HIV InfectionsPhase 1NCT00063778
Safety of an HIV Vaccine (AVX101) in HIV Uninfected Volunteers in the United States and South Africa
A Phase 1 study testing AVX101 in people with HIV Infections, run by AlphaVax, Inc. at 7 sites in 2 countries.
Trial summary
The purpose of this study is to see if different doses of an experimental HIV vaccine are safe and to study how the immune system responds to the vaccine. The vaccine will be tested in healthy, HIV uninfected volunteers. Read more about this study
- Who is it for?
- Ages 18 to 60 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
- 48 participants
- Where
- 7 sitesin 2 countries
- Study dates
- Jul 2003to Jul 2005
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- HIV negative
- 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
- Access to participating site and available for follow-up during the 12 month study
Who cannot join
- HIV vaccines or placebos in prior HIV vaccine trial
- Measurable anti-VEE antibody
- High risk for HIV infection according to HVTN Risk Criteria
- 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
Show all 25Show fewer
- Live attenuated vaccines within 30 days prior to first study vaccine administration
- Investigational research agents within 30 days prior to first study vaccine administration
- Subunit or killed vaccines within 14 days prior to first study vaccine administration
- Current tuberculosis prophylaxis or therapy
- Active syphilis
- Serious adverse reaction to vaccines. A person who had an adverse reaction to pertussis vaccine as a child is not excluded.
- Autoimmune disease or immunodeficiency
- Unstable asthma
- Type 1 or Type 2 Diabetes Mellitus
- Thyroid disease requiring treatment
- 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 judgement of the investigator, would interfere with the study
- Pregnant or breast-feeding
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States5 sites
Johns Hopkins University
Baltimore, Maryland, 21205-1901
Vanderbilt University
Nashville, Tennessee, 37232
Columbia University
New York, New York, 10032
University of Rochester Medical Center
Rochester, New York, 14642-0002
New York Blood Ctr- Union Square
The Bronx, New York, 10456
South Africa2 sites
SAAVI Vaccine Research Unit
Durban
Chris Hani Baragwanath Hospital
Soweto
About this study
Official title: A Phase I Safety and Immunogenicity Trial of an Alphavirus Replicon HIV Subtype C Gag Vaccine (AVX101, Alphavax, Inc.) in Healthy HIV-1 Uninfected Adult Volunteers
The purpose of this study is to see if different doses of an experimental HIV vaccine are safe and to study how the immune system responds to the vaccine. The vaccine will be tested in healthy, HIV uninfected volunteers. AVX101 contains only one of the many substances that HIV needs to make more copies of itself; therefore, the vaccine cannot cause HIV or AIDS.
Read the detailed description
This study was designed to evaluate the safety and immunogenicity of an alphavirus replicon HIV subtype C gag vaccine. 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.
This study evaluated the AVX101 vaccine in healthy, HIV uninfected volunteers in both the United States and South Africa. Participants will be randomized to receive either vaccine or placebo at study entry and again at Months 1 and 3. The study was originally designed to enroll four groups of participants in both the US and South Africa, with successive groups receiving increasing doses of the vaccine, but was later amended to enroll only two groups. Twelve US participants (US Group 1) were randomized to receive either vaccine or placebo. After a review of initial safety data from this group, 12 South African participants (SA Group 1) were randomized to receive the same vaccine dose as US Group 1 or placebo, while 12 US participants (US Group 2) were randomized to receive the next higher vaccine dose or placebo. Review of safety data from SA Group 1 and US Group 2 was used to inform the decision to begin enrollment into SA Group 2 .
Participants had nine study visits over 12 months. Study visits included clinical evaluation, urine and blood tests, and HIV tests. After each injection, participants were asked to record their temperature and any symptoms each day for 7 days and report them to the clinic staff.
- Conditions
- HIV Infections
- Being tested
- AVX101, placebo
- Keywords
- HIV Seronegativity, HIV Preventive Vaccine, AIDS Vaccines, Gene Products, gag, HIV-1, Dose-Response Relationship, Immunologic, Injections, Subcutaneous
- 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 10^4 IU dose | Experimental | Vaccine dose of 1 x 10^4 IU per injection Receives: Biological: AVX101 |
| 1 x 10^5 IU dose | Experimental | Vaccine dose of 1 x 10^5 IU per injection Receives: Biological: AVX101 |
| Placebo | Placebo comparator | Not described 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
Lymphoproliferation assay
A lymphocyte proliferation assay in response to purified Gag protein and/or Gag peptides was performed on cryopreserved PBMC collected at baseline, 2 weeks after the second and third vaccinations, and at the final visit.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2003 (estimated)
- Study startJul 2003
- Primary completionJul 2005
- Study completionJul 2005
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
- 48 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 Burke, MD, Study chair, Johns Hopkins UniversitySalim Abdool Karim, MD, PhD, Study chair, University of Natal, Durban, South Africa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00063778
- Sponsor's protocol ID
- HVTN 040
- Status last verified
- Jun 2012
- First submitted
- 7 Jul 2003
- Last updated
- 2 Jul 2012
- Results posted
- No
Publications
Pushko P, Parker M, Ludwig GV, Davis NL, Johnston RE, Smith JF. Replicon-helper systems from attenuated Venezuelan equine encephalitis virus: expression of heterologous genes in vitro and immunization against heterologous pathogens in vivo. Virology. 1997 Dec 22;239(2):389-401. doi: 10.1006/viro.1997.8878.
PubMed 9434729Pushko P, Bray M, Ludwig GV, Parker M, Schmaljohn A, Sanchez A, Jahrling PB, Smith JF. Recombinant RNA replicons derived from attenuated Venezuelan equine encephalitis virus protect guinea pigs and mice from Ebola hemorrhagic fever virus. Vaccine. 2000 Aug 15;19(1):142-53. doi: 10.1016/s0264-410x(00)00113-4.
