E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human Immunodeficiency Virus type 1 infection |
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E.1.1.1 | Medical condition in easily understood language |
Human Immunodeficiency Virus type 1 infection |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068341 |
E.1.2 | Term | HIV-1 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 primary objective is to compare the safety and tolerability of the THV01 therapeutic HIV-1 vaccination by treatment group and versus placebo from W0 to W24. |
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E.2.2 | Secondary objectives of the trial |
One secondary objective is to compare the safety and tolerability of the THV01 therapeutic HIV-1 vaccination by treatment group and versus placebo: - From W-7 or W-2 (baseline) to W0; - From W24 to W36 or early termination; - From W36 to W88 or early termination.
Another secondary objective of the study is to compare the cellular immune responses by treatment group and versus placebo: - From W-7 or W-2 (baseline) to W0; - From W0 to W24; - From W24 to W36 or early termination; - From W36 to W88 or early termination.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients infected with clade B HIV-1 with a confirmed clade B genotyping performed at screening on the Gag protein; 2. Patient taking HAART for more than 24 months and at a stable doses regimen for at least 4 weeks; 3. Patients must be taking a ritonavir boosted protease inhibitor treatment among darunavir+ritonavir or lopinavir+ritonavir; 4. Patients’ HIV plasma viral load must have remained ≤ 100,000 copies mL-1 at any monitoring time (apart measurement during primo-infection if recorded); 5. Patients with HIV plasma viral load persistently ≤ 50 copies mL-1 during the 18 months prior to screening; 6. Patients’ CD4+ T cells count ≥ 300 cells per mm3 at any time since diagnosis; 7. Patients with CD4+ T cells count ≥ 600 cells per mm3 at baseline; 8. Man or woman aged 18-55 years; |
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E.4 | Principal exclusion criteria |
1. HIV-2 infection; 2. Any HIV protease inhibitor resistance mutation as listed in the current version of the HIV drug resistance database (Stanford University); 3. No virological failure as defined by a viral load ≥ 500 copies mL-1 measured twice, 7-14 days apart, since initiation of treatment; 4. A maximum of 2 blips with viral load comprised between 50 and 500 copies mL-1 are authorized during the 18 months prior inclusion; 5. History of an AIDS-defining clinical illness; 6. Concomitant AIDS-related opportunistic disease; 7. History of allergic disease, anaphylaxis or reactions likely to be triggered or exacerbated by any component of the vaccine such as lactose; 8. Acute or chronic infectious disease other than AIDS (include but not limited to viral hepatitis such as hepatitis B and hepatitis C, active tuberculosis, active syphilis, HTLV-1, HTLV-2); 9. Acute, chronic or history of clinically relevant pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic or renal functional abnormality, encephalopathy, neuropathy or unstable CNS pathology, angina or cardiac arrhythmias, or any other clinically significant medical problems as determined by physical examination and/or laboratory screening tests and/or medical history; 10. In particular, severe hepatic impairment; 11. Serious dyslipidemia; 12. Severe disorders of blood coagulation; 13. Known or suspected allergy to egg phospholipids, soy proteins and/or peanut; 14. Acute, chronic or history of immunodeficiency or autoimmune disease other than HIV infection; 15. Unstable asthma (defined as sudden acute attacks occurring in less than three hours without an obvious trigger, hospitalisation for asthma in the last two years); food or wine induced asthma; 16. History of malignancy unless there has been surgical excision that is considered to have achieved cure; 17. Active malignancy that may require chemotherapy or radiation therapy; 18. Seizure disorder or any history of prior seizure; 19. Subjects planning to receive a prophylactic or therapeutic vaccination during the study except Influenza immunization; 20. Subjects having an infective exacerbation during the screening process as defined as a requirement of inhaled, oral, or intravenous antibiotics prior to the first study dose; 21. Serious illness requiring systemic treatment and/or hospitalization within 7 days prior to study entry; 22. Recent (<24 hours) febrile illness on the day of vaccination (temperature > 38°C). 23. Pregnant or breast-feeding female; 24. Any contraindication of an intramuscular injection; 25. Active drug or alcohol abuse or dependence; 26. Any condition which, in the opinion of the investigator, could compromise the subject's safety or adherence to the study protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Occurrence of at least one grade 3 or higher adverse event including signs/symptoms, lab toxicities and/or clinical events possibly, probably or definitely related to study treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
#1 Occurrence of at least one grade 3 or higher adverse event including signs/symptoms, lab toxicities and/or clinical events possibly, probably or definitely related to study treatment.
#2 Monitoring the cellular immune response by cytokines and integrins quantification (IL-2; TNF-a; IFN-g; MIP-1b; CD40L and CD103); by monitoring the polyclonal activation (CD38; HLA-DR; CD45RA; CDR7 staining) and by ELISPOTs in the treatment group versus placebo. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timing of endpoint #1: - from baseline to W0; - from W24 to W36; - from W36 to W88 or early termination.
Timing of endpoint #2: - from baseline to W0: at W-2 or W-7 (depending on baseline date); - from W0 to W24: at W0; W4; W9; W12 and W24; - from W24 to W36 or early termination: at W28 and W36; - from W36 to W88 or early termination: at W48; W64 and W88 or early termination.
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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 | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 end 2 months after the last visit of the last patient. |
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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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |