HIV Infection
Conditions
Brief summary
The development of a safe and effective HIV-1 vaccine strategy would probably be the best solution for the ultimate control of the worldwide AIDS pandemic. Heterologous prime-boost immunisations are today considered promising HIV prophylactic vaccine strategies. It is thus relevant to pursue the development of different candidate vaccines in prime-boost vaccine strategies to identify the most promising prime-boost combinations and to integrate scientific inquiry into trial protocols from the beginning to maximize learning opportunities.
Detailed description
Phase I/II, multicenter, national, open-label, randomized trial HIV including 4 prophylactic prime-boost HIV vaccines strategies: Volunteers are randomly allocated in a 1:1:1:1 ratio at trial entry to 4 parallel arms with the following prime-boost strategies: Arm 1. MVA HIV-B primes at Week 0 and Week 8 + LIPO-5 boosts at Week 20 and Week 28 Arm 2. LIPO-5 primes at Week 0 and Week 8 + MVA HIV-B boosts at Week 20 and Week 28 Arm 3. GTU-MultiHIV B primes at Week 0, Week 4 and Week 12 + LIPO-5 boosts at Week 20 and Week 28 Arm 4. GTU-MultiHIV B primes at Week 0, Week 4 and Week 12 + MVA HIV-B boosts at Week 20 and Week 28
Interventions
BIOLOGICALLIPO-5
LIPO-5: 1mL IntraMuscular, 2 shots;
BIOLOGICALMVA HIV-B (MVATG17401)
MVA HIV-B (MVATG17401): 0.5mL IntraMuscular, 2 shots;
BIOLOGICALGTU®-MultiHIV B: 0.5 mL IM via Biojector® 2000 and 0.5mL IntraDermic, 3 shots
GTU®-MultiHIV B: 0.5 mL IM via Biojector® 2000 and 0.5mL IntraDermic, 3 shots
Sponsors
ANRS, Emerging Infectious Diseases
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Written and signed informed consent * Subject at low risk to contract HIV i.e. * no history of injecting drug use in the previous ten years; * no gonorrhea or syphilis in the last six months; * no high risk partner (e.g. injecting drug user, HIV positive partner) either currently or within the past six months ; * no unprotected anal intercourse in the last six months, outside a relationship with a regular partner known/presumed to be HIV negative ; * no unprotected vaginal intercourse in the last six months outside a relationship with a regular known/presumed HIV negative partner * Available for follow-up for the duration of the study (56 weeks from screening) * Willing to undergo a HIV test * Willing to undergo a genital infection screen * If heterosexually active female, using an effective method of contraception with partner (combined oral contraceptive pill; injectable contraceptive; contraceptive implant/patch; IntraUterine Contraceptive Device (IUCD); consistent record with condoms if using these; physiological or anatomical sterility in self or partner) from 14 days prior to the first vaccination until 4 months after the last, and willing to undergo urine pregnancy tests prior to each vaccination * If heterosexually active male, using an effective method of contraception with their partner from the first day of vaccination until 4 months after the last vaccination * Subject registered in French Health ministry computerised file and authorised to participate in a clinical trial * Subject covered by Health Insurance
Exclusion criteria
* Clinically relevant abnormality on history or examination including history of: * uncontrolled infection; * autoimmune disease; * immunodeficiency or use of immunosuppressive drugs within 3 months prior to screening; * cancer; * chronic diseases requiring long-term treatment whose interruption during the trial has no impact on the health status in the short or long-term * Receipt of live attenuated vaccine within 60 days or other vaccine within 14 days prior to W0 * Planned receipt of other vaccines than those planned by the protocol and those recommended in France (excluding live attenuated vaccines) during the trial follow-up (reference : Weekly Epidemiological Newsletter 14-15 dated on April 10th, 2012 (Bulletin Epidémiologique hebdomadaire 14-15 / 10 avril 2012)) * Receipt of blood products or immunoglobin within 4 months prior to screening * History of severe local or general reaction to vaccination defined as * local: extensive, indurated redness and swelling involving most of the antero-lateral thigh or the major circumference of the arm, not resolving within 72 hours * general: fever ≥ 39.5°C within 48 hours; anaphylaxis; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours * Positive for ANA antibodies at a titer considered clinically significant: titer ≥ local cut-off associated with positive anti-native DNA and extractable nuclear antigen antibodies * HIV-1 or HIV-2 positive or indeterminate at screening * Woman expecting to conceive during the study period * Pregnant or breastfeeding woman * Symptoms, physical signs or laboratory values suggestive of systemic disorders, including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric, which could interfere with the interpretation of the trial results or compromise the health of the volunteers * Clinically significant grade 1 routine laboratory parameters * Grade 2 or above routine laboratory parameters * Known hypersensitivity to aminoglycosides and eggs (as used in the vaccine production processes) * Known hypersensitivity to one of the trial vaccine components, the metabolites or formulation excipients * Anticipated non-compliance with the protocol * Participation in another clinical trial with an on-going exclusion period at screening * Participation in a HIV preventive vaccine clinical trial (unless participant were randomized in placebo arm) * Subject under legal guardianship or incapacitation * Subject who is an active blood donor and unwilling to interrupt blood donations during the his/her participation in the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the Safety of MVA HIV-B at Week 2 in Arm 1 | Visit Week 2 | Count of participants without any grade 3 or 4 adverse events (clinical or biological) related to MVA-vaccine immunisation, reported from Week 0 to Week 2 in arm 1 |
| To Discard Vaccine Strategies With an Insufficient Level of Immunogenicity, Defined by HIV-specific IFN-γ-ELISPOT Responses, Among 4 HIV Prophylactic Prime-boost Combinations in Healthy Volunteers at Low Risk of HIV Infection | Visit Week 30 | Count of participants with a HIV-specific Interferon-gamma Enzyme Linked Immunosorbent SPOT (IFN-γ ELISPOT) response in each of the 4 arms, defined by a positive response to at least one of the stimulating HIV peptide pools (15-mer pools covering Env, Gag, Pol, and Nef) measured in stimulated Peripheral Blood Mononuclear Cell (PBMC) by a standard IFN-γ ELISPOT assay at Week 30, i.e. 2 weeks after the last vaccine immunisation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Assess the Tolerance of Each Prime-boost Combination | Between week 0 and week 52 | Count of participants with at least one clinical/biological AE/SAE related to vaccine immunisation. |
| To Assess for Each Prime-boost Combination the Type of Vaccine-induced T Cell Response | At W2, W10 and W22 for reporting groups : MVA HIV-B/LIPO-5 and LIPO-5/MVA HIV-B. And at W2, W6, W14 and W22 for reporting groups : GTU-MultiHIV B/LIPO-T and GTU-MultiHIV B/MVA HIV-B. | In all participants having received at least 1 dose of vaccine, the count of participants with HIV-specific ELISPOT response to at least one of stimulating HIV peptide pools. |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORJean-Daniel LELIEVRE Study Chair, Pr
Hopital Henri Mondor
PRINCIPAL_INVESTIGATORLaura RICHERT Methodologist, Dr
Inserm Unit 897
Participant flow
Recruitment details
Healthy volunteers will be recruited through the ARNS network of volunteers, through advertising via media and through a dedicated website, and given a telephone number to contact. From March 2014 to March 2015, 129 participants were screened in four sites in France.
Participants by arm
| Arm | Count |
|---|---|
| MVA HIV-B/LIPO-5 MVA HIV-B primes 0,5mL IntraMuscular at W0 and W8 LIPO-5 1mL IntraMuscular boosts at W20 and W28 | 23 |
| LIPO-5/MVA HIV-B LIPO-5 primes 1mL IntraMuscular at W0 and W8 MVA HIV-B 0,5mL IntraMuscular boosts at W20 and W28 | 23 |
