HIV InfectionsPhase 1NCT00083603
Safety of and Immune Response to Two HIV Vaccine Formulations (rMVA-HIV and rFPV-HIV) Alone or in Combination in HIV Uninfected Adults
A Phase 1 study testing rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT), rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT) and Empty TBC-FPV in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 6 sites in 2 countries.
Trial summary
The purpose of this study is to evaluate the safety of and immune response to two HIV vaccine formulations, rMVA-HIV and rFPV-HIV, alone and in combination, in HIV uninfected adults. 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?
- rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT), rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT) and Empty TBC-FPV
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 6 sitesin 2 countries
- Study dates
- Sep 2004to Aug 2007
- 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 within 8 weeks prior to first vaccination
- Blood pressure 140/90 or less upon enrollment
- Good general health
- Willing to receive HIV test results
- Understand the vaccination procedure
- Negative for hepatitis B surface antigen
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- Negative for anti-hepatitis C virus antibodies (anti-HCV) or negative for HCV PCR if anti-HCV is positive
- Willing to use acceptable forms of contraception
- Willing to be followed for the duration of the study
- Have access to a participating HIV vaccine trial site
Who cannot join
- HIV vaccines or placebos in prior HIV vaccine trial
- Previously received Avipox vaccine
- Previously received Vaccinia vaccine
- Immunosuppressive medications within 168 days prior to first vaccination
- Blood products within 120 days prior to first vaccination
- Immunoglobulin within 60 days prior to first vaccination
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- Live attenuated vaccines within 30 days prior to first vaccination
- Investigational research agents within 30 days prior to first vaccination
- Medically indicated subunit or killed vaccines within 14 days prior to first study vaccine administration or allergy treatment with antigen injections within 30 days prior to first vaccination
- Current tuberculosis prophylaxis or therapy
- Hypersensitivity to egg products
- Past or present cardiac disease
- Two or more of the following cardiac risk factors: history of fasting LDL greater than 160 mg/dl; first degree relative who had heart condition, excluding hypertension; cigarette smoking
- ECG with clinically significant findings (e.g., conduction disturbance, repolarization abnormality, significant atrial or ventricular arrhythmia, frequent atrial or ventricular ectopy, ST elevation consistent with ischemia, evidence of past or evolving myocardial infarction)
- 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
- Diabetes mellitus type 1 or 2
- Thyroid disease requiring treatment
- Serious angioedema within the last 3 years
- 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
- Absence of the spleen
- Mental illness that would interfere with the study
- Other conditions that, in the judgment of the investigator, would interfere with the study
- Pregnancy or breastfeeding
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United States4 sites
Alabama Vaccine CRS
Birmingham, Alabama, 35294-2041
Univ. of Rochester HVTN CRS
Rochester, New York, 14642
FHCRC/UW Vaccine CRS
Seattle, Washington, 98104
Saint Louis Univ. School of Medicine, HVTU
St Louis, Missouri, 63110-2500
Brazil2 sites
Projeto Praça Onze/Hesfa Crs
Rio de Janeiro
Sao Paulo HVTU - CRT DST/AIDS CRS
São Paulo
About this study
Official title: A Phase I Trial to Evaluate the Safety and Immunogenicity of rMVA-HIV (rMVA-HIV Env/Gag + rMVA-HIV Tat/Rev/Nef-RT) and rFPV-HIV (rFPV-HIV Env/Gag + rFPV-HIV Tat/Rev/Nef-RT) Vaccines, Alone or in Combination, in Healthy, Vaccinia Naive HIV-1 Negative Participants
The purpose of this study is to evaluate the safety of and immune response to two HIV vaccine formulations, rMVA-HIV and rFPV-HIV, alone and in combination, in HIV uninfected adults.
Read the detailed description
Pox viruses are used for investigational vaccines in humans because they can accommodate large amounts of foreign DNA, can infect mammalian cells, and can access the cytotoxic T-cell responses believed to be important in the control of HIV infection and disease. Two pairs of matching recombinant HIV vaccines have been developed for use in this study. One pair uses a modified vaccinia Ankara (MVA) vector and the other pair uses a fowlpox vector (FPV). Each vaccine pair consists of one vaccine containing env/gag sequences and one vaccine containing modified tat/rev/nef-RT sequences. The HIV sequences are identical and are from a vertically transmitted pediatric primary isolate. The controls in this study are MVA vectors and FPVs without the HIV genes. The study will evaluate the safety and immunogenicity of the vaccine pairs.
There are two parts to this study. Participants in Part A will be randomly assigned to one of five different vaccination groups. Within each group, participants will be randomly assigned to receive either vaccine or control injections. Group 1 participants will receive the FPV vaccine pair or FPV control at each vaccine visit. Groups 2, 3, and 4 will receive one of three different doses of the MVA vaccine pair or MVA control at study entry and Month 1, then a fixed dose of the FPV vaccine pair or FPV control at Months 3, 5, and 7. Group 5 participants will receive the MVA vaccine pair or MVA control at maximum tolerated dose (MTD) at each vaccine visit. Groups 1 and 2 will enroll simultaneously; Groups 3, 4, and 5 will enroll as safety data from the previous groups become available.
In Part B, participants will be randomly assigned to receive study vaccine or control vaccine in one of three vaccination groups. Group 6 participants will receive the FPV vaccine pair or FPV control at each vaccine visit. Group 7 participants will receive the MVA vaccine pair or MVA control at study entry and Month 1, then a fixed dose of the FPV vaccine pair or FPV control at Months 3, 5, and 7. Group 8 participants will receive the MVA vaccine pair at MTD or MVA control at each vaccine visit. Enrollment into Groups 6, 7, and 8 will begin simultaneously after the completion of the safety data evaluation of Groups 1 and 2.
Study vaccinations will be given at study entry and at Months 1, 3, 5 and 7. Tests for cardiac injury will be performed at screening and at each 2-week follow-up visit after vaccination. Participants will have an electrocardiogram (ECG) at screening and 2 weeks after the first and last vaccinations. Study visits will occur at screening, study entry, and at 11 visits over 13 months. Study visits will consist of a physical exam, risk reduction/pregnancy prevention counseling, cardiac symptom assessment, and blood and urine collection. Women will have pregnancy tests at study entry and Months 1, 3, 5, 7, and 13.
- Conditions
- HIV Infections
- Being tested
- rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT), rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT), Empty TBC-FPV, TBC-MVA and TBC-FPV
- Keywords
- HIV Seronegativity, HIV Preventive Vaccine, Vaccinia vector, Pox vector
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT)Biological
rMVA 10^7 pfu /2mL administered in each deltoid
rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT)Biological
Vaccines administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid
Empty TBC-FPVBiological
Empty FPV 10^9 pfu/2mL administered as two separate 1 mL intramuscular injections, one into each deltoid.
rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT)Biological
rMVA 10^8 pfu /2mL administered in each deltoid
rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT)Biological
rMVA 10^9 pfu /2mL administered in each deltoid
TBC-MVA and TBC-FPVBiological
Empty MVA 10^7 pfu/2mL administered into each deltoid
TBC-MVA and TBC-FPVBiological
Empty MVA 10^8 pfu/2mL administered into each deltoid
TBC-MVA and TBC-FPVBiological
Empty MVA 10^9 pfu/2mL administered into each deltoid
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | rFPV-HIV vaccine administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28, 84, 140, and 196 Receives: Biological: rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT) |
| 2 | Placebo comparator | Empty TBC-FPV vector administered as two separate 1-mL intramuscular injections, one into each deltoid at Days 0, 28, 84, 140, and 196 Receives: Biological: Empty TBC-FPV |
| 3 | Experimental | rMVA-HIV env/gag and rMVA-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rMVA-HIV env/gag into the left deltoid, rMVA-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28; rFPV-HIV env/gag and rFPV-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid at Days 84, 140, and 196 Receives: Biological: rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT); Biological: rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT) |
| 4 | Placebo comparator | Empty TBC-MVA vector administered in each deltoid on Days 0, 28; empty TBC-FPV vector administered in each deltoid on Days 84, 140, and 196 Receives: Biological: Empty TBC-FPV; Biological: TBC-MVA and TBC-FPV |
| 5 | Experimental | rMVA-HIV env/gag and rMVA-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rMVA-HIV env/gag into the left deltoid, rMVA-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28; rFPV-HIV env/gag and rFPV-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid at Days 84, 140, and 196 Receives: Biological: rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT); Biological: rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT) |
