A randomized, placebo controlled, multicenter phase IIb study of human recombinant Interleukin-7 (CYT107) in HIV-related Progressive Multifocal Leukoencephalopathy

• Register: EUCTR
• Last refreshed on: 10 March 2014
• Main ID: EUCTR2012-000725-41-GB
• Date of registration: 04/09/2012
• Prospective Registration: Yes
• Primary sponsor: Cytheris S.A.
• Public title: A randomized, placebo controlled, multicenter phase IIb study of human recombinant Interleukin-7 (CYT107) in HIV-related Progressive Multifocal Leukoencephalopathy
• Scientific title: A randomized, placebo controlled, multicenter phase IIb study of human recombinant Interleukin-7 (CYT107) in HIV-related Progressive Multifocal Leukoencephalopathy. - INVICTUS
• Date of first enrolment: 22/01/2013
• Target sample size: 57
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000725-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: yes Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

European Union, Italy, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: Cytheris Information
• Affiliation: Cytheris S.A.

• Name: Cytheris Information
• Affiliation: Cytheris S.A.

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 38
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 19

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

HIV-infected patients with Progressive Multifocal Leukoencephalopathy
MedDRA version: 15.0 Level: PT Classification code 10036807 Term: Progressive multifocal leukoencephalopathy System Organ Class: 10021881 - Infections and infestations

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Product Name: Recombinant human interleukin-7
Product Code: CYT107
Pharmaceutical Form: Solution for injection
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: CYT107
Other descriptive name: Recombinant human interleukin-7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 4-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: The primary endpoint will be assessed at 3 months.

Main Objective: The main objective of this study is to assess CYT107 efficacy on JCV clearance from cerebrospinal fluid.

Primary end point(s): The primary endpoint is defined as the clearance of the JCV from the CSF at M3.

Secondary Objective: 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

Secondary Outcome(s)

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

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

Secondary ID(s)

CLI-107-15

Source(s) of Monetary Support

Cytheris S.A.