| GTU-MultiHIV B/LIPO-5 GTU-MultiHIV B 0,5mL IntraMuscular via Biojector 2000 and 0,5mL IntraDermic primes at W0, W4 and W12 LIPO-5 1mL IntraMuscular boosts at W20 and W28 | 23 |
| GTU-MultiHIV B/MVA HIV-B GTU-MultiHIV B 0,5mL IntraMuscular via Biojector 2000 and 0,5mL IntraDermic primes at W0, W4 and W12 MVA HIV-B 0,5mL IntraMuscular boosts at W20 and W28 | 23 |
| Total | 92 |
Baseline characteristics
| Characteristic | LIPO-5/MVA HIV-B | GTU-MultiHIV B/LIPO-5 | MVA HIV-B/LIPO-5 | GTU-MultiHIV B/MVA HIV-B | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 23 Participants | 23 Participants | 23 Participants | 92 Participants |
| Age, Continuous | 24 years | 29 years | 26 years | 26 years | 27 years |
| Region of Enrollment France | 23 participants | 23 participants | 23 participants | 23 participants | 92 participants |
| Sex: Female, Male Female | 11 Participants | 9 Participants | 8 Participants | 14 Participants | 42 Participants |
| Sex: Female, Male Male | 12 Participants | 14 Participants | 15 Participants | 9 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 22 / 23 | 23 / 23 | 22 / 23 | 23 / 23 |
| serious Total, serious adverse events | 3 / 23 | 5 / 23 | 7 / 23 | 3 / 23 |
Outcome results
Primary
Evaluation of the Safety of MVA HIV-B at Week 2 in Arm 1
Count of participants without any grade 3 or 4 adverse events (clinical or biological) related to MVA-vaccine immunisation, reported from Week 0 to Week 2 in arm 1
Time frame: Visit Week 2
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MVA HIV-B/LIPO-5 | Evaluation of the Safety of MVA HIV-B at Week 2 in Arm 1 | 22 Participants |
Primary
To Discard Vaccine Strategies With an Insufficient Level of Immunogenicity, Defined by HIV-specific IFN-γ-ELISPOT Responses, Among 4 HIV Prophylactic Prime-boost Combinations in Healthy Volunteers at Low Risk of HIV Infection
Count of participants with a HIV-specific Interferon-gamma Enzyme Linked Immunosorbent SPOT (IFN-γ ELISPOT) response in each of the 4 arms, defined by a positive response to at least one of the stimulating HIV peptide pools (15-mer pools covering Env, Gag, Pol, and Nef) measured in stimulated Peripheral Blood Mononuclear Cell (PBMC) by a standard IFN-γ ELISPOT assay at Week 30, i.e. 2 weeks after the last vaccine immunisation.
Time frame: Visit Week 30
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MVA HIV-B/LIPO-5 | To Discard Vaccine Strategies With an Insufficient Level of Immunogenicity, Defined by HIV-specific IFN-γ-ELISPOT Responses, Among 4 HIV Prophylactic Prime-boost Combinations in Healthy Volunteers at Low Risk of HIV Infection | 7 Participants |
| LIPO-5/MVA HIV-B | To Discard Vaccine Strategies With an Insufficient Level of Immunogenicity, Defined by HIV-specific IFN-γ-ELISPOT Responses, Among 4 HIV Prophylactic Prime-boost Combinations in Healthy Volunteers at Low Risk of HIV Infection | 9 Participants |
| GTU-MultiHIV B/LIPO-5 | To Discard Vaccine Strategies With an Insufficient Level of Immunogenicity, Defined by HIV-specific IFN-γ-ELISPOT Responses, Among 4 HIV Prophylactic Prime-boost Combinations in Healthy Volunteers at Low Risk of HIV Infection | 0 Participants |
| GTU-MultiHIV B/MVA HIV-B | To Discard Vaccine Strategies With an Insufficient Level of Immunogenicity, Defined by HIV-specific IFN-γ-ELISPOT Responses, Among 4 HIV Prophylactic Prime-boost Combinations in Healthy Volunteers at Low Risk of HIV Infection | 14 Participants |
Comparison: Trial was designed to compare the observed proportion of responders at week 30 within each group to a predefined minimum immunogenicity level of 50%.p-value: =0.02Binomial
Secondary
To Assess for Each Prime-boost Combination the Type of Vaccine-induced T Cell Response
In all participants having received at least 1 dose of vaccine, the count of participants with HIV-specific ELISPOT response to at least one of stimulating HIV peptide pools.
Time frame: At W2, W10 and W22 for reporting groups : MVA HIV-B/LIPO-5 and LIPO-5/MVA HIV-B. And at W2, W6, W14 and W22 for reporting groups : GTU-MultiHIV B/LIPO-T and GTU-MultiHIV B/MVA HIV-B.
