E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV-infected patients with Progressive Multifocal Leukoencephalopathy |
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E.1.1.1 | Medical condition in easily understood language |
HIV-infected patients with Progressive Multifocal Leukoencephalopathy |
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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 | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036807 |
E.1.2 | Term | Progressive multifocal leukoencephalopathy |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective of this study is to assess CYT107 efficacy on JCV clearance from cerebrospinal fluid. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are:
o to assess the clinical safety of CYT107
o to assess the effect on patient survival
o to measure the effect on neurological and clinical status
o to assess the biological activity of CYT107:
- on the kinetics of JCV reduction in CSF
- on the main parameters of the immune reconstitution
- on the specific T-cell response against the JC virus
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥18 years.
2. HIV-1 infection.
3. Neurological findings compatible with the development of active PML, established by criteria defined in protocol
4. Patients have to be on effective cART after PML diagnosis, for at least 4 weeks.
5. HIV RNA load in blood <1000 copies/mL.
6. Karnofsky Performance Status, score ≥ 30%.
7. Patient with medical insurance or government support.
8. Ability of the patient (or a legal representative if decision making capacity is impaired) to understand and sign informed consent. |
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E.4 | Principal exclusion criteria |
1. Pregnancy or breast feeding.
2. Refusal or inability to practice contraception regardless of the gender of the patient.
3. MRI documented PML-IRIS.
4. Prior treatment with interleukin-7.
5. Hepatitis B surface antigen (HBsAg) positive.
6. ALT and/or AST > 5 x ULN.
7. Use of another investigational or interventional treatment within the last 3 months prior to study entry.
8. Any current malignancy except Kaposi Sarcoma that does not require chemotherapy.
9. Current opportunistic CNS infection.
10. Active tuberculosis.
11. Other current severe illness or other conditions (such as autoimmune disease, severe mental illness) that, in the opinion of the investigator, would make the subject unsuitable for enrollment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is defined as the clearance of the JCV from the CSF at M3. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint will be assessed at 3 months. |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are:
• Kinetics of the JC viral load changes
• “Survival” curves for time to JCV viral clearance in CSF
• MRI lesions changes
• Percentage change in neurological scores
• Change in Karnofsky Performance Status;
• MRS scores
• Proportion of patients with a MRS score < 3
• Changes in CD4+ and CD8+ T-cell subsets
• Changes of specific T-cell responses, proliferation indices, JCV-specific T-cell responses
• Survival rate |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoints of evaluation of secondary endpoints are as follows:
• Kinetics of the JCV viral load changes from D0 to M3
• Kinetics of the JCV viral load changes from D0 to M12
• “Survival” curves for time to JCV viral clearance in CSF
• Percentage change in neurological scores between baseline and M12
• Change in Karnofsky Performance Status between D0 and M12;
• MRS scores at M12
• Survival rate at M12 |
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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 | Yes |
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 | Yes |
E.8.1.4 | Double blind | No |
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 | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | Information not present in EudraCT |
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 |
European Union |
Switzerland |
United States |
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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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Last patient last visit date. |
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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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |