HIV-1-infection Clinical Trial
Official title:
EHVA T02 (European HIV Vaccine Alliance Therapeutic Trial 02)/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 Infection
Verified date | July 2023 |
Source | ANRS, Emerging Infectious Diseases |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
EHVA T02 is an international, phase II, double-blind study to evaluate two experimental arms each compared to placebo control in HIV-1 positive participants to see if either has a clinically relevant impact on viral replication.
Status | Completed |
Enrollment | 2 |
Est. completion date | July 12, 2023 |
Est. primary completion date | July 12, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | 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 an injection and 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 12 weeks prior to 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 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 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. 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. Hyperbilirubinaemia to be considered an exclusion criterion only when confirmed to be conjugated bilirubinaemia |
Country | Name | City | State |
---|---|---|---|
France | Hotel Dieu | Paris | |
France | Service Immunologie clinique et maladies infectieuses, Hôpital Henri Mondor | Paris | Creteil |
Switzerland | Centre d'Immunothérapie et Vaccinologie, CHUV | Lausanne | Vaud |
United Kingdom | St Stephens Centre, Chelsea & Westminster Hospital | London |
Lead Sponsor | Collaborator |
---|---|
ANRS, Emerging Infectious Diseases | Centre Hospitalier Universitaire Vaudois, Chelsea and Westminster Hospital, UK, Erasmus Medical Center, European AIDS Treatment Group (EATG), European Commission, European Georges Pompidou Hospital, EuroVacc Foundation, Henri Mondor University Hospital, Hospital Clinic of Barcelona, 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 Hospitals, University of Liverpool |
France, Switzerland, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Safety outcome measures: Grade 3 or worse solicited clinical and laboratory adverse events | Occurrence of grade 3 or worse solicited clinical and laboratory adverse events | From randomisation to study completion about 54 weeks | |
Other | Safety outcome measures: Any adverse event leading to interruption in the vaccine/placebo or vedolizumab/placebo | Occurrence of any adverse event leading to interruption in the vaccine/placebo or vedolizumab/placebo | From randomisation to study completion about 54 weeks | |
Other | Safety outcome measures: Any event that results in resuming treatment during the ATI | Occurrence of any event that results in resuming treatment during the ATI | Time form treatment interruption to resuming treatment, up to 24 weeks after ATI | |
Other | Safety outcome measures: Serious Adverse Events | Occurrence of Serious Adverse Events | From randomisation until 30 days after the last protocol visit | |
Other | Safety outcome measures: Other clinical and laboratory adverse events | Occurrence of other clinical and laboratory adverse events | From randomisation to study completion about 54 weeks | |
Other | Safety outcome measures: Change in absolute CD4 | Observation of change in absolute CD4 count | From randomisation to study completion about 54 weeks | |
Other | Safety outcome measures: Time to VL suppression after restarting cART | Time to VL suppression after restarting cART | From randomisation to VL suppression (= VL is undetectable (<50copies/ml)) after restarting cART until the participant returns to an undetectable viral load, about 54 weeks] | |
Other | Exploratory Immunological outcome measures: Characterization of vaccine induced CD4 and CD8 T-cell produced cytokine profile | Observation of vaccine induced CD4 and CD8 T-cell produced cytokines by flow cytometry | From randomisation to study completion about 54 weeks | |
Primary | Area under the HIV RNA curve | Area under the HIV RNA curve from treatment interruption (scheduled for 18 weeks after entering the trial) | Time from treatment interruption (scheduled for 18 weeks after entering the trial) to 24 weeks post-treatment interruption | |
Secondary | Virological outcome measures | Time from treatment interruption (scheduled for 18 weeks after entering the trial) to the earliest of reaching HIV RNA = 100 000 copies/ml (confirmed on a separate sample) or resuming antiretroviral therapy for any reason over a period of 24 weeks. | For participants commencing treatment interruption only, critical time points weeks 19 through to to week 42. | |
Secondary | Virological outcome measures | Level of HIV total RNA | From randomisation to study completion about 54 weeks | |
Secondary | Virological outcome measures | Cell Associated (CA) HIV RNA Quantification | From randomisation to study completion about 54 weeks | |
Secondary | Virological outcome measures | First local maximum (peak) level of HIV total RNA during treatment interruption | Time from treatment interruption, only in participants commencing treatment interruption, up to 24 weeks after ATI | |
Secondary | Virological outcome measures | Rate of increase of HIV total RNA between the last measure below the lower detection and the first local maximum | Time from treatment interruption, only in participants commencing treatment interruption, up to 24 weeks after ATI | |
Secondary | Virological outcome measures | Setpoint (two stable measures following a transient increase of HIV RNA) | Time from treatment interruption, only in participants commencing treatment interruption, up to 24 weeks after ATI |
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