Population: The number of participants differs due to the unavailability of some participants for some of the visits planned.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MVA HIV-B/LIPO-5 | To Assess for Each Prime-boost Combination the Type of Vaccine-induced T Cell Response | Week 2 | 5 Participants |
| MVA HIV-B/LIPO-5 | To Assess for Each Prime-boost Combination the Type of Vaccine-induced T Cell Response | Week 10 | 13 Participants |
| MVA HIV-B/LIPO-5 | To Assess for Each Prime-boost Combination the Type of Vaccine-induced T Cell Response | Week 22 | 9 Participants |
| LIPO-5/MVA HIV-B | To Assess for Each Prime-boost Combination the Type of Vaccine-induced T Cell Response | Week 10 | 1 Participants |
| LIPO-5/MVA HIV-B | To Assess for Each Prime-boost Combination the Type of Vaccine-induced T Cell Response | Week 2 | 1 Participants |
| LIPO-5/MVA HIV-B | To Assess for Each Prime-boost Combination the Type of Vaccine-induced T Cell Response | Week 22 | 8 Participants |
| GTU-MultiHIV B/LIPO-5 | To Assess for Each Prime-boost Combination the Type of Vaccine-induced T Cell Response | Week 6 | 0 Participants |
| GTU-MultiHIV B/LIPO-5 | To Assess for Each Prime-boost Combination the Type of Vaccine-induced T Cell Response | Week 14 | 0 Participants |
| GTU-MultiHIV B/LIPO-5 | To Assess for Each Prime-boost Combination the Type of Vaccine-induced T Cell Response | Week 2 | 1 Participants |
| GTU-MultiHIV B/LIPO-5 | To Assess for Each Prime-boost Combination the Type of Vaccine-induced T Cell Response | Week 22 | 1 Participants |
| GTU-MultiHIV B/MVA HIV-B | To Assess for Each Prime-boost Combination the Type of Vaccine-induced T Cell Response | Week 6 | 1 Participants |
| GTU-MultiHIV B/MVA HIV-B | To Assess for Each Prime-boost Combination the Type of Vaccine-induced T Cell Response | Week 2 | 1 Participants |
| GTU-MultiHIV B/MVA HIV-B | To Assess for Each Prime-boost Combination the Type of Vaccine-induced T Cell Response | Week 22 | 12 Participants |
| GTU-MultiHIV B/MVA HIV-B | To Assess for Each Prime-boost Combination the Type of Vaccine-induced T Cell Response | Week 14 | 0 Participants |
Secondary
To Assess the Tolerance of Each Prime-boost Combination
Count of participants with at least one clinical/biological AE/SAE related to vaccine immunisation.
Time frame: Between week 0 and week 52
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MVA HIV-B/LIPO-5 | To Assess the Tolerance of Each Prime-boost Combination | Clinical AE related to vaccine immunisation | 22 Participants |
| MVA HIV-B/LIPO-5 | To Assess the Tolerance of Each Prime-boost Combination | Clinical SAE related to vaccine immunisation | 0 Participants |
| MVA HIV-B/LIPO-5 | To Assess the Tolerance of Each Prime-boost Combination | Biological AE related to vaccine immunisation | 1 Participants |
| MVA HIV-B/LIPO-5 | To Assess the Tolerance of Each Prime-boost Combination | Biological SAE related to vaccine immunisation | 1 Participants |
| LIPO-5/MVA HIV-B | To Assess the Tolerance of Each Prime-boost Combination | Clinical SAE related to vaccine immunisation | 0 Participants |
| LIPO-5/MVA HIV-B | To Assess the Tolerance of Each Prime-boost Combination | Biological AE related to vaccine immunisation | 0 Participants |
| LIPO-5/MVA HIV-B | To Assess the Tolerance of Each Prime-boost Combination | Biological SAE related to vaccine immunisation | 0 Participants |
| LIPO-5/MVA HIV-B | To Assess the Tolerance of Each Prime-boost Combination | Clinical AE related to vaccine immunisation | 21 Participants |
| GTU-MultiHIV B/LIPO-5 | To Assess the Tolerance of Each Prime-boost Combination | Biological AE related to vaccine immunisation | 0 Participants |
| GTU-MultiHIV B/LIPO-5 | To Assess the Tolerance of Each Prime-boost Combination | Clinical SAE related to vaccine immunisation | 2 Participants |
| GTU-MultiHIV B/LIPO-5 | To Assess the Tolerance of Each Prime-boost Combination | Biological SAE related to vaccine immunisation | 0 Participants |
| GTU-MultiHIV B/LIPO-5 | To Assess the Tolerance of Each Prime-boost Combination | Clinical AE related to vaccine immunisation | 21 Participants |
| GTU-MultiHIV B/MVA HIV-B | To Assess the Tolerance of Each Prime-boost Combination | Biological SAE related to vaccine immunisation | 1 Participants |
| GTU-MultiHIV B/MVA HIV-B | To Assess the Tolerance of Each Prime-boost Combination | Clinical SAE related to vaccine immunisation | 0 Participants |
| GTU-MultiHIV B/MVA HIV-B | To Assess the Tolerance of Each Prime-boost Combination | Clinical AE related to vaccine immunisation | 23 Participants |
| GTU-MultiHIV B/MVA HIV-B | To Assess the Tolerance of Each Prime-boost Combination | Biological AE related to vaccine immunisation | 1 Participants |