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

NCT ID: NCT02413645

Last Updated: 2025-08-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2016-10-31

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: OTHER

TriMix_100

Intervention Type: BIOLOGICAL

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).

Group Type: OTHER

TriMix_300

Intervention Type: BIOLOGICAL

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).

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

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).

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

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).

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

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

Interventions

TriMix_100

100 μg of TriMix in

Intervention Type: BIOLOGICAL

TriMix_300

300 μg of TriMix in

Intervention Type: BIOLOGICAL

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

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

Intervention Type: BIOLOGICAL

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

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

Intervention Type: BIOLOGICAL

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

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

Intervention Type: BIOLOGICAL

Other Intervention Names

iHIVARNA-01.1; iHIVARNA-01.2; iHIVARNA-01.3

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Judit Pich Martínez

OTHER

Sponsor Role: lead

Responsible Party

Judit Pich Martínez

Clinical Research Manager

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Felipe García

Role: PRINCIPAL_INVESTIGATOR

Hospital Clinic of Barcelona

Locations

Hospital Clínic de Bacelona

Barcelona, , Spain

Countries

Spain

References

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.

Reference Type: DERIVED

PMID: 30289805 (View on PubMed)

Other Identifiers

2014-004591-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

iHIVARNA

Identifier Type: -

Identifier Source: org_study_id