Trial Outcomes & Findings for Phase I, Open Label Dose Escalation Study to Evaluate Safety of iHIVARNA-01 in Chronically HIV-infected Patients (NCT NCT02413645)

Last Updated: 2025-08-22

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

21 participants

Primary outcome timeframe

week 24

Results posted on

2025-08-22

Participant Flow

Participant milestones

Participant milestones
Measure	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	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	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)	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)	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)
Overall Study STARTED	3	3	3	6	6
Overall Study COMPLETED	3	3	3	6	6
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase I, Open Label Dose Escalation Study to Evaluate Safety of iHIVARNA-01 in Chronically HIV-infected Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	100 μg TriMix mRNA (TriMix_100) n=3 Participants 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	300 μg TriMix mRNA (TriMix_300) n=3 Participants 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	600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) n=3 Participants 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)	900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) n=6 Participants 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)	1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) n=6 Participants 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)	Total n=21 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants	6 Participants n=21 Participants	21 Participants n=8 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Age, Continuous	48 years n=5 Participants	51 years n=7 Participants	45 years n=5 Participants	55 years n=4 Participants	47 years n=21 Participants	51 years n=8 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	0 Participants n=21 Participants	5 Participants n=8 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants	6 Participants n=21 Participants	16 Participants n=8 Participants
Region of Enrollment Spain	3 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	6 participants n=4 Participants	6 participants n=21 Participants	21 participants n=8 Participants

PRIMARY outcome

Timeframe: week 24

Outcome measures

Outcome measures
Measure	100 μg TriMix mRNA (TriMix_100) n=3 Participants 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	300 μg TriMix mRNA (TriMix_300) n=3 Participants 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	600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) n=3 Participants 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)	900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) n=3 Participants 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)	1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) n=6 Participants 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)
Dose Limiting Toxicity (DLT)	0 participants	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	100 μg TriMix mRNA (TriMix_100) n=3 Participants 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	300 μg TriMix mRNA (TriMix_300) n=3 Participants 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	600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) n=3 Participants 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)	900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) n=6 Participants 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)	1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) n=6 Participants 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)
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	88 Spot forming cells per million of cells Standard Error 88	140 Spot forming cells per million of cells Standard Error 156	-4 Spot forming cells per million of cells Standard Error 76	-106 Spot forming cells per million of cells Standard Error 58
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	69 Spot forming cells per million of cells Standard Error 69	37 Spot forming cells per million of cells Standard Error 101	-38 Spot forming cells per million of cells Standard Error 126	-28 Spot forming cells per million of cells Standard Error 61
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	105 Spot forming cells per million of cells Standard Error 105	256 Spot forming cells per million of cells Standard Error 148	60 Spot forming cells per million of cells Standard Error 78	173 Spot forming cells per million of cells Standard Error 132
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	177 Spot forming cells per million of cells Standard Error 148	-32 Spot forming cells per million of cells Standard Error 16	-10 Spot forming cells per million of cells Standard Error 75	-21 Spot forming cells per million of cells Standard Error 114

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	100 μg TriMix mRNA (TriMix_100) n=3 Participants 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	300 μg TriMix mRNA (TriMix_300) n=3 Participants 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	600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) n=3 Participants 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)	900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) n=6 Participants 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)	1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA) n=6 Participants 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)
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	76 Spot forming cells per million of cells Standard Error 191	379 Spot forming cells per million of cells Standard Error 27	135 Spot forming cells per million of cells Standard Error 383	-357 Spot forming cells per million of cells Standard Error 124
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	203 Spot forming cells per million of cells Standard Error 224	138 Spot forming cells per million of cells Standard Error 168	10 Spot forming cells per million of cells Standard Error 285	1 Spot forming cells per million of cells Standard Error 73
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	-34 Spot forming cells per million of cells Standard Error 300	377 Spot forming cells per million of cells Standard Error 176	596 Spot forming cells per million of cells Standard Error 593	17 Spot forming cells per million of cells Standard Error 129
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	375 Spot forming cells per million of cells Standard Error 314	81 Spot forming cells per million of cells Standard Error 50	100 Spot forming cells per million of cells Standard Error 350	-42 Spot forming cells per million of cells Standard Error 124

SECONDARY outcome

Timeframe: 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.

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