An HIV Vaccine Trial in Individuals Who Started ART During Primary or Chronic Infection

• Status: Terminated
• Trial end date: 2019-07-11
• Target enrollment: 0
• Participant gender: All

Summary

EVHA T01 is an international, phase I/II, multicentre, multi-stage, double-blind study that will evaluate at least three experimental arms compared to placebo control in HIV-1 infected participants to see if one or more has a clinically relevant impact on the control of viral replication.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ANRS, Emerging Infectious Diseases; French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Collaborators: Centre Hospitalier Universitaire Vaudois; European Commission; European Georges Pompidou Hospital; FIT Biotech Ltd.; Fred Hutchinson Cancer Research Center; Henri Mondor University Hospital; Imperial College London; Institut d'Investigacions Biomèdiques August Pi i Sunyer; Istituto Nazionale Malattie Infettive Lazaro Spallanzani; Medical Research Council; Saint-Louis Hospital, Paris, France; Swiss Government; Universitätsklinikum Hamburg-Eppendorf; University College, London
• Treatments: Vaccines; Vedolizumab

Criteria

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 24weeks 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 an injection or an 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

• A woman will be considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.

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, cardiovascular disease (angina, myocardial infarction, transient ischemic attack, stroke); participants with controlled blood pressure are eligible

17. Personal history of clinical autoimmune disease or reactive arthritis or family history of rheumatoid arthritis (parents or siblings)

18. Ongoing diseases including uncontrolled active severe infection, 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 screening

21. Participating in another biomedical research study within 30 days of randomisation.

22. Known hypersensitivity to any component of the vaccine formulations used in this trial including aminoglycosides and 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. Hypernatraemia or hyperchloraemia

26. History of severe local or general reaction to vaccination defined as

1. local: extensive, indurated redness and swelling involving most of the arm, not resolving within 72 hours

2. general: fever >= 39.5oC within 48 hours; anaphylaxis; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours

27. Grade 2 or worse routine laboratory parameters (see Appendix 4 for definitions). Hyperbilirubinaemia to be considered an exclusion criterion only when confirmed to be conjugated bilirubinaemia