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

A Phase I, Open Label Dose Escalation Study to Evaluate Safety of iHIVARNA-01 in Chronically HIV-infected Patients Under Stable Combined Antiretroviral Therapy

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

Study Overview

• Status: Completed
• Conditions: HIV-infection
• Intervention / Treatment: Biological: TriMix_100; Biological: TriMix_300; Biological: 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA); Biological: 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA); Biological: 1200μg mRNA (900 μg HIV mRNA+300 μg TriMix mRNA)

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic de Bacelona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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).	Biological: TriMix_100; 100 μg of TriMix in
Other: 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).	Biological: TriMix_300; 300 μg of TriMix in
Experimental: 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).	Biological: 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA); 600 μg of mRNA (300 μg TriMix + 300 μg HIVACAT); Other Names: iHIVARNA-01.1
Experimental: 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).	Biological: 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA); 900 μg of mRNA (300 μg TriMix + 600 μg HIVACAT); Other Names: iHIVARNA-01.2
Experimental: 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).	Biological: 1200μg mRNA (900 μg HIV mRNA+300 μg TriMix mRNA); 1200 μg of mRNA (300 μg TriMix + 900 μg HIVACAT); Other Names: iHIVARNA-01.3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	weeks 4, 6, 8 and 24
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.	weeks 4, 6, 8 and 24
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	weeks 4, 6, 8 and 24

Collaborators and Investigators

• Sponsor: Judit Pich Martínez
• Investigators: Principal Investigator: Felipe García, Hospital Clinic of Barcelona

Publications and helpful links

General Publications

• Leal L, Guardo AC, Moron-Lopez S, Salgado M, Mothe B, Heirman C, Pannus P, Vanham G, van den Ham HJ, Gruters R, Andeweg A, Van Meirvenne S, Pich J, Arnaiz JA, Gatell JM, Brander C, Thielemans K, Martinez-Picado J, Plana M, Garcia F; iHIVARNA consortium. Phase I clinical trial of an intranodally administered mRNA-based therapeutic vaccine against HIV-1 infection. AIDS. 2018 Nov 13;32(17):2533-2545. doi: 10.1097/QAD.0000000000002026.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: March 30, 2015
• First Submitted That Met QC Criteria: April 9, 2015
• First Posted (Estimated): April 10, 2015

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections
• Other Study ID Numbers: iHIVARNA; 2014-004591-32 (EudraCT Number)