HIV-infection
Conditions
Brief summary
The main purpose of the study is to evaluate the safety and to establish the recommended dose of iHIVARNA-01 as a new therapeutic vaccine against HIV
Interventions
BIOLOGICALTriMix_100
100 μg of TriMix in
BIOLOGICALTriMix_300
300 μg of TriMix in
BIOLOGICAL600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA)
600 μg of mRNA (300 μg TriMix + 300 μg HIVACAT)
BIOLOGICAL900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA)
900 μg of mRNA (300 μg TriMix + 600 μg HIVACAT)
BIOLOGICAL1200μg mRNA (900 μg HIV mRNA+300 μg TriMix mRNA)
1200 μg of mRNA (300 μg TriMix + 900 μg HIVACAT)
Sponsors
Judit Pich Martínez
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient is ≥ 18 years of age 2. Voluntarily signed informed consent 3. Patient is male, or female with negative pregnancy test prior to enrolment 4. Patient has a proven HIV-1 infection (with positive antibodies against HIV-1 and a detectable plasma HIV-1 RNA before cART) 5. Patient must be on stable treatment with cART for at least 6 months (cART is defined as an antiretroviral regimen consisting of at least three registered antiretroviral agents) 6. Nadir CD4+ cell counts must be above or equal to 350 cells/μl (1 or 2 occasional determinations below 350 will be allowed) 7. Current CD4+ cell count must be at least 450 cells/μl 8. HIV-RNA must be below 50 copies/ mL for the last 6 months prior to inclusion, during at least two measurements (occasional so called 'blips' up to 50 copies/mL are permitted)
Exclusion criteria
1. Treatment with a non-cART regimen of antiretroviral agents prior to the start of cART; 2. History of a CDC class C event (see Appendix V); 3. Patient is female and has a positive pregnancy test or the wish of pregnancy: 4. Active opportunistic infection, or any active infection or malignancy within 30 days prior to screening visit; 5. Therapy with immunomodulatory agents, including cytokines (e.g. IL2) and gamma globulin, or cytostatic chemotherapy within 90 days prior to screening visit; 6. Use of anti-coagulant medication; 7. Use of any investigational drug during the 90 days prior to study entry; 8. Previous failure to antiretroviral and/or mutations conferring genotypic resistance to antiretroviral therapy EudraCT No. 2014-004591-32 33 Protocol version 1.1, dated 10 February 2015 9. Any other condition which, in the opinion of the investigator, may interfere with the evaluation of the study objectives. 10. Active hepatitis C virus or hepatitis B virus co-infection 11. Non-subtype B HIV infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicity (DLT) | week 24 | Safety as measured by dose limiting toxicity (DLT), defined as: * Grade 3 or above local adverse event (pain, cutaneous reactions including induration) * Grade 3 or above systemic adverse event (temperature, chills, headache, nausea, vomiting, malaise, and myalgia) * Grade 3 or above other clinical or laboratory adverse event confirmed at examination or on repeat testing respectively * Any event attributable to vaccination leading to discontinuation of the immunisation regimen |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | weeks 4, 6, 8 and 24 | Changes in the magnitude of total HIV-1-specific immune response against IN peptide pools as measured by ELISPOT at baseline and weeks 4, 6, 8 and 24 Results were considered positive if the number of SFC/106 cells in stimulated wells was two-fold higher than that in unstimulated control wells, and if there were at least 50 SFC/106 cells after background subtraction. |
| Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | weeks 4, 6, 8 and 24 | Changes in the magnitude of total HIV-1-specific immune response against OUT peptide pools as measured by ELISPOT at abseline and weeks 4, 6, 8 and 24. Results were considered positive if the number of SFC/106 cells in stimulated wells was two-fold higher than that in unstimulated control wells, and if there were at least 50 SFC/106 cells after background subtraction. |
| Secondary End Point: Effect on Reservoir | weeks 4, 6, 8 and 24 | Changes from baseline in the intracelullar viral RNA copy number per million cells during and after the immunzation at week 4, 6, 8 and 24 |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 100 μg TriMix mRNA (TriMix_100) Cohort 1 (control group) 3 patients will receive 100 μg of mRNA (i.e. 100 μg TriMix mRNA).If two or more of the three patients have a dose limiting toxicity (DLT), DSMB should be consulted and study will be terminated. If one or no patients have a dose limiting toxicity, three patients will be enrolled at the next dose level.
Each patient will receive 3 immunizations (at weeks 0, 2 and 4).
TriMix\_100: 100 μg of TriMix in | 3 |
| 300 μg TriMix mRNA (TriMix_300) Cohort 2 (control group) 3 patients will receive 300 μg of mRNA (i.e. 100 μg TriMix mRNA).If two or more of the three patients have a DLT, DSMB should be consulted and study will be terminated. If one or no patients have a dose limiting toxicity, three patients will be enrolled at the next dose level.
Each patient will receive 3 immunizations (at weeks 0, 2 and 4).
TriMix\_300: 300 μg of TriMix in | 3 |
| 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) Cohort 3 (experimental group) 3 patients will receive 600 μg of mRNA (300 μg HIV mRNA + 300 μg TriMix mRNA). If two or more of the three patients have a DLT, DSMB should be consulted and study will be terminated. If one or no patients have a dose limiting toxicity, three patients will be enrolled at the next dose level.
Each patient will receive 3 immunizations (at weeks 0, 2 and 4).
600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA): 600 μg of mRNA (300 μg TriMix + 300 μg HIVACAT) | 3 |
| 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) Cohort 4 (experimental group) 3 patients will receive 900 μg of mRNA (i.e. 600 μg HIV mRNA and 300 μg TriMix mRNA). If two or more of the three first patients have a DLT, then additional three patients will be enrolled at the previous level dose (dose will be reduced to 600 μg of mRNA per vaccination). If one or no patients have a DLT, additional three patients will be enrolled at 900 μg dose level. If two or more of the six patients receiving 900 μg of mRNA have a DLT, then additional 3 patients will be enrolled at the previous level dose (dose will be reduced to 600 μg of mRNA per vaccination). If one or no patients of the six patients have a DLT, six patients will be enrolled at the next dose level.
Each patient will receive 3 immunizations (at weeks 0, 2 and 4).
900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA): 900 μg of mRNA (300 μg TriMix + 600 μg HIVACAT) | 6 |
| 1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) Cohort 5 (experimental group) 6 patients will receive 1200 μg of mRNA (i.e. 900 μg HIV mRNA + 300 μg TriMix mRNA) in case one or no patients of the six patients at the previous dose level have a DLT.
Each patient will receive 3 immunizations (at weeks 0, 2 and 4).
1200μg mRNA (900 μg HIV mRNA+300 μg TriMix mRNA): 1200 μg of mRNA (300 μg TriMix + 900 μg HIVACAT) | 6 |
| Total | 21 |
Baseline characteristics
| Characteristic | 300 μg TriMix mRNA (TriMix_300) | 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) | 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) | 100 μg TriMix mRNA (TriMix_100) | 1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 6 Participants | 3 Participants | 6 Participants | 21 Participants |
| Age, Continuous | 51 years | 45 years | 55 years | 48 years | 47 years | 51 years |
| Region of Enrollment Spain | 3 participants | 3 participants | 6 participants | 3 participants | 6 participants | 21 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 5 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 6 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 2 / 3 | 4 / 6 | 3 / 6 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Dose Limiting Toxicity (DLT)
Safety as measured by dose limiting toxicity (DLT), defined as: * Grade 3 or above local adverse event (pain, cutaneous reactions including induration) * Grade 3 or above systemic adverse event (temperature, chills, headache, nausea, vomiting, malaise, and myalgia) * Grade 3 or above other clinical or laboratory adverse event confirmed at examination or on repeat testing respectively * Any event attributable to vaccination leading to discontinuation of the immunisation regimen
Time frame: week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 μg TriMix mRNA (TriMix_100) | Dose Limiting Toxicity (DLT) | 0 participants |
| 300 μg TriMix mRNA (TriMix_300) | Dose Limiting Toxicity (DLT) | 0 participants |
| 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) | Dose Limiting Toxicity (DLT) | 0 participants |
| 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) | Dose Limiting Toxicity (DLT) | 0 participants |
| 1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) | Dose Limiting Toxicity (DLT) | 0 participants |
Secondary
Secondary End Point: Effect on Reservoir
Changes from baseline in the intracelullar viral RNA copy number per million cells during and after the immunzation at week 4, 6, 8 and 24
Time frame: weeks 4, 6, 8 and 24
Population: Baseline values were normalized to 1.0 for all groups. Subsequent measurements represent fold changes relative to baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 100 μg TriMix mRNA (TriMix_100) | Secondary End Point: Effect on Reservoir | week 8 | 0.85170504 Ratio to baseline | Standard Deviation 0.59755696 |
| 100 μg TriMix mRNA (TriMix_100) | Secondary End Point: Effect on Reservoir | week 6 | 0.69999513 Ratio to baseline | Standard Deviation 0.67071396 |
| 100 μg TriMix mRNA (TriMix_100) | Secondary End Point: Effect on Reservoir | baseline | 1.0 Ratio to baseline | Standard Deviation 0 |
| 100 μg TriMix mRNA (TriMix_100) | Secondary End Point: Effect on Reservoir | week 24 | 1.83520809 Ratio to baseline | Standard Deviation 0.44289206 |
| 100 μg TriMix mRNA (TriMix_100) | Secondary End Point: Effect on Reservoir | week 4 | 1.00631482 Ratio to baseline | Standard Deviation 0.1075206 |
| 300 μg TriMix mRNA (TriMix_300) | Secondary End Point: Effect on Reservoir | baseline | 1.0 Ratio to baseline | Standard Deviation 0 |
| 300 μg TriMix mRNA (TriMix_300) | Secondary End Point: Effect on Reservoir | week 8 | 0.81154264 Ratio to baseline | Standard Deviation 0.5543859 |
| 300 μg TriMix mRNA (TriMix_300) | Secondary End Point: Effect on Reservoir | week 6 | 0.82859145 Ratio to baseline | Standard Deviation 0.38883214 |
| 300 μg TriMix mRNA (TriMix_300) | Secondary End Point: Effect on Reservoir | week 4 | 1.19031378 Ratio to baseline | Standard Deviation 0.23113804 |
| 300 μg TriMix mRNA (TriMix_300) | Secondary End Point: Effect on Reservoir | week 24 | 0.99741551 Ratio to baseline | Standard Deviation 0.12959672 |
| 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) | Secondary End Point: Effect on Reservoir | week 8 | 0.73222371 Ratio to baseline | Standard Deviation 0.40380891 |
| 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) | Secondary End Point: Effect on Reservoir | baseline | 1.0 Ratio to baseline | Standard Deviation 0 |
| 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) | Secondary End Point: Effect on Reservoir | week 4 | 1.17119845 Ratio to baseline | Standard Deviation 0.42523104 |
| 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) | Secondary End Point: Effect on Reservoir | week 6 | 0.66586182 Ratio to baseline | Standard Deviation 0.09336465 |
| 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) | Secondary End Point: Effect on Reservoir | week 24 | 0.58142711 Ratio to baseline | Standard Deviation 0.16635469 |
| 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) | Secondary End Point: Effect on Reservoir | week 8 | 1.1 Ratio to baseline | Standard Deviation 0.92490517 |
| 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) | Secondary End Point: Effect on Reservoir | baseline | 1.0 Ratio to baseline | Standard Deviation 0 |
| 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) | Secondary End Point: Effect on Reservoir | week 4 | 1.1 Ratio to baseline | Standard Deviation 0.56388583 |
| 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) | Secondary End Point: Effect on Reservoir | week 24 | 0.9 Ratio to baseline | Standard Deviation 0.3606482 |
| 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) | Secondary End Point: Effect on Reservoir | week 6 | 1.1 Ratio to baseline | Standard Deviation 0.32910834 |
| 1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) | Secondary End Point: Effect on Reservoir | baseline | 1.0 Ratio to baseline | Standard Deviation 0 |
| 1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) | Secondary End Point: Effect on Reservoir | week 4 | 0.8 Ratio to baseline | Standard Deviation 0.46580374 |
| 1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) | Secondary End Point: Effect on Reservoir | week 8 | 0.9 Ratio to baseline | Standard Deviation 0.26581174 |
| 1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) | Secondary End Point: Effect on Reservoir | week 6 | 1.5 Ratio to baseline | Standard Deviation 1.3519809 |
| 1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) | Secondary End Point: Effect on Reservoir | week 24 | 1.0 Ratio to baseline | Standard Deviation 0.253664 |
Secondary
Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24.
Changes in the magnitude of total HIV-1-specific immune response against IN peptide pools as measured by ELISPOT at baseline and weeks 4, 6, 8 and 24 Results were considered positive if the number of SFC/106 cells in stimulated wells was two-fold higher than that in unstimulated control wells, and if there were at least 50 SFC/106 cells after background subtraction.
Time frame: weeks 4, 6, 8 and 24
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| 100 μg TriMix mRNA (TriMix_100) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 4 (IN) | 54 Spot forming cells per million of cells | Standard Error 134 |
| 100 μg TriMix mRNA (TriMix_100) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 6 (IN) | -38 Spot forming cells per million of cells | Standard Error 33 |
| 100 μg TriMix mRNA (TriMix_100) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 8 (IN) | -25 Spot forming cells per million of cells | Standard Error 65 |
| 100 μg TriMix mRNA (TriMix_100) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 24 (IN) | 3 Spot forming cells per million of cells | Standard Error 108 |
| 300 μg TriMix mRNA (TriMix_300) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 4 (IN) | 88 Spot forming cells per million of cells | Standard Error 88 |
| 300 μg TriMix mRNA (TriMix_300) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 24 (IN) | 177 Spot forming cells per million of cells | Standard Error 148 |
| 300 μg TriMix mRNA (TriMix_300) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 6 (IN) | 69 Spot forming cells per million of cells | Standard Error 69 |
| 300 μg TriMix mRNA (TriMix_300) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 8 (IN) | 105 Spot forming cells per million of cells | Standard Error 105 |
| 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 24 (IN) | -32 Spot forming cells per million of cells | Standard Error 16 |
| 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 6 (IN) | 37 Spot forming cells per million of cells | Standard Error 101 |
| 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 8 (IN) | 256 Spot forming cells per million of cells | Standard Error 148 |
| 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 4 (IN) | 140 Spot forming cells per million of cells | Standard Error 156 |
| 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 4 (IN) | -4 Spot forming cells per million of cells | Standard Error 76 |
| 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 6 (IN) | -38 Spot forming cells per million of cells | Standard Error 126 |
| 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 24 (IN) | -10 Spot forming cells per million of cells | Standard Error 75 |
| 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 8 (IN) | 60 Spot forming cells per million of cells | Standard Error 78 |
| 1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 24 (IN) | -21 Spot forming cells per million of cells | Standard Error 114 |
| 1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 8 (IN) | 173 Spot forming cells per million of cells | Standard Error 132 |
| 1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 6 (IN) | -28 Spot forming cells per million of cells | Standard Error 61 |
| 1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 4 (IN) | -106 Spot forming cells per million of cells | Standard Error 58 |
Secondary
Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24.
Changes in the magnitude of total HIV-1-specific immune response against OUT peptide pools as measured by ELISPOT at abseline and weeks 4, 6, 8 and 24. Results were considered positive if the number of SFC/106 cells in stimulated wells was two-fold higher than that in unstimulated control wells, and if there were at least 50 SFC/106 cells after background subtraction.
Time frame: weeks 4, 6, 8 and 24
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| 100 μg TriMix mRNA (TriMix_100) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 4 (OUT) | 327 Spot forming cells per million of cells | Standard Error 555 |
| 100 μg TriMix mRNA (TriMix_100) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 6 (OUT) | -226 Spot forming cells per million of cells | Standard Error 176 |
| 100 μg TriMix mRNA (TriMix_100) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 8 (OUT) | 16 Spot forming cells per million of cells | Standard Error 246 |
| 100 μg TriMix mRNA (TriMix_100) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 24 (OUT) | 3 Spot forming cells per million of cells | Standard Error 226 |
| 300 μg TriMix mRNA (TriMix_300) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 4 (OUT) | 76 Spot forming cells per million of cells | Standard Error 191 |
| 300 μg TriMix mRNA (TriMix_300) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 24 (OUT) | 375 Spot forming cells per million of cells | Standard Error 314 |
| 300 μg TriMix mRNA (TriMix_300) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 6 (OUT) | 203 Spot forming cells per million of cells | Standard Error 224 |
| 300 μg TriMix mRNA (TriMix_300) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 8 (OUT) | -34 Spot forming cells per million of cells | Standard Error 300 |
| 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 24 (OUT) | 81 Spot forming cells per million of cells | Standard Error 50 |
| 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 6 (OUT) | 138 Spot forming cells per million of cells | Standard Error 168 |
| 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 8 (OUT) | 377 Spot forming cells per million of cells | Standard Error 176 |
| 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 4 (OUT) | 379 Spot forming cells per million of cells | Standard Error 27 |
| 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 4 (OUT) | 135 Spot forming cells per million of cells | Standard Error 383 |
| 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 6 (OUT) | 10 Spot forming cells per million of cells | Standard Error 285 |
| 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 24 (OUT) | 100 Spot forming cells per million of cells | Standard Error 350 |
| 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 8 (OUT) | 596 Spot forming cells per million of cells | Standard Error 593 |
| 1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 24 (OUT) | -42 Spot forming cells per million of cells | Standard Error 124 |
| 1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 8 (OUT) | 17 Spot forming cells per million of cells | Standard Error 129 |
| 1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 6 (OUT) | 1 Spot forming cells per million of cells | Standard Error 73 |
| 1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) | Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24. | Week 4 (OUT) | -357 Spot forming cells per million of cells | Standard Error 124 |