Clinical trial NCT02413645: A Phase I, Open Label Dose Escalation Study to Evaluate Safety of iHIVARNA-01 in Chronically HIV-infected Patients Under Stable Combined Antiretroviral Therapy
Official title: A Phase I, Open Label Dose Escalation Study to Evaluate Safety of iHIVARNA-01 in Chronically HIV-infected Patients Under Stable Combined Antiretroviral Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV-infection
Lead sponsor: Fundacion Clinic per a la Recerca Biomédica
Sponsor class: OTHER
First posted: 2015-04-10
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The mai 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


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

Primary outcomes:
measure: Dose limiting toxicity (DLT)
timeFrame: week 8
Secondary outcomes:
measure: Immunogenicity (number of spot-forming cells (SFC) per million of IFN-gamma producing PBMC directed against HIV-1 sequences) as measured by ELISPOT at baseline and weeks 4, 6, 8 and 24.
timeFrame: week 24
measure: Effect of vaccination on plasma viral load (pVL) (ultrasensitive assay) using the Single copy assay (SCA) at screening and weeks 2, 4, 6, 8 and 24
timeFrame: week 24
measure: Cell-associated HIV-1 RNA (CA-RNA) quantification at week 0, 4, 6, 8 and 24
timeFrame: week 24
measure: Genome wide transcriptome and microRNA analysis at weeks 0 and 6
timeFrame: week 6
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clínic de Bacelona
Study officials:
affiliation: Hospital Clinic of Barcelona
name: Felipe García
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.