E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human Immunodeficiency Virus (HIV) infection |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020161 |
E.1.2 | Term | HIV infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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). |
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E.2.2 | Secondary objectives of the trial |
We also plan to undertake a comprehensive analysis of the relationships between a range of biomarkers (including immune responses) and virological control, independent of vedolizumab/vaccination. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The sub-studies "gut biopsy" and "leukapheresis" incorporated in the main protocol, will be conducted in France and intend to study the effects of the treatment received in different compartments of the immune system. - A gut biopsy (rectal or sigmoid colon) will be collected from a subset of consenting participants between screening and three weeks before week 0 (and between weeks 16 and 17 at least 1 week before ATI). The biopsy will be collected using a proctoscope or sigmoidoscope. - Leukapheresis will be collected from a subset of consenting participants between screening and three weeks before week 0 (and between weeks 16 and 17 at least 1 week before ATI).
A separate protocol details the social science study; this is entitled: Expectation, Motivation and Experience of HIV-patients regarding participation to a European randomized phase II, placebo-controlled trial of vedolizumab with or without therapeutic HIV MVA vaccine (EHVA T02/ANRS VRI07) with interruption of ART (AMEP-EHVA T02). The main objective is to document the participant's expectations regarding this clinical trial and their motivations for participating in it, and to watch how these aspects change over time.
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E.3 | Principal 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 |
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome is the area under the HIV RNA curve from treatment interruption (scheduled at week 18 after entering the trial). HIV RNA is determined by the local laboratory using a standard assay.
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E.5.1.1 | 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). |
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E.5.2 | Secondary end point(s) |
Secondary virological outcomes: - 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 - Level of HIV total RNA - First local maximum (peak) level of HIV total RNA during treatment interruption - Rate of increase of HIV total RNA between the last measure below the lower detection limit (LDL) and the first local maximum - Setpoint
Secondary safety outcomes: - Grade 3 and worse solicited clinical and laboratory adverse events - Any adverse event leading to interruption in the vaccine/placebo or vedolizumab/placebo schedule - Any event that results in resuming treatment during the ATI - Serious Adverse Events - Other clinical and laboratory adverse events - Change in absolute CD4 - Time to VL suppression after restarting ART |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The time points for the secondary virological outcomes are all weekly visits from week 19 (visit 11) through to week 42 (visit 34).
Secondary safety outcomes are assessed at all visits except at week -6 (visit 1). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Germany |
Italy |
Spain |
Switzerland |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The trial will be closed when all participants have made their final follow-up visit and assessments completed, the data entered into the database and checked and the safety database locked. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |