EHVA T02(European HIV Vaccine Alliance Therapeutic Trial02)/ANRS VRI07: A Phase II randomised, placebo-controlled trial of vedolizumab with or without therapeutic HIV MVA vaccine in individuals who started antiretrovirals during primary or chronic infectio

Phase 1

• Conditions: Human Immunodeficiency Virus (HIV) infection; MedDRA version: 20.1Level: PTClassification code 10020161Term: HIV infectionSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2019-002818-40-GB
• Lead Sponsor: Inserm-ANRS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-09-04
• Study Completion: 2023-07-12
• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

1. HIV-1-infected
2. Aged 18 – 65 years old on the day of screening
3. Weight >50kg
4. Willing and able to provide written informed consent
5. Nadir CD4 count > 300 cells/mm3
6. CD4 count at screening > 500 cells/mm3
7. Viral load <50 copies/ml at screening.
8. Started cART after 2009 and on cART for at least one year prior to screening
9. Willing to interrupt cART for up to 24 weeks and change cART regimen if required
10. 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 PrEP for their sexual partners)
11. If heterosexually active and able to have children, willing to use a highly effective method of contraception with partner (combined oral contraceptive pill; injectable or implanted contraceptive; IUD/IUS; physiological or anatomical sterility (in self or partner) from 2 weeks before enrolment until 18 weeks after the last injection/infusion
12. If women of childbearing potential, willing to undergo urine pregnancy tests prior to administration of any injection or infusion
13. Willing to avoid all other vaccines within 4 weeks of scheduled study injections
14. Willing and able to comply with visit schedule and provide blood samples
15. Being covered by medical insurance or in National Healthcare System
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 69
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1. Pregnant or lactating
2. HIV-2 infection (either isolated or associated with HIV-1)
3. VL >200 copies/ml on 2 occasions in the 12 months prior to screening
4. Previous interruptions in cART
5. Previous virological failures defined by loss of virological suppression with the presence of resistant mutations
6. Haemoglobin (Hb <12g/dL for males, <11g/dL for females)
7. Concomitant or previous conditions that preclude injection of vaccines/infusion of monoclonal antibody and PML in the past
8. History of experimental vaccinations against HIV
9. Previous treatment with chemotherapy (except for chemotherapy injected into skin lesions for Kaposi’s sarcoma)
10. Treatment with systemic corticoids or immuno-suppressive agents ongoing or in the previous 12 weeks before randomisation in the trial
11. Received natalizumab or rituximab ever in the past
12. Received a TNF blocker in the past 60 days
13. Administration of an inactivated vaccine within 30 days or a live vaccine within 60 days prior to randomisation
14. Presence of a skin condition or marking that precludes inspection of the injection/infusion site
15. History of cancer (except basal cellular skin carcinoma or Kaposi’s sarcoma)
16. History of significant neurological disease or cardiovascular disease (angina, myocardial infarction, transient ischemic attack, stroke); participants with controlled blood pressure are eligible
17. History of clinical autoimmune disease
18. Ongoing diseases including uncontrolled active severe infectiona, cardiac, pulmonary (excluding mild asthma), thyroid, renal or neurological (peripheral or central) diseases
19. Active or latent tuberculosis (unless prophylaxis in past as per local practice) - (participant must be screened for tuberculosis before starting infusions, according to routine practice)
20. Presence of pathogenic bacteria or parasites in faeces at screeninga
21. Participating in another biomedical research study within 30 days of randomisation
22. Known hypersensitivity to any component of the vaccine formulation used in this trial including eggs or have severe or multiple allergies to drugs or pharmaceutical agents, or any hypersensitivity to the active substance or to any of the excipients of vedolizumab.
23. Liver disease including hepatitis B (surface antigen positive) or hepatitis C (antigen or PCR positive)
24. A clinically significant abnormality on ECG
25. Hypernatraemiab or hyperchloraemiac
26. History of severe local or general reaction to vaccination defined as
- a.local: extensive, indurated redness and swelling involving most of the arm, not resolving within 72 hours
- b.general: fever >= 39.5°C within 48 hours; anaphylaxis; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours
27. Grade 2 or worse routine laboratory parameters.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The main objective of the study will be to assess the impact of vedolizumab and vaccination with MVA upon viral control following analytic treatment interruption (ATI). ;Secondary Objective: We plan to undertake a comprehensive analysis of the relationships between a range of biomarkers (including immune responses) and virological control, independent of vedolizumab/vaccination.;Primary end point(s): The primary outcome is the area under the HIV RNA curve from treatment interruption (scheduled to start at week 18 after entering the trial). HIV RNA is determined by the local laboratory using a standard assay. <br>;Timepoint(s) of evaluation of this end point: The time points for the primary outcome are all weekly visits from week 19 (visit 11) through to week 42 (visit 34).