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iHIVARNA Clinical Trial in HIV Infected Individuals (iHIVARNA-01)

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2017 by Rob Gruters, Erasmus Medical Center
Sponsor:
Collaborators:
Institut d'Investigacions Biomèdiques August Pi i Sunyer
IrsiCaixa
Institute of Tropical Medicine, Belgium
Vrije Universiteit Brussel
Synapse bv
Asphalion
eTheRNA immunotherapies
CR2O
Hospital Clinic of Barcelona
Germans Trias i Pujol Hospital
Universitair Ziekenhuis Brussel
Information provided by (Responsible Party):
Rob Gruters, Erasmus Medical Center
ClinicalTrials.gov Identifier:
NCT02888756
First received: August 23, 2016
Last updated: August 10, 2017
Last verified: August 2017
  Purpose
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.

Condition Intervention Phase
HIV Infections Biological: iHIVARNA-01 Biological: TriMix Biological: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase IIa Randomized, Placebo Controlled, Double Blinded Study to Evaluate the Safety and Immunogenicity of iHIVARNA-01 in Chronically HIV-infected Patients Under Stable Combined Antiretroviral Therapy

Resource links provided by NLM:


Further study details as provided by Rob Gruters, Erasmus Medical Center:

Primary Outcome Measures:
  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: week 6 ]
    • 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.


  • Immunogenicity [ Time Frame: week 6 ]
    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


Secondary Outcome Measures:
  • Immunogenicity [ Time Frame: week 10, 18 and 30 ]
    o magnitude and the kinetics of the HIV-specific CD4+ and CD8+ T cell responses after immunization (ELISPOT) as defined by the increase in the number of spot forming units and if positive the number of poly-functional T cells as determined by intracellular cytokine staining, (ICS).

  • Time to viral rebound [ Time Frame: week 6-18 ]
    time until viral rebound (defined as two consecutive measurements of plasma viral load > 1000 copies/mL separated by at least 15 days) after discontinuation at week 6.

  • Plasma viral load [ Time Frame: week 6-18 ]
    plasma viral load in vivo after ATI, week 6-18

  • Functional cure [ Time Frame: week 18 and 30 ]
    proportion of patients with viral load below detectable level of 50 copies/mL in plasma after ATI, week 18 and 30

  • Primary immune response against vaccine [ Time Frame: week 6 ]
    Change in frequency of at least 0.7log10 HIV-specific T-cell responses between baseline and week 6

  • CD8 T cell mediated viral suppression [ Time Frame: week 4 ]
    the in vivo vaccine-induced capacity of ex-vivo CD8 T cells to suppress HIV growth in autologous CD4 T cells

  • Viral reservoir [ Time Frame: week 4 and 6 ]
    effect on reservoir as measured by changes in the proviral DNA copy numbers per million cells and the intracellular viral RNA copy numbers per million cells during and after immunization

  • Viral Immune escape [ Time Frame: week 18 ]
    viral immune escape: change in % mutated epitopes from pre-cART to post-ATI

  • Transcriptomics [ Time Frame: week 6 and 18 ]
    host protein mRNA expression profiles in whole blood


Estimated Enrollment: 70
Actual Study Start Date: April 4, 2017
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: iHIVARNA-01
Biological: 1200μg mRNA (900 μg HIV mRNA+300 μg TriMix mRNA) 3 vaccinations, two weeks interval
Biological: iHIVARNA-01
Therapeutic vaccination, followed by treatment interruption
Other Names:
  • HIVACAT
  • TriMix
Biological: TriMix
Therapeutic vaccination, followed by treatment interruption
Active Comparator: TriMix
Biological: TriMix_300 μg TriMix mRNA 3 vaccinations, two weeks interval
Biological: TriMix
Therapeutic vaccination, followed by treatment interruption
Placebo Comparator: Placebo
Water for injection 3 vaccinations, two weeks interval
Biological: Placebo
Therapeutic vaccination, followed by treatment interruption

Detailed Description:

Objective: To evaluate the safety and immunogenicity of iHIVARNA-01 as a new therapeutic vaccine in HIV infected patients.

Study design and duration: Phase IIa, multicentre double-blind placebo controlled intervention study. Each patient will be followed for 30 weeks. The study duration will be 38 weeks from inclusion of the first patient.

Sites: Erasmus MC, Rotterdam The Netherlands (sponsor), Hospital Clínic de Barcelona and Institut de Recerca de la Sida - Caixa, Barcelona, Spain, Instituut voor Tropische Geneeskunde Antwerp, Belgium and Vrije Universiteit Brussel/UZ Brussel, Belgium

Study population: Chronically HIV-1- infected patients under stable cART with plasma viral load (pVL) ≤ 50 copies/ml and stable CD4+ T-cell counts ≥ 450/μl, aged 18 years or above.

Sample size: after recruitment and screening, 70 patients will be included and randomized to one of the study-arms.

Intervention: One group (n=40) receives the HIVACAT-TriMix (300 microgram TriMix + 900 microgram HIVACAT) vaccine intranodally on three occasions with a two-week interval. One control group (n=15) receives TriMix only (300 microgram TriMix) and one group (n=15) receives saline intranodally on three occasions with a two-week interval. Two weeks after the last vaccination cART treatment will be interrupted. If plasma virus is detectable, cART will be re-initiated twelve weeks after treatment interruption. cART can always be re-initiated for medical reasons, as judged by the clinical investigator.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. ≥ 18 years of age;
  2. Voluntarily signed informed consent;
  3. Proven HIV-1 infection (with documented antibodies against HIV-1 and a detectable plasma HIV-1 RNA before initiation of therapy);
  4. On stable treatment with cART regimen (antiretroviral therapy consisting of at least three registered antiretroviral agents) for at least 3 years;
  5. Nadir CD4+ ≥ 350 cells/μl (up to 2 occasional determinations ≤ 350 cells/μl are allowed);
  6. Current CD4+ cell count ≥ 450 cells/μl;
  7. 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);
  8. If sexually active, willing to use a reliable method of reducing the risk of transmission to their sexual partners during treatment interruption (including PrEP).

    1. 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. -

Exclusion Criteria:

  1. Treatment with non-cART regimen prior to cART regimen;
  2. Previous failure to antiretroviral and/or mutations conferring genotypic resistance to antiretroviral therapy;
  3. Non-subtype B HIV infection;
  4. Active Hepatitis B virus and/or Hepatitis C virus co-infection;
  5. History of a CDC class C event (see appendix A);
  6. Pregnant female (screened with a positive pregnancy test), lactating or intending to become pregnant during the study;
  7. Active malignancy ≤ 30 days (extended period on the clinical assessment of the investigator) prior to screening;
  8. Active infection with fever (38°C or above) ≤ 10 days of screening and/or first vaccination;
  9. 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;
  10. 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;
  11. Usage of any investigational drug ≤ 90 days prior to study entry;
  12. 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02888756

Contacts
Contact: Rob A Gruters, PhD +31107044063 r.gruters@erasmusmc.nl
Contact: Felipe Garcia, MD, PhD +34932275586 FGARCIA@clinic.cat

Locations
Belgium
Institute for Tropical Medicine Recruiting
Antwerp, Belgium
Contact: Eric Florence, MD, PhD         
UZ Brussel Recruiting
Brussels, Belgium
Contact: Sabine Allard, MD, PhD         
Netherlands
Erasmus MC Recruiting
Rotterdam, Netherlands
Contact: Eric van Gorp, MD, PhD         
Contact: Wesely de Jong, MD         
Spain
Hospital Universitari Germans Trias i Pujol Recruiting
Badalona, Spain
Contact: Beatriz Mothe, MD, PhD         
Hospital Clinic Enrolling by invitation
Barcelona, Spain
Sponsors and Collaborators
Rob Gruters
Institut d'Investigacions Biomèdiques August Pi i Sunyer
IrsiCaixa
Institute of Tropical Medicine, Belgium
Vrije Universiteit Brussel
Synapse bv
Asphalion
eTheRNA immunotherapies
CR2O
Hospital Clinic of Barcelona
Germans Trias i Pujol Hospital
Universitair Ziekenhuis Brussel
Investigators
Principal Investigator: Rob A Gruters, PhD Erasmus Medical Center
  More Information

Additional Information:
Responsible Party: Rob Gruters, Workgroup leader, Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT02888756     History of Changes
Other Study ID Numbers: iHIVARNA phase II
2016-002724-83 ( EudraCT Number )
Study First Received: August 23, 2016
Last Updated: August 10, 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rob Gruters, Erasmus Medical Center:
Immunotherapy
mRNA
Lentivirus infection
Virus disease
Sexually transmitted disease
Immunodeficiency syndrome

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 25, 2017