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 vaccination (with DNA, MVA and/or vedolizumab) 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 vaccination/mAb. |
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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 |
In France, participants will be invited to take part in the following substudies: - rectal biopsy, - leukapheresis. |
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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. Written informed consent 5. Nadir CD4 count > 300 cells/mm3 6. CD4 count at screening > 600 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 child-bearing 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 |
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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, cardiovascular disease (angina, myocardial infarction, transient ischemic attack, stroke); participants with controlled blood pressure are eligible. 17. History of clinical autoimmune disease or reactive arthritis 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 - a.local: extensive, indurated redness and swelling involving most of the arm, not resolving within 72 hours - b. 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: Time from treatment interruption (scheduled for 24 weeks after enrolment) to the earliest time of reaching: - Confirmation of HIV RNA ≥ 10,000 copies/ml on a separate sample - Resuming antiretroviral therapy for any reason over a period of 24 weeks.
Safety: - A clinical decision to discontinue the regimen for an adverse event that is considered related to product. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The timepoints for the primary virological outcome measure are every week from week 25 through to week 48. Adverse events will be assessed at all weeks (except weeks -6, 12+1day, 25, 27, 29, 30, 33 and 35). |
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E.5.2 | Secondary end point(s) |
Secondary virological efficacy outcome measures: - Level of HIV total DNA - Cell Associated (CA) HIV RNA Quantification Secondary safety outcome measures: - Grade 3 and worse solicited clinical and laboratory adverse events - Any adverse event leading to interruption in the vaccine or vedolizumab schedule - Any event that results in resuming treatment during the ATI - Serious Adverse Events - Other clinical and laboratory adverse events - Time to VL suppression after restarting ART Secondary Immunological Outcomes: - Response rate, magnitude and polyfunctionality of vaccine induced CD4 and CD8 T-cell responses. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary virological outcomes will be assessed in all patients at week 24 and before cART is resumed and at Baseline if relevant. Depending on the results, secondary virological outcomes may be assessed at other timepoints. Adverse events will be assessed at all weeks (except weeks -6, 12+1day, 25, 27, 29, 30, 33 and 35). Secondary immunological outcomes will be assessed 2 weeks after the final immunisation at week 14. Depending on the results, secondary immunological outcomes may be assessed at other timepoints. |
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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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | 4 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | 7 |
E.8.9.1 | In the Member State concerned days | 15 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 15 |