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.
Screening will take place during the 6 weeks prior to randomisation. Eligible participants will be enrolled at week 0 and randomised to MVA HIV-B vaccine followed by vedolizumab, vedolizumab + placebo vaccine, or placebo vaccine + placebo infusions. Participants will be randomised at each centre through web-based randomisation after entering the eligibility criteria. There will be two strata: one for those who started treatment during primary infection, and one for those who started treatment during chronic infection. 69 eligible individuals from collaborating European Countries will be enrolled, aiming for approximately half who started cART in primary infection and half who started in chronic infection. Participants continue from the screening visit (up to 6 weeks before enrolment) to the last visit, a maximum of 60 weeks (around 14 months), although follow-up will continue through to the time when virus is fully suppressed. Treatment will be interrupted at week 18 and resumed when the viral load is confirmed to have rebounded to ≥100,000 copies/ml, or the CD4 falls to ≤350 cells/mm3, confirmed, or there is evidence of disease progression, or they have completed 24 weeks of treatment interruption.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
2
Vaccine and vedolizumab infusion (Entyvio): 0.5ml of MVA HIV-B (1 x 108 pfu/ml) will be administered intramuscularly in the deltoid muscle of the non-dominant upper arm at weeks 0 and 8. Participants will be observed after the injection. Vedolizumab (300mg) is administered as an intravenous infusion (255 ml) over 30 mins in the dominant arm at weeks 10,12,16,20,24,28 and 32. After infusion, the line should be flushed with 30ml of normal saline. Participants will be observed throughout and after the infusion.
Placebo Vaccine: The placebo for MVA HIV-B to be used is a solution composed of S08 buffer (as for the MVA vaccine) that will be intramuscularly in the deltoid muscle of the non-dominant upper arm at weeks 0 and 8. Participants will be observed after the injection. Vedolizumab infusion (Entyvio): Vedolizumab (300mg) is administered as an intravenous infusion (255 ml) over 30 mins in the dominant arm at weeks 10,12,16,20,24,28 and 32. After infusion, the line should be flushed with 30ml of normal saline. Participants will be observed throughout and after the infusion.
Service Immunologie clinique et maladies infectieuses, Hôpital Henri Mondor
Paris, Creteil, France
Hotel Dieu
Paris, France
Centre d'Immunothérapie et Vaccinologie, CHUV
Lausanne, Canton of Vaud, Switzerland
St Stephens Centre, Chelsea & Westminster Hospital
London, United Kingdom
Area under the HIV RNA curve
Area under the HIV RNA curve from treatment interruption (scheduled for 18 weeks after entering the trial)
Time frame: Time from treatment interruption (scheduled for 18 weeks after entering the trial) to 24 weeks post-treatment interruption
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.
Time frame: For participants commencing treatment interruption only, critical time points weeks 19 through to to week 42.
Virological outcome measures
Level of HIV total RNA
Time frame: From randomisation to study completion about 54 weeks
Virological outcome measures
Cell Associated (CA) HIV RNA Quantification
Time frame: From randomisation to study completion about 54 weeks
Virological outcome measures
First local maximum (peak) level of HIV total RNA during treatment interruption
Time frame: Time from treatment interruption, only in participants commencing treatment interruption, up to 24 weeks after ATI
Virological outcome measures
Rate of increase of HIV total RNA between the last measure below the lower detection and the first local maximum
Time frame: Time from treatment interruption, only in participants commencing treatment interruption, up to 24 weeks after ATI
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Placebo Vaccine: The placebo for MVA HIV-B to be used is a solution composed of S08 buffer (as for the MVA vaccine) that will be intramuscularly in the deltoid muscle of the non-dominant upper arm at weeks 0 and 8. Participants will be observed after the injection. Placebo infusion (Entyvio): 255ml Sodium Chloride (NaCl) 0.9% bag administered as an intravenous infusion over 30 mins in the dominant arm at weeks 10,12,16,20,24,28 and 32. Participants will be observed throughout and after the infusion.
Virological outcome measures
Setpoint (two stable measures following a transient increase of HIV RNA)
Time frame: Time from treatment interruption, only in participants commencing treatment interruption, up to 24 weeks after ATI