryga S, Maughan M, Connell M, Walker C, McGrath K, Cecil C, Ping LH, Frelinger J, Olmsted R, Keith P, Swanstrom R, Williamson C, Johnson P, Montefiori D, Johnston RE. Alphavirus replicon particles as candidate HIV vaccines. IUBMB Life. 2002 Apr-May;53(4-5):209-11. doi: 10.1080/15216540212657.
PubMed 12120997Williamson AL. The development of HIV-1 subtype C vaccines for Southern Africa. IUBMB Life. 2002 Apr-May;53(4-5):207-8. doi: 10.1080/15216540212648.
PubMed 12120996Williamson C, Morris L, Maughan MF, Ping LH, Dryga SA, Thomas R, Reap EA, Cilliers T, van Harmelen J, Pascual A, Ramjee G, Gray G, Johnston R, Karim SA, Swanstrom R. Characterization and selection of HIV-1 subtype C isolates for use in vaccine development. AIDS Res Hum Retroviruses. 2003 Feb;19(2):133-44. doi: 10.1089/088922203762688649.
PubMed 12639249Schlesinger S. Alphavirus vectors: development and potential therapeutic applications. Expert Opin Biol Ther. 2001 Mar;1(2):177-91. doi: 10.1517/14712598.1.2.177.
PubMed 11727528Wecker M, Gilbert P, Russell N, Hural J, Allen M, Pensiero M, Chulay J, Chiu YL, Abdool Karim SS, Burke DS; HVTN 040/059 Protocol Team; NIAID HIV Vaccine Trials Network. Phase I safety and immunogenicity evaluations of an alphavirus replicon HIV-1 subtype C gag vaccine in healthy HIV-1-uninfected adults. Clin Vaccine Immunol. 2012 Oct;19(10):1651-60. doi: 10.1128/CVI.00258-12. Epub 2012 Aug 22.
PubMed 22914365
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Dose Escalation, Safety, and Immunogenicity Trial of an Alphavirus Replicon HIV-1 Subtype C Gag Vaccine (AVX101) in Healthy HIV-1 Uninfected Adult Participants
- ClinicalTrials.gov ID
- NCT00097838
- Acronym / sponsor ID
- HVTN 059
- Conditions
- HIV Infections
- Keywords
- HIV Seronegativity, HIV Preventive Vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- AlphaVax, Inc.Industry (pharma, biotech, devices)
- Collaborators
- HIV Vaccine Trials Network, National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Oct 2004
- Primary completion
- Sep 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 1 Dec 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety of and immune response to an alphavirus replicon, HIV-1 subtype C gag vaccine, AVX101, in HIV uninfected adults in the United States, South Africa, and Botswana.
Detailed description
HIV-1 subtype C is the prevailing subtype of HIV found in sub-Saharan Africa and is primarily responsible for the HIV/AIDS epidemic in southern Africa. Thus, development of a preventive subtype C vaccine is critically important in controlling the spread of HIV in this part of the world. This study will determine the safety and immunogenicity of an alphavirus replicon HIV-1 subtype C gag vaccine, AVX101, in HIV uninfected adults. This vaccine utilizes a propagation-defective replicon vector system derived from an attenuated strain of Venezuelan Equine Encephalitis (VEE) virus. The vaccine replicon expresses the gag gene from a South African subtype C isolate of HIV-1. Participants will be recruited in the United States, South Africa, and Botswana.