| 6 | Placebo comparator | Empty TBC-MVA vector administered in each deltoid Days 0, 28; empty TBC-FPV vector administered in each deltoid Days 84, 140, and 196 Receives: Biological: Empty TBC-FPV; Biological: TBC-MVA and TBC-FPV |
| 7 | Experimental | rMVA-HIV env/gag and rMVA-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rMVA-HIV env/gag into the left deltoid, rMVA-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28; rFPV-HIV env/gag and rFPV-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid at Days 84, 140, and 196 Receives: Biological: rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT); Biological: rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT) |
| 8 | Placebo comparator | Empty TBC-MVA vector administered in each deltoid Days 0, 28; empty TBC-FPV vector administered in each deltoid Days 84, 140, and 196 Receives: Biological: Empty TBC-FPV; Biological: TBC-MVA and TBC-FPV |
| 9 | Experimental | rMVA-HIV env/gag and rMVA-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rMVA-HIV env/gag into the left deltoid, rMVA-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28, 84, 140, 196 Receives: Biological: rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT) |
| 10 | Placebo comparator | Empty TBC-MVA vector administered in each deltoid Days 0, 28, 84, 140, 196 Receives: Biological: TBC-MVA and TBC-FPV |
| 11 | Experimental | rFPV-HIV vaccine administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28, 84, 140, and 196 Receives: Biological: rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT) |
| 12 | Placebo comparator | Empty TBC-FPV vector administered as two separate 1-mL intramuscular injections, one into each deltoid at Days 0, 28, 84, 140, and 196 Receives: Biological: Empty TBC-FPV |
| 13 | Experimental | rMVA-HIV env/gag and rMVA-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rMVA-HIV env/gag into the left deltoid, rMVA-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28; rFPV-HIV env/gag and rFPV-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid at Days 84, 140, and 196 Receives: Biological: rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT); Biological: rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT) |
| 14 | Placebo comparator | Empty TBC-MVA vector administered in each deltoid Days 0, 28; empty TBC-FPV vector administered in each deltoid Days 84, 140, and 196 Receives: Biological: Empty TBC-FPV; Biological: TBC-MVA and TBC-FPV |
| 15 | Experimental | rMVA-HIV env/gag and rMVA-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rMVA-HIV env/gag into the left deltoid, rMVA-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28, 84, 140, 196 Receives: Biological: rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT) |
| 16 | Placebo comparator | Empty TBC-MVA vector administered in each deltoid Days 0, 28, 84, 140, 196 Receives: Biological: TBC-MVA and TBC-FPV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability, as judged by local and systemic reactogenicity signs and symptoms, laboratory measures, and adverse events
Measured: After each injection and 12 months after the first injection
Immunogenicity, as judged by qualitative HIV-1-specific T-cell responses
Measured: At Days 98 and 210
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2004 (estimated)
- Study startSep 2004
- Study completionAug 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Michael Keefer, MD, Study chair, University of RochesterSharon Frey, MD, Study chair, St. Louis University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00083603
- Sponsor's protocol ID
- HVTN 055
- Other IDs
- 10056
- Status last verified
- Oct 2021
- First submitted
- 26 May 2004
- Last updated
- 14 Oct 2021
- Results posted
- No
Publications
Amara RR, Villinger F, Altman JD, Lydy SL, O'Neil SP, Staprans SI, Montefiori DC, Xu Y, Herndon JG, Wyatt LS, Candido MA, Kozyr NL, Earl PL, Smith JM, Ma HL, Grimm BD, Hulsey ML, Miller J, McClure HM, McNicholl JM, Moss B, Robinson HL. Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine. Science. 2001 Apr 6;292(5514):69-74. doi: 10.1126/science.1058915.
PubMed 11393868Blanchard TJ, Alcami A, Andrea P, Smith GL. Modified vaccinia virus Ankara undergoes limited replication in human cells and lacks several immunomodulatory proteins: implications for use as a human vaccine. J Gen Virol. 1998 May;79 ( Pt 5):1159-67. doi: 10.1099/0022-1317-79-5-1159.
PubMed 9603331Hanke T, McMichael AJ, Mwau M, Wee EG, Ceberej I, Patel S, Sutton J, Tomlinson M, Samuel RV. Development of a DNA-MVA/HIVA vaccine for Kenya. Vaccine. 2002 May 6;20(15):1995-8. doi: 10.1016/s0264-410x(02)00085-3.
PubMed 11983261Kent SJ, Zhao A, Best SJ, Chandler JD, Boyle DB, Ramshaw IA. Enhanced T-cell immunogenicity and protective efficacy of a human immunodeficiency virus type 1 vaccine regimen consisting of consecutive priming with DNA and boosting with recombinant fowlpox virus. J Virol. 1998 Dec;72(12):10180-8. doi: 10.1128/JVI.72.12.10180-10188.1998.
PubMed 9811759Stratov I, DeRose R, Purcell DF, Kent SJ. Vaccines and vaccine strategies against HIV. Curr Drug Targets. 2004 Jan;5(1):71-88. doi: 10.2174/1389450043490686.
PubMed 14738219Ramjee G, Kapiga S, Weiss S, Peterson L, Leburg C, Kelly C, Masse B; HPTN 055 Study Team. The value of site preparedness studies for future implementation of phase 2/IIb/III HIV prevention trials: experience from the HPTN 055 study. J Acquir Immune Defic Syndr. 2008 Jan 1;47(1):93-100. doi: 10.1097/QAI.0b013e31815c71f7.
PubMed 17984760Elizaga ML, Vasan S, Marovich MA, Sato AH, Lawrence DN, Chaitman BR, Frey SE, Keefer MC; MVA Cardiac Safety Working Group. Prospective surveillance for cardiac adverse events in healthy adults receiving modified vaccinia Ankara vaccines: a systematic review. PLoS One. 2013;8(1):e54407. doi: 10.1371/journal.pone.0054407. Epub 2013 Jan 17.
PubMed 23349878Walsh SR, Seaman MS, Grandpre LE, Charbonneau C, Yanosick KE, Metch B, Keefer MC, Dolin R, Baden LR. Impact of anti-orthopoxvirus neutralizing antibodies induced by a heterologous prime-boost HIV-1 vaccine on insert-specific immune responses. Vaccine. 2012 Dec 17;31(1):114-9. doi: 10.1016/j.vaccine.2012.10.093. Epub 2012 Nov 7.
PubMed 23142302Keefer MC, Frey SE, Elizaga M, Metch B, De Rosa SC, Barroso PF, Tomaras G, Cardinali M, Goepfert P, Kalichman A, Philippon V, McElrath MJ, Jin X, Ferrari G, Defawe OD, Mazzara GP, Montefiori D, Pensiero M, Panicali DL, Corey L; NIAID HIV Vaccine Trials Network. A phase I trial of preventive HIV vaccination with heterologous poxviral-vectors containing matching HIV-1 inserts in healthy HIV-uninfected subjects. Vaccine. 2011 Feb 24;29(10):1948-58. doi: 10.1016/j.vaccine.2010.12.104. Epub 2011 Jan 7.
PubMed 21216311
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial to Evaluate the Safety and Immunogenicity of rMVA-HIV (rMVA-HIV Env/Gag + rMVA-HIV Tat/Rev/Nef-RT) and rFPV-HIV (rFPV-HIV Env/Gag + rFPV-HIV Tat/Rev/Nef-RT) Vaccines, Alone or in Combination, in Healthy, Vaccinia Naive HIV-1 Negative Participants
- ClinicalTrials.gov ID
- NCT00083603
- Acronym / sponsor ID
- HVTN 055
- Conditions
- HIV Infections
- Keywords
- HIV Seronegativity, HIV Preventive Vaccine, Vaccinia vector, Pox vector
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Sep 2004
- Study completion
- Aug 2007 (actual)
- First posted
- 27 May 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 two HIV vaccine formulations, rMVA-HIV and rFPV-HIV, alone and in combination, in HIV uninfected adults.
