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

Judit Pich Martínez

Status and phase: Completed; Phase 1

Conditions: HIV-infection

Treatments: Biological: 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA); Biological: TriMix_100; Biological: 1200μg mRNA (900 μg HIV mRNA+300 μg TriMix mRNA); Biological: 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA); Biological: TriMix_300

Study type: Interventional

Funder types: Other

Identifiers

NCT02413645

iHIVARNA

2014-004591-32 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment: 21 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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21 participants in 5 patient groups

100 μg TriMix mRNA (TriMix_100)

Other group

Description:

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).

Treatment:

Biological: TriMix_100

300 μg TriMix mRNA (TriMix_300)

Other group

Description:

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).

Treatment:

Biological: TriMix_300

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

Experimental group

Description:

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).

Treatment:

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

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

Experimental group

Description:

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).

Treatment:

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

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

Experimental group

Description:

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).

Treatment:

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