The study will last for 1 year. Participants will be enrolled sequentially, from lowest to highest dose of vaccine, into one of four groups. Groups will begin enrollment only following safety review of the previous group. Participants will be randomly assigned to receive active vaccine or placebo. During the study, participants will receive either 3 injections of one of four possible doses of the vaccine or 3 injections of placebo. Injections will be given at study entry and at Days 28 and 84. At screening, participants will undergo medical history assessment, a complete physical, HIV testing and counseling, and blood and urine collection; they will also be interviewed and asked to complete a questionnaire. After screening, there will be 8 study visits; the visits will occur at Days 14, 28, 42, 84, 98, 168, 273, and 364. Participants will be interviewed and asked to fill out a questionnaire at each study visit; participants will undergo a physical, additional HIV testing and counseling, and blood and urine collection at selected visits.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 1 x 10^5 IU dose | Experimental | Biological: AVX101Vaccine dose of 1 x 10^5 IU per injection |
| 1 x 10^6 IU dose | Experimental | Biological: AVX101Vaccine dose of 1 x 10^6 IU per injection |
| 1 x 10^7 IU dose | Experimental | Biological: AVX101Vaccine dose of 1 x 10^7 IU per injection |
| 1 x 10^8 IU dose | Experimental | Biological: AVX101Vaccine dose of 1 x 10^8 IU per injection |
| Placebo | Placebo comparator | Other: placebophosphate buffered saline, pH 7.2, HSA, sodium gluconate, and sucrose |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- HIV uninfected
- At low risk for HIV infection
- Willing to receive HIV test results
- Good general health
- Acceptable methods of contraception for females of reproductive potential
Key exclusion criteria (24 listed)
- HIV vaccines or placebos in prior HIV vaccine trial
- Immunosuppressive medications within 168 days prior to first study vaccine administration
- Blood products within 120 days prior to first study vaccine administration
- Immunoglobulin within 60 days prior to first study vaccine administration
- Live attenuated vaccines within 30 days prior to first study vaccine administration
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AVX101Alphavirus replicon particle vaccine expressing HIV Gag antigen | Biological | 1 x 10^5 IU dose, 1 x 10^6 IU dose, 1 x 10^7 IU dose, 1 x 10^8 IU dose |
| placebophosphate buffered saline, pH 7.2, HSA, sodium gluconate, and sucrose | Other | Placebo |
Primary outcome
Grade IV adverse events
Time frame: 1 year
The sample size at each vaccine dose level was selected such that the stopping rule for not escalating the dose (2 or more vaccine-related Grade IV adverse experiences) would be met with high probability if the true toxicity rate was above 15-20%, and such that dose escalation would occur with high probability if the true toxicity rate was less than 5%.
7 secondary outcomes
Local and systemic adverse events
Time frame: 7 days after each dose
Binding antibodies by ELISA
Time frame: 1 year
Chromium release CTL assay
Time frame: 3 months
IFN-gamma ELISpot assay
Time frame: 3 months
Antibodies to VEE virus
Time frame: 1 year
Replication-competent viral vector viremia
Time frame: 2 weeks after each vaccine dose
Intracellular cytokine staining (ICS) assay
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2012.
- Background: PubMed 12120997Davis NL, West A, Reap E, MacDonald G, Collier M, Dryga S, Maughan M, Connell M, Walker C, McGrath K, Cecil C, Ping LH, Frelinger J, Olmsted R, Keith P, Swanstrom R, Williamson C, Johnson P, Montefiori D, Johnston RE. Alphavirus replicon particles as candidate HIV vaccines. IUBMB Life. 2002 Apr-May;53(4-5):209-11. doi: 10.1080/15216540212657.
- Background: PubMed 12120996Williamson AL. The development of HIV-1 subtype C vaccines for Southern Africa. IUBMB Life. 2002 Apr-May;53(4-5):207-8. doi: 10.1080/15216540212648.
- Background: PubMed 12639249Williamson C, Morris L, Maughan MF, Ping LH, Dryga SA, Thomas R, Reap EA, Cilliers T, van Harmelen J, Pascual A, Ramjee G, Gray G, Johnston R, Karim SA, Swanstrom R. Characterization and selection of HIV-1 subtype C isolates for use in vaccine development. AIDS Res Hum Retroviruses. 2003 Feb;19(2):133-44. doi: 10.1089/088922203762688649.
- Background: PubMed 11727528Schlesinger S. Alphavirus vectors: development and potential therapeutic applications. Expert Opin Biol Ther. 2001 Mar;1(2):177-91. doi: 10.1517/14712598.1.2.177.
- Derived from this study: PubMed 22914365Wecker M, Gilbert P, Russell N, Hural J, Allen M, Pensiero M, Chulay J, Chiu YL, Abdool Karim SS, Burke DS; HVTN 040/059 Protocol Team; NIAID HIV Vaccine Trials Network. Phase I safety and immunogenicity evaluations of an alphavirus replicon HIV-1 subtype C gag vaccine in healthy HIV-1-uninfected adults. Clin Vaccine Immunol. 2012 Oct;19(10):1651-60. doi: 10.1128/CVI.00258-12. Epub 2012 Aug 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Donald S. Burke, MD study chair
Center for Immunization Research, Johns Hopkins School of Public Health
Salim Abdool Karim, MD, PhD study chair
University of KwaZulu
8 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AVX101 in people with HIV Infections, run by AlphaVax, Inc. at 8 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Botswana, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Grade IV adverse events (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00097838, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2012.