PubMed 10924796Davis NL, Caley IJ, Brown KW, Betts MR, Irlbeck DM, McGrath KM, Connell MJ, Montefiori DC, Frelinger JA, Swanstrom R, Johnson PR, Johnston RE. Vaccination of macaques against pathogenic simian immunodeficiency virus with Venezuelan equine encephalitis virus replicon particles. J Virol. 2000 Jan;74(1):371-8. doi: 10.1128/jvi.74.1.371-378.2000.
PubMed 10590126Strauss JH, Strauss EG. The alphaviruses: gene expression, replication, and evolution. Microbiol Rev. 1994 Sep;58(3):491-562. doi: 10.1128/mr.58.3.491-562.1994.
PubMed 7968923Wecker 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 Safety and Immunogenicity Trial of an Alphavirus Replicon HIV Subtype C Gag Vaccine (AVX101, Alphavax, Inc.) in Healthy HIV-1 Uninfected Adult Volunteers
- ClinicalTrials.gov ID
- NCT00063778
- Acronym / sponsor ID
- HVTN 040
- Conditions
- HIV Infections
- Keywords
- HIV Seronegativity, HIV Preventive Vaccine, AIDS Vaccines, Gene Products, gag, HIV-1, Dose-Response Relationship, Immunologic, Injections, Subcutaneous
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 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
- Jul 2003
- Primary completion
- Jul 2005 (actual)
- Study completion
- Jul 2005 (actual)
- First posted
- 8 Jul 2003 (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 see if different doses of an experimental HIV vaccine are safe and to study how the immune system responds to the vaccine. The vaccine will be tested in healthy, HIV uninfected volunteers. AVX101 contains only one of the many substances that HIV needs to make more copies of itself; therefore, the vaccine cannot cause HIV or AIDS.
Detailed description
This study was designed to evaluate the safety and immunogenicity of an alphavirus replicon HIV subtype C gag vaccine. 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.
This study evaluated the AVX101 vaccine in healthy, HIV uninfected volunteers in both the United States and South Africa. Participants will be randomized to receive either vaccine or placebo at study entry and again at Months 1 and 3. The study was originally designed to enroll four groups of participants in both the US and South Africa, with successive groups receiving increasing doses of the vaccine, but was later amended to enroll only two groups. Twelve US participants (US Group 1) were randomized to receive either vaccine or placebo. After a review of initial safety data from this group, 12 South African participants (SA Group 1) were randomized to receive the same vaccine dose as US Group 1 or placebo, while 12 US participants (US Group 2) were randomized to receive the next higher vaccine dose or placebo. Review of safety data from SA Group 1 and US Group 2 was used to inform the decision to begin enrollment into SA Group 2 .
Participants had nine study visits over 12 months. Study visits included clinical evaluation, urine and blood tests, and HIV tests. After each injection, participants were asked to record their temperature and any symptoms each day for 7 days and report them to the clinic staff.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 x 10^4 IU dose | Experimental | Biological: AVX101Vaccine dose of 1 x 10^4 IU per injection |
| 1 x 10^5 IU dose | Experimental | Biological: AVX101Vaccine dose of 1 x 10^5 IU per injection |
| Placebo | Placebo comparator | Other: placebo |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- HIV negative
- Willing to receive HIV test results
- Good general health
- Acceptable methods of contraception for females of reproductive potential
- Hepatitis B surface antigen negative
Key exclusion criteria (25 listed)
- HIV vaccines or placebos in prior HIV vaccine trial
- Measurable anti-VEE antibody
- High risk for HIV infection according to HVTN Risk Criteria
- Immunosuppressive medications within 168 days prior to first study vaccine administration
- Blood products within 120 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 10^4 IU dose, 1 x 10^5 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
Lymphoproliferation assay
Time frame: 1 year
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 9434729Pushko P, Parker M, Ludwig GV, Davis NL, Johnston RE, Smith JF. Replicon-helper systems from attenuated Venezuelan equine encephalitis virus: expression of heterologous genes in vitro and immunization against heterologous pathogens in vivo. Virology. 1997 Dec 22;239(2):389-401. doi: 10.1006/viro.1997.8878.
- Background: PubMed 10924796Pushko P, Bray M, Ludwig GV, Parker M, Schmaljohn A, Sanchez A, Jahrling PB, Smith JF. Recombinant RNA replicons derived from attenuated Venezuelan equine encephalitis virus protect guinea pigs and mice from Ebola hemorrhagic fever virus. Vaccine. 2000 Aug 15;19(1):142-53. doi: 10.1016/s0264-410x(00)00113-4.
- Background: PubMed 10590126Davis NL, Caley IJ, Brown KW, Betts MR, Irlbeck DM, McGrath KM, Connell MJ, Montefiori DC, Frelinger JA, Swanstrom R, Johnson PR, Johnston RE. Vaccination of macaques against pathogenic simian immunodeficiency virus with Venezuelan equine encephalitis virus replicon particles. J Virol. 2000 Jan;74(1):371-8. doi: 10.1128/jvi.74.1.371-378.2000.
- Background: PubMed 7968923Strauss JH, Strauss EG. The alphaviruses: gene expression, replication, and evolution. Microbiol Rev. 1994 Sep;58(3):491-562. doi: 10.1128/mr.58.3.491-562.1994.
- 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 Burke, MD study chair
Johns Hopkins University
Salim Abdool Karim, MD, PhD study chair
University of Natal, Durban, South Africa
7 sites in 2 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 7 sites in 2 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 7 inclusion and 25 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 7 sites in United States, 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 NCT00063778, 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.