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

NCT02413645 | Completed Phase 1 Results DMC

• 2 other identifiers: iHIVARNA2014-004591-32
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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

Conditions

HIV-infection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

• 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

• Secondary End Point: Effect on Reservoir

  weeks 4, 6, 8 and 24

Study Arms (5)

100 μg TriMix mRNA (TriMix_100)

OTHER

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

300 μg TriMix mRNA (TriMix_300)

OTHER

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

600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA)

EXPERIMENTAL

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)

900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA)

EXPERIMENTAL

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)

1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA)

EXPERIMENTAL

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)

Interventions

TriMix_100 BIOLOGICAL

100 μg of TriMix in

100 μg TriMix mRNA (TriMix_100)

TriMix_300 BIOLOGICAL

300 μg of TriMix in

300 μg TriMix mRNA (TriMix_300)

600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) BIOLOGICAL

600 μg of mRNA (300 μg TriMix + 300 μg HIVACAT)

Also known as: iHIVARNA-01.1

600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA)

900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) BIOLOGICAL

900 μg of mRNA (300 μg TriMix + 600 μg HIVACAT)

Also known as: iHIVARNA-01.2

900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA)

1200μg mRNA (900 μg HIV mRNA+300 μg TriMix mRNA) BIOLOGICAL

1200 μg of mRNA (300 μg TriMix + 900 μg HIVACAT)

Also known as: iHIVARNA-01.3

1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is ≥ 18 years of age
• Voluntarily signed informed consent
• Patient is male, or female with negative pregnancy test prior to enrolment
• Patient has a proven HIV-1 infection (with positive antibodies against HIV-1 and a detectable plasma HIV-1 RNA before cART)
• 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)
• Nadir CD4+ cell counts must be above or equal to 350 cells/μl (1 or 2 occasional determinations below 350 will be allowed)
• Current CD4+ cell count must be at least 450 cells/μl

You may not qualify if:

• Treatment with a non-cART regimen of antiretroviral agents prior to the start of cART;
• History of a CDC class C event (see Appendix V);
• Patient is female and has a positive pregnancy test or the wish of pregnancy:
• Active opportunistic infection, or any active infection or malignancy within 30 days prior to screening visit;
• Therapy with immunomodulatory agents, including cytokines (e.g. IL2) and gamma globulin, or cytostatic chemotherapy within 90 days prior to screening visit;
• Use of anti-coagulant medication;
• Use of any investigational drug during the 90 days prior to study entry;
• 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
• Any other condition which, in the opinion of the investigator, may interfere with the evaluation of the study objectives.
• Active hepatitis C virus or hepatitis B virus co-infection
• Non-subtype B HIV infection

Sponsors & Collaborators

• Judit Pich Martínez: lead

Study Sites (1)

Hospital Clínic de Bacelona

Barcelona, 08036, Spain

Location

Related Publications (1)

• 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.

  PMID: 30289805 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

RNA, Messenger

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

RNA; Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

There was an error in the study product, see: https://insights.ovid.com/pubmed?pmid=31490219

Results Point of Contact

• Title: Dr. Felipe Garcia
• Organization: Hospital Clinic-HIVACAT

fgarcia@clinic.cat

932275400

Study Officials

• Felipe García

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Research Manager

Study Record Dates

• First Submitted: March 30, 2015
• First Posted: April 10, 2015
• Study Start: June 1, 2015
• Primary Completion: June 1, 2016
• Study Completion: October 1, 2016
• Last Updated: August 22, 2025
• Results First Posted: August 22, 2025

Record last verified: 2025-08

Locations

ES (1)