Evaluating a Combination of Immune-based Therapies to Achieve a Remission of HIV Infection

NCT03619278 | Withdrawn Phase 1 DMC

• 1 other identifier: 2017-000566-30
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

A phase I/IIa, multinational, multicentric (IDIBAPS, IRSICAIXA, AARHUS, VUB, APHP), randomised, balanced by centre (to include participants from the 4 arms), open-label, controlled clinical trial. Each participant will be followed up a different time according to study arm: a minimum of 38 weeks in arm I, 31 weeks in arm II, 54 weeks in arm III and 26 weeks in the arm 4. The study duration will be 104 weeks from inclusion of the first participant. Participants will be randomised to one of the following 4 arms:

• Arm 1 (study): 14 participants will receive 3 vaccines of HIVARNA01.3 prime, 2 MVA-vectored vaccine boosts, 1 dose of 10-1074 antibodies and 3 doses of romidepsin
• Arm 2 (study): 14 participants will receive 5 vaccines of HIVARNA01.3, 1 dose of 10-1074 antibodies and 3 doses of romidepsin
• Arm 3 (study): 14 participants will receive 5 vaccines of personalized RNA vaccine (HIVACAR01), 1 dose of 10-1074 antibodies and 3 doses of romidepsin
• Arm 4 (control): 14 participants 1 dose of 10-1074 antibodies and 3 doses of romidepsin

Conditions

HIV Infections

Keywords

HIV

Outcome Measures

Primary Outcomes (1)

• Grade 3 or above severe local , systemic, clinical or laboratory adverse event t

  Local adverse events may be pain, cutaneous reactions including induration and systemic emperature, chills, headache, nausea, vomiting, malaise, and myalgia. Clinical and laboratory must be confirmed at examination or on repeat testing respectively. Any adverse event attributable to the combination therapy leading to discontinuation of the study treatmen

  12 days (28 days after each inmuisation)

Secondary Outcomes (22)

• Proportion of participants who maintain an undetectable viral load

  12 weeks (after discontinuation of antiretroviral therapy)

• Percentage of participants with control of viral load below detectable level

  24 weeks (after discontinuation of antiretroviral therapy)

• Change from baseline in total proviral HIV-1 DNA per 10^6 CD4+ T cells.

  up to 51 weeks

• Change from baseline in integrated proviral HIV-1 DNA per 10^6 CD4+ T cells.

  up to 51 weeks

• Change from baseline in HIV-1 transcription.

  up to 39 weeks

Study Arms (2)

HIVACAR

EXPERIMENTAL

Participants will receive 5 vaccines of personalized RNA vaccine (HIVACAR01), 2 dose of 10-1074 antibodies and 3 doses of romidepsin

Other: HIVACAR

Placebo

PLACEBO COMPARATOR

Participants will receive 5 doses of placebo, 2 doses of 10-1074 antibodies and 3 doses of romidepsin

Other: placebo

Interventions

HIVACAR OTHER

Participants will receive 5 vaccines of personalized RNA vaccine (HIVACAR01), 2 doses of 10-1074 antibodies and 3 doses of romidepsin

HIVACAR

placebo OTHER

Participants will receive 5 vaccines of placebo of HIVACAR01, 2 doses of 10-1074 antibodies and 3 doses of romidepsin

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Between ≥ 18 to \<60 years of age
• Voluntarily signed informed consent
• Male, or female with negative pregnancy test prior to enrolment
• Proven HIV-1 infection (with positive antibodies against HIV-1 and a detectable plasma HIV-1 RNA before cART)
• Must be on stable treatment with cART for at least 18 months (cART is defined as an antiretroviral regimen consisting of at least three registered antiretroviral agents; periods of mono/dual antiretroviral therapy if not first time therapy and confirmed viral suppression during these periods of mono/dual therapy are permitted)
• Nadir CD4+ cell counts must be above or equal to 350 cells/µl, 2-3 occasional determinations below 350 cells/μl are allowed.
• Current CD4+ cell count must be at least 450 cells/µl
• If male or female of childbearing potential willing to take correct contraceptive measures:
• If heterosexually active female; using an effective method of contraception from 14 days prior to the first vaccination until at least 12 weeks after the last vaccination; all female volunteers must be willing to undergo urine or serum pregnancy tests at time points specified in the Schedule of Procedures.
• If heterosexually active male; willing to use an effective method of contraception or agree on the use of an effective method of contraception by his partner from the day of the first vaccination until 12 weeks after the last vaccination.
• If sexually active, willing to use a reliable method of reducing the risk of transmission to their sexual partners during treatment interruption (which could include pre-exposure prophylaxis \[PrEP\] for their sexual partners)

You may not qualify if:

• Treatment with a non-cART regimen of antiretroviral agents prior to the start of any antiretroviral regimen
• History of a CDC class C event (see Appendix IV)
• Women of childbearing potential with a positive pregnancy test, or participants (male or female) who wish to plan a pregnancy during the trial period.
• 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 antiretroviral therapy failure and/or mutations conferring genotypic resistance to antiretroviral therapy
• Participants with severe cardiovascular diseases or long QT interval
• Active hepatitis C virus
• Hepatitis B infection
• Treatment with strong inhibitors or inducers of CYP3A4, except protease inhibitors for HIV treatment (see protocol section 5.7); if in treatment of protease inhibitors for HIV not willing to change inhibitor protease for an integrase inhibitor during the study.
• Any known allergy or intolerance to any of the study drugs or excipient
• Protein egg allergy
• Known past history of clinical Epstein-Barr Virus (EBV) infection or recurrent herpes zoster

Sponsors & Collaborators

• Judit Pich: lead

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Research Manager

Study Record Dates

• First Submitted: March 14, 2018
• First Posted: August 7, 2018
• Study Start: November 1, 2020
• Primary Completion: July 15, 2021
• Study Completion: July 15, 2021
• Last Updated: September 11, 2025

Record last verified: 2025-09