Detailed description
Pox viruses are used for investigational vaccines in humans because they can accommodate large amounts of foreign DNA, can infect mammalian cells, and can access the cytotoxic T-cell responses believed to be important in the control of HIV infection and disease. Two pairs of matching recombinant HIV vaccines have been developed for use in this study. One pair uses a modified vaccinia Ankara (MVA) vector and the other pair uses a fowlpox vector (FPV). Each vaccine pair consists of one vaccine containing env/gag sequences and one vaccine containing modified tat/rev/nef-RT sequences. The HIV sequences are identical and are from a vertically transmitted pediatric primary isolate. The controls in this study are MVA vectors and FPVs without the HIV genes. The study will evaluate the safety and immunogenicity of the vaccine pairs.
There are two parts to this study. Participants in Part A will be randomly assigned to one of five different vaccination groups. Within each group, participants will be randomly assigned to receive either vaccine or control injections. Group 1 participants will receive the FPV vaccine pair or FPV control at each vaccine visit. Groups 2, 3, and 4 will receive one of three different doses of the MVA vaccine pair or MVA control at study entry and Month 1, then a fixed dose of the FPV vaccine pair or FPV control at Months 3, 5, and 7. Group 5 participants will receive the MVA vaccine pair or MVA control at maximum tolerated dose (MTD) at each vaccine visit. Groups 1 and 2 will enroll simultaneously; Groups 3, 4, and 5 will enroll as safety data from the previous groups become available.
In Part B, participants will be randomly assigned to receive study vaccine or control vaccine in one of three vaccination groups. Group 6 participants will receive the FPV vaccine pair or FPV control at each vaccine visit. Group 7 participants will receive the MVA vaccine pair or MVA control at study entry and Month 1, then a fixed dose of the FPV vaccine pair or FPV control at Months 3, 5, and 7. Group 8 participants will receive the MVA vaccine pair at MTD or MVA control at each vaccine visit. Enrollment into Groups 6, 7, and 8 will begin simultaneously after the completion of the safety data evaluation of Groups 1 and 2.
Study vaccinations will be given at study entry and at Months 1, 3, 5 and 7. Tests for cardiac injury will be performed at screening and at each 2-week follow-up visit after vaccination. Participants will have an electrocardiogram (ECG) at screening and 2 weeks after the first and last vaccinations. Study visits will occur at screening, study entry, and at 11 visits over 13 months. Study visits will consist of a physical exam, risk reduction/pregnancy prevention counseling, cardiac symptom assessment, and blood and urine collection. Women will have pregnancy tests at study entry and Months 1, 3, 5, 7, and 13.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 16
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT)rFPV-HIV vaccine administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28, 84, 140, and 196 |
| 2 | Placebo comparator | Biological: Empty TBC-FPVEmpty TBC-FPV vector administered as two separate 1-mL intramuscular injections, one into each deltoid at Days 0, 28, 84, 140, and 196 |
| 3 | Experimental | Biological: rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT), Biological: rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT)rMVA-HIV env/gag and rMVA-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rMVA-HIV env/gag into the left deltoid, rMVA-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28; rFPV-HIV env/gag and rFPV-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid at Days 84, 140, and 196 |
| 4 | Placebo comparator | Biological: Empty TBC-FPV, Biological: TBC-MVA and TBC-FPVEmpty TBC-MVA vector administered in each deltoid on Days 0, 28; empty TBC-FPV vector administered in each deltoid on Days 84, 140, and 196 |
| 5 | Experimental | Biological: rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT), Biological: rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT)rMVA-HIV env/gag and rMVA-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rMVA-HIV env/gag into the left deltoid, rMVA-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28; rFPV-HIV env/gag and rFPV-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid at Days 84, 140, and 196 |
| 6 | Placebo comparator | Biological: Empty TBC-FPV, Biological: TBC-MVA and TBC-FPVEmpty TBC-MVA vector administered in each deltoid Days 0, 28; empty TBC-FPV vector administered in each deltoid Days 84, 140, and 196 |
| 7 | Experimental | Biological: rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT), Biological: rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT)rMVA-HIV env/gag and rMVA-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rMVA-HIV env/gag into the left deltoid, rMVA-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28; rFPV-HIV env/gag and rFPV-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid at Days 84, 140, and 196 |
| 8 | Placebo comparator | Biological: Empty TBC-FPV, Biological: TBC-MVA and TBC-FPVEmpty TBC-MVA vector administered in each deltoid Days 0, 28; empty TBC-FPV vector administered in each deltoid Days 84, 140, and 196 |
| 9 | Experimental | Biological: rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT)rMVA-HIV env/gag and rMVA-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rMVA-HIV env/gag into the left deltoid, rMVA-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28, 84, 140, 196 |
| 10 | Placebo comparator | Biological: TBC-MVA and TBC-FPVEmpty TBC-MVA vector administered in each deltoid Days 0, 28, 84, 140, 196 |
| 11 | Experimental | Biological: rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT)rFPV-HIV vaccine administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28, 84, 140, and 196 |
| 12 | Placebo comparator | Biological: Empty TBC-FPVEmpty TBC-FPV vector administered as two separate 1-mL intramuscular injections, one into each deltoid at Days 0, 28, 84, 140, and 196 |
| 13 | Experimental | Biological: rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT), Biological: rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT)rMVA-HIV env/gag and rMVA-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rMVA-HIV env/gag into the left deltoid, rMVA-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28; rFPV-HIV env/gag and rFPV-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid at Days 84, 140, and 196 |
| 14 | Placebo comparator | Biological: Empty TBC-FPV, Biological: TBC-MVA and TBC-FPVEmpty TBC-MVA vector administered in each deltoid Days 0, 28; empty TBC-FPV vector administered in each deltoid Days 84, 140, and 196 |
| 15 | Experimental | Biological: rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT)rMVA-HIV env/gag and rMVA-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rMVA-HIV env/gag into the left deltoid, rMVA-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28, 84, 140, 196 |
| 16 | Placebo comparator | Biological: TBC-MVA and TBC-FPVEmpty TBC-MVA vector administered in each deltoid Days 0, 28, 84, 140, 196 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- HIV uninfected within 8 weeks prior to first vaccination
- Blood pressure 140/90 or less upon enrollment
- Good general health
- Willing to receive HIV test results
- Understand the vaccination procedure
Key exclusion criteria (27 listed)
- HIV vaccines or placebos in prior HIV vaccine trial
- Previously received Avipox vaccine
- Previously received Vaccinia vaccine
- Immunosuppressive medications within 168 days prior to first vaccination
- Blood products within 120 days prior to first vaccination
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 |
|---|---|---|
| rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT)rMVA 10^7 pfu /2mL administered in each deltoid | Biological | 3 |
| rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT)Vaccines administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid | Biological | 1, 11, 13, 3, 5, 7 |
| Empty TBC-FPVEmpty FPV 10^9 pfu/2mL administered as two separate 1 mL intramuscular injections, one into each deltoid. | Biological | 12, 14, 2, 4, 6, 8 |
| rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT)rMVA 10^8 pfu /2mL administered in each deltoid | Biological | 5 |
| rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT)rMVA 10^9 pfu /2mL administered in each deltoid | Biological | 13, 15, 7, 9 |
| TBC-MVA and TBC-FPVEmpty MVA 10^7 pfu/2mL administered into each deltoid | Biological | 4 |
| TBC-MVA and TBC-FPVEmpty MVA 10^8 pfu/2mL administered into each deltoid | Biological | 6 |
| TBC-MVA and TBC-FPVEmpty MVA 10^9 pfu/2mL administered into each deltoid | Biological | 10, 14, 16, 8 |
Primary outcome
Safety and tolerability, as judged by local and systemic reactogenicity signs and symptoms, laboratory measures, and adverse events
Time frame: After each injection and 12 months after the first injection
Immunogenicity, as judged by qualitative HIV-1-specific T-cell responses
Time frame: At Days 98 and 210
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 14 Oct 2021.
- Background: PubMed 11393868Amara RR, Villinger F, Altman JD, Lydy SL, O'Neil SP, Staprans SI, Montefiori DC, Xu Y, Herndon JG, Wyatt LS, Candido MA, Kozyr NL, Earl PL, Smith JM, Ma HL, Grimm BD, Hulsey ML, Miller J, McClure HM, McNicholl JM, Moss B, Robinson HL. Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine. Science. 2001 Apr 6;292(5514):69-74. doi: 10.1126/science.1058915.
- Background: PubMed 9603331Blanchard TJ, Alcami A, Andrea P, Smith GL. Modified vaccinia virus Ankara undergoes limited replication in human cells and lacks several immunomodulatory proteins: implications for use as a human vaccine. J Gen Virol. 1998 May;79 ( Pt 5):1159-67. doi: 10.1099/0022-1317-79-5-1159.
- Background: PubMed 11983261Hanke T, McMichael AJ, Mwau M, Wee EG, Ceberej I, Patel S, Sutton J, Tomlinson M, Samuel RV. Development of a DNA-MVA/HIVA vaccine for Kenya. Vaccine. 2002 May 6;20(15):1995-8. doi: 10.1016/s0264-410x(02)00085-3.
- Background: PubMed 9811759Kent SJ, Zhao A, Best SJ, Chandler JD, Boyle DB, Ramshaw IA. Enhanced T-cell immunogenicity and protective efficacy of a human immunodeficiency virus type 1 vaccine regimen consisting of consecutive priming with DNA and boosting with recombinant fowlpox virus. J Virol. 1998 Dec;72(12):10180-8. doi: 10.1128/JVI.72.12.10180-10188.1998.
- Background: PubMed 14738219Stratov I, DeRose R, Purcell DF, Kent SJ. Vaccines and vaccine strategies against HIV. Curr Drug Targets. 2004 Jan;5(1):71-88. doi: 10.2174/1389450043490686.
- Results publication: PubMed 17984760Ramjee G, Kapiga S, Weiss S, Peterson L, Leburg C, Kelly C, Masse B; HPTN 055 Study Team. The value of site preparedness studies for future implementation of phase 2/IIb/III HIV prevention trials: experience from the HPTN 055 study. J Acquir Immune Defic Syndr. 2008 Jan 1;47(1):93-100. doi: 10.1097/QAI.0b013e31815c71f7.
- Derived from this study: PubMed 23349878Elizaga ML, Vasan S, Marovich MA, Sato AH, Lawrence DN, Chaitman BR, Frey SE, Keefer MC; MVA Cardiac Safety Working Group. Prospective surveillance for cardiac adverse events in healthy adults receiving modified vaccinia Ankara vaccines: a systematic review. PLoS One. 2013;8(1):e54407. doi: 10.1371/journal.pone.0054407. Epub 2013 Jan 17.
- Derived from this study: PubMed 23142302Walsh SR, Seaman MS, Grandpre LE, Charbonneau C, Yanosick KE, Metch B, Keefer MC, Dolin R, Baden LR. Impact of anti-orthopoxvirus neutralizing antibodies induced by a heterologous prime-boost HIV-1 vaccine on insert-specific immune responses. Vaccine. 2012 Dec 17;31(1):114-9. doi: 10.1016/j.vaccine.2012.10.093. Epub 2012 Nov 7.
- Derived from this study: PubMed 21216311Keefer MC, Frey SE, Elizaga M, Metch B, De Rosa SC, Barroso PF, Tomaras G, Cardinali M, Goepfert P, Kalichman A, Philippon V, McElrath MJ, Jin X, Ferrari G, Defawe OD, Mazzara GP, Montefiori D, Pensiero M, Panicali DL, Corey L; NIAID HIV Vaccine Trials Network. A phase I trial of preventive HIV vaccination with heterologous poxviral-vectors containing matching HIV-1 inserts in healthy HIV-uninfected subjects. Vaccine. 2011 Feb 24;29(10):1948-58. doi: 10.1016/j.vaccine.2010.12.104. Epub 2011 Jan 7.
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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.
Michael Keefer, MD study chair
University of Rochester
Sharon Frey, MD study chair
St. Louis University School of Medicine
6 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 rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT), rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT) and Empty TBC-FPV in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 6 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 10 inclusion and 27 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 14 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Brazil. 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?
Safety and tolerability, as judged by local and systemic reactogenicity signs and symptoms, laboratory measures, and adverse events (time frame: After each injection and 12 months after the first injection). The study lists 2 primary outcomes in all. 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 NCT00083603, which also lists 9 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 14 Oct 2021.