Status and phase
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About
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.
Full description
The randomization ratio is 1:1:1:1 for vaccine: vedolizumab: combination: placebo in one of 3 schedules.
The study contains a phase I component in order to evaluate the local and systemic reactogenicity following the first administration of products in the first 12 participants. The phase I will consist of a slow enrolment of the first 12 participants who will be randomised at a maximum rate of 1 per week for 4 weeks, then 2 per week for 4 weeks before increasing to 4 or more per week. The IDMC will review of cumulative adverse event data through to and including the first safety visit in the 12th participant and their recommendation will be sought with regard to expanding recruitment.
The phase II component will assess the effectiveness and safety of the three experimental strategies upon viral control following analytic treatment interruption (ATI). The phase II component is divided into two stages, an interim efficacy stage and a final efficacy stage. There will be a pause in enrolment after 88 participants have been enrolled. A planned interim review by the IDMC at the end of the first stage will provide an opportunity to modify the design of subsequent stages or the recruitment strategy.
Screening will take place during the 6 weeks prior to randomisation. Eligible participants will be enrolled at week 0 and randomised to vaccine, vedolizumab, the combination of vaccine and vedolizumab or matched placebos. Participants and study staff will be aware of the schedule the participant is randomised to, with a third allocated to injections, a third to infusions and a third to the combination of injections and infusions. Only staff authorised to prepare the products will know who is randomised to active product or placebo within each schedule in a ratio of 3:1 respectively.
The vaccine regimen will start at week 0 and the vedolizumab regimen at week 2, each with matched placebo.
Participants will continue on cART during the first 24 weeks covering the vaccination period and 5 of 6 vedolizumab/placebo infusions.
Treatment will then be interrupted and resumed when the viral load is confirmed to have rebounded to ≥10,000 copies/ml, or the CD4 falls to ≤350 cells/mm3, or there is evidence of disease progression, or they have completed 24 weeks of treatment interruption.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Inclusion Criteria
HIV-1-infected
Aged 18 - 65 years old on the day of screening
Weight >50kg
Willing and able to provide written informed consent
Nadir CD4 count > 300 cells/mm3
CD4 count at screening > 500 cells/mm3
Viral load <50 copies/ml at screening
Started cART after 2009 and on cART for at least one year prior to screening
Willing to interrupt cART for up to 24weeks and change cART regimen if required
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)
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
If women of childbearing potential*, willing to undergo urine pregnancy tests prior to administration of an injection or an infusion
Willing to avoid all other vaccines within 4 weeks of scheduled study injections
Willing and able to comply with visit schedule and provide blood samples
Being covered by medical insurance or in National Healthcare System
Exclusion criteria:
Pregnant or lactating
HIV-2 infection (either isolated or associated with HIV-1)
VL >200 copies/ml on 2 occasions in the 12 months prior to screening
Previous interruptions in cART
Previous virological failures defined by loss of virological suppression with the presence of resistant mutations
Haemoglobin (Hb <12g/dL for males, <11g/dL for females)
Concomitant or previous conditions that preclude injection of vaccines/infusion of monoclonal antibody and PML in the past
History of experimental vaccinations against HIV
Previous treatment with chemotherapy (except for chemotherapy injected into skin lesions for Kaposi's sarcoma)
Treatment with systemic corticoids or immuno-suppressive agents ongoing or in the previous 12 weeks before randomisation in the trial
Received natalizumab or rituximab ever in the past
Received a TNF blocker in the past 60 days
Administration of an inactivated vaccine within 30 days or a live vaccine within 60 days prior to randomisation
Presence of a skin condition or marking that precludes inspection of the injection/infusion site
History of cancer (except basal cellular skin carcinoma or Kaposi's sarcoma)
History of significant neurological disease, cardiovascular disease (angina, myocardial infarction, transient ischemic attack, stroke); participants with controlled blood pressure are eligible
Personal history of clinical autoimmune disease or reactive arthritis or family history of rheumatoid arthritis (parents or siblings)
Ongoing diseases including uncontrolled active severe infection, cardiac, pulmonary (excluding mild asthma), thyroid, renal or neurological (peripheral or central) diseases
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)
Presence of pathogenic bacteria or parasites in faeces at screening
Participating in another biomedical research study within 30 days of randomisation.
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
Liver disease including hepatitis B (surface antigen positive) or hepatitis C (antigen or PCR positive)
A clinically significant abnormality on ECG
Hypernatraemia or hyperchloraemia
History of severe local or general reaction to vaccination defined as
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
Primary purpose
Allocation
Interventional model
Masking
1 participants in 4 patient groups, including a placebo group
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Data sourced from clinicaltrials.gov
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