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

Phase 1

Completed

• Conditions: HIV-infection

• Registration Number: NCT02413645
• Lead Sponsor: Judit Pich Martínez

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-03-30
• Study First Submitted QC: 2015-04-09
• Study First Posted: 2015-04-10
• Study Start: 2015-06
• Primary Completion: 2016-06
• Study Completion: 2016-10
• Status Verified: 2017-10
• Last Update Submitted: 2017-10-31
• Last Update Posted: 2017-11-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Dose limiting toxicity (DLT)	week 8	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

Secondary Outcome Measures

Name	Time	Method
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	week 24	Effect of vaccination on plasma viral load (pVL) (ultrasensitive assay) at screening and weeks 2, 4, 6, 8 and 24. Low-level HIV-1 viral loads will be measured using the Single copy assay (SCA). The limit of detection of the SCA will be standardized to the highest limit for any individual (0.7 copies/ml)
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.	week 24	ELISPOT assays will be performed to measure the numbers of IFN-gamma producing PBMC directed against HIV-1 sequences. Results were expressed as the number of spot-forming cells (SFC) per million of PBMC after substracting the background.
Cell-associated HIV-1 RNA (CA-RNA) quantification at week 0, 4, 6, 8 and 24	week 24	Intracellular HIV RNA species at week 0, 4, 6, 8 and 24. Cell-associated HIV-1 RNA (CA-RNA) will be isolated from cryopreserved PBMCs. CA-RNA will be quantified using a real-time PCR approach with primers/probes targeting conserved regions of the HIV long terminal repeat (LTR)/gag
Genome wide transcriptome and microRNA analysis at weeks 0 and 6	week 6	Transcriptome analysis at weeks 0 and 6 Genome wide transcriptome and microRNA analysis on the same PBMC samples will be performed. Plasma samples will be analyzed for protein expression patterns using multiplex ELISA (Luminex technology). All data will be integrated into the multidimensional database "VASP" a web based "-omics" data analysis and storage pipeline developed by Erasmus University Rotterdam to ensure data consistency and ease of analysis to all partners. Advanced bioinformatics and statistical analysis will be used to reveal the impact of vaccination on the virus-host interaction in chronic HIV infection

Trial Locations

Locations (1)

Hospital Clínic de Bacelona; 🇪🇸 Barcelona, Spain