iHIVARNA Clinical Trial in HIV Infected Individuals

NCT02888756 | Terminated Phase 2 Results DMC

• 2 other identifiers: iHIVARNA phase II2016-002724-83
• Study Type: interventional
• Target: 33
• Locations: 3 countries
• Sites: 5

Brief Summary

iHIVARNA-01 is a novel therapeutic vaccine for the treatment of HIV-1-infected patients based on in vivo modification of DCs. It consists of HIVACAT-TriMix: mRNA encoding a mixture of APC activation molecules (CD40L, a constitutively active variant of TLR4 and CD70) and the HIV target antigens contained in HIVACAT to be administered through the intranodal route. iHIVARNA-01 aims to achieve the 'functional cure' of HIV infection, i.e. controlling viral replication in the absence of anti-retroviral therapy.

Conditions

HIV Infections

Keywords

Immunotherapy; mRNA; Lentivirus infection; Virus disease; Sexually transmitted disease; Immunodeficiency syndrome

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

  * 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.

  week 6

• Immunogenicity as Measured by Elispot

  Change from baseline immunogenicity as measured by ELISPOT at week 6 and 18, i.e. two weeks and 14 weeks after the last immunization compared to both control groups

  week 6 and week 18

Secondary Outcomes (10)

• Immunogenicity as Measured by Intracellular Cytokine Staining (ICS)

  week 10, 18 and 30

• Time to Viral Rebound

  week 6-18

• Change in Plasma Viral Load

  week 6-18

• Functional Cure

  week 18

• Primary Immune Response Against Vaccine

  from baseline to week 6

Study Arms (3)

iHIVARNA-01

EXPERIMENTAL

Biological: 1200μg mRNA (900 μg HIV mRNA+300 μg TriMix mRNA) 3 vaccinations, two weeks interval

Biological: iHIVARNA-01; Biological: TriMix

TriMix

ACTIVE COMPARATOR

Biological: TriMix\_300 μg TriMix mRNA 3 vaccinations, two weeks interval

Biological: TriMix

Placebo

PLACEBO COMPARATOR

Water for injection 3 vaccinations, two weeks interval

Biological: Placebo

Interventions

iHIVARNA-01 BIOLOGICAL

Therapeutic vaccination, followed by treatment interruption

Also known as: HIVACAT, TriMix

iHIVARNA-01

TriMix BIOLOGICAL

Therapeutic vaccination, followed by treatment interruption

TriMix; iHIVARNA-01

Placebo BIOLOGICAL

Therapeutic vaccination, followed by treatment interruption

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years of age;
• Voluntarily signed informed consent;
• Proven HIV-1 infection (with documented antibodies against HIV-1 and a detectable plasma HIV-1 RNA before initiation of therapy);
• On stable treatment with cART regimen (antiretroviral therapy consisting of at least three registered antiretroviral agents) for at least 3 years;
• Nadir CD4+ ≥ 350 cells/μl (up to 2 occasional determinations ≤ 350 cells/μl are allowed);
• Current CD4+ cell count ≥ 450 cells/μl;
• HIV-RNA below 50 copies/mL in the last 6 months prior to randomization, during at least two measurements (occasional so called 'blips' ≤ 500 copies/mL are permitted);
• If sexually active, willing to use a reliable method of reducing the risk of transmission to their sexual partners during treatment interruption (including PrEP).
• For heterosexually active female, using an effective method of contraception with partner (combined oral contraceptive pill; injectable or implanted contraceptive; IUD/IUS; consistent record with condoms; physiological or anatomical sterility (in self or partner) from 14 days prior to the first vaccination until 4 months after the last vaccination.
• For heterosexually active male, using an effective method of contraception with their partner from the first day of vaccination until 4 months after the last vaccination. -

You may not qualify if:

• Treatment with non-cART regimen prior to cART regimen;
• Previous failure to antiretroviral and/or mutations conferring genotypic resistance to antiretroviral therapy;
• Non-subtype B HIV infection;
• Active Hepatitis B virus and/or Hepatitis C virus co-infection;
• History of a CDC class C event (see appendix A);
• Pregnant female (screened with a positive pregnancy test), lactating or intending to become pregnant during the study;
• Active malignancy ≤ 30 days (extended period on the clinical assessment of the investigator) prior to screening;
• Active infection with fever (38°C or above) ≤ 10 days of screening and/or first vaccination;
• Therapy with immunomodulatory agents (e.g. systemic corticosteroids), including cytokines (e.g. IL-2), immunoglobulins and/or cytostatic chemotherapy ≤ 90 days prior to screening. This does not include seasonal influenza, hepatitis B and/or other travel related vaccines;
• Congenital, acquired or induced coagulation disorders, such as thrombocytopenia (thrombocytes \< 150x109/L) and/or current use of anti-coagulant medication (e.g. coumarins, inhibitors of Xa); Usage of NSAIDs (including acetylsalicylic acid) is allowed, however it is advised to interrupt therapy 10 days ahead of vaccination;
• Usage of any investigational drug ≤ 90 days prior to study entry;
• An employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, or is a family member of an employee or the investigator Any other condition, which, in the opinion of the investigator, may interfere with the evaluation of the study objectives

Sponsors & Collaborators

• Rob Gruters: lead
• Institut d'Investigacions Biomèdiques August Pi i Sunyer: collaborator
• IrsiCaixa: collaborator
• Institute of Tropical Medicine, Belgium: collaborator
• Vrije Universiteit Brussel: collaborator
• Synapse bv: collaborator
• Asphalion: collaborator
• eTheRNA immunotherapies: collaborator
• CR2O: collaborator
• Hospital Clinic of Barcelona: collaborator
• Germans Trias i Pujol Hospital: collaborator
• Universitair Ziekenhuis Brussel: collaborator

Study Sites (5)

Institute for Tropical Medicine

Antwerp, Belgium

Location

UZ Brussel

Brussels, Belgium

Location

Erasmus MC

Rotterdam, Netherlands

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Spain

Location

Hospital Clinic

Barcelona, Spain

Location

Related Publications (1)

• de Jong W, Aerts J, Allard S, Brander C, Buyze J, Florence E, van Gorp E, Vanham G, Leal L, Mothe B, Thielemans K, Plana M, Garcia F, Gruters R; iHIVARNA consortium. iHIVARNA phase IIa, a randomized, placebo-controlled, double-blinded trial to evaluate the safety and immunogenicity of iHIVARNA-01 in chronically HIV-infected patients under stable combined antiretroviral therapy. Trials. 2019 Jun 17;20(1):361. doi: 10.1186/s13063-019-3409-1.

  PMID: 31208472 DERIVED

Related Links

• Description phase 1 clinical trial with iHIVARNA-01

MeSH Terms

Conditions

HIV Infections; Lentivirus Infections; Virus Diseases; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes

Interventions

trimix

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Retroviridae Infections; RNA Virus Infections; Genital Diseases; Urogenital Diseases; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Limited number of subjects for statistical analysis due to early termination. There was an error in the study product, see https://insights.ovid.com/pubmed?pmid=31490219

Results Point of Contact

• Title: Dr R.A. Gruters
• Organization: Erasmus MC

r.gruters@erasmusmc.nl

+31 10 7032100

Study Officials

• Rob A Gruters, PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Workgroup leader

Study Record Dates

• First Submitted: August 23, 2016
• First Posted: September 5, 2016
• Study Start: April 4, 2017
• Primary Completion: February 12, 2018
• Study Completion: February 12, 2018
• Last Updated: December 23, 2019
• Results First Posted: December 9, 2019

Record last verified: 2019-12

Locations

NL (1); BE (2); ES (2)