Therapeutic Evaluation of Low-dose IL-2-based Immunomodulatory Approach in Patients With Early AD

NCT ID: NCT05468073

Last Updated: 2024-06-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-11
• Study Completion Date: 2026-09-01

Brief Summary

Study aims at evaluating the therapeutic efficacy and safety of low-dose IL-2 immunomodulatory treatment in patients with early AD, in a phase II, randomized, double blind, placebo-controlled phase II clinical trial. Patients with AD at early stage will be recruited and randomized (2:1) in each treatment group.

The primary endpoint is the rate of decline assessed through CDR change at 18 months between the placebo group and the treated patients.

Detailed Description

This study aims to investigate the immunomodulatory therapeutic potential and safety of low-dose (ld) IL-2 in a randomized, double blind, and placebo-controlled phase II clinical trial.

Conservative diagnosis criteria based on clinical and CSF biomarkers have been established to avoid risks of misdiagnosis.

The treatment consist of 21 cures of subcutaneous injections of either placebo or low-dose (1MIU/day) IL-2 (PROLEUKIN ®). Patients will receive 5 consecutive injections during the induction phase which will be followed by a week break. During the maintenance phase a total of 16 injections will be administered weekly. Total duration of treatment for each patient is anticipated to be 18 weeks. Patients will be followed-up for 18 months after the first injection.

At inclusion, in addition to the clinical evaluation, a hybrid PET/MRI (using [18F]-DPA-714) scan will be performed. After randomized patients successfully complete the treatment phases, they will be followed-up through 3 clinical and 1 neuroimaging visits to assess cogitive and functional decline. Clinical visits are scheduled at 6, 12, and 18 months after treatment induction. Another hybrid PET/MRI (using [18F]-DPA-714) scan will be performed at 19 months following induction.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Treatment

Patient will be treated with low dose of Interleukin 2 (PROLEUKIN ®)

Group Type: EXPERIMENTAL

Proleukin

Intervention Type: DRUG

Sub-cutaneous injections of Interleukin-2 (PROLEUKIN ®) Induction phase: 5 consecutive days. A week break. Maintenance phase: once a week during 16 weeks

Placebo

Patient will receive sodium chloride solution (NaCl)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Sub-cutaneous injections of placebo (NaCl) Induction phase: 5 consecutive days. A week break. Maintenance phase: once a week during 16 weeks.

Interventions

Proleukin

Sub-cutaneous injections of Interleukin-2 (PROLEUKIN ®) Induction phase: 5 consecutive days. A week break. Maintenance phase: once a week during 16 weeks

Intervention Type: DRUG

Placebo

Sub-cutaneous injections of placebo (NaCl) Induction phase: 5 consecutive days. A week break. Maintenance phase: once a week during 16 weeks.

Intervention Type: DRUG

Other Intervention Names

Interleukin 2; Sodium chloride solution

Eligibility Criteria

Inclusion Criteria

• Patients aged > 18
• Age of disease onset < 70 years
• Clinical and biological diagnosis of AD based on

• Progressive amnestic syndrome associated or not with other cognitive impairments
• Biological criteria: CSF biomarkers suggestive of AD.
• Brain MRI congruent with the diagnosis, left to the appreciation of the investigator
• CDR (Clinical Dementia Rating Scale) = 0.5 or 1
• If patients have an antidepressant or acetylcholinesterase inhibitors treatment, patients must be treated with stable doses of treatment for at least 1 month before inclusion.
• Have a caregiver who provides a separate written informed consent to participate. If a caregiver/study informant cannot continue, one replacement is allowed.
• Have adequate vision and hearing for neuropsychological testing in the opinion of the investigator.
• Have given written informed consent approved by the ethical review board (ERB) governing the site.
• The patient has to have a French social security number and be fluent and literate in French.

Exclusion Criteria

• Subject with a psychiatric evolutionary and/or badly checked.
• Subject with a grave, severe or unstable pathology (left to the judgement of the investigator) the nature of which can interfere with the variables of evaluation.
• Epileptic subjects
• Subject under guardianship or curatorship
• Subject presenting contraindications to the MRI
• Known or supposed history (< or = 5 years) of severe alcoholism or misuse of drugs
• Vascular, inflammatory or expansive, visible lesion in the MRI, which can interfere on the criteria of diagnosis.
• No health insurance
• Women of childbearing potential: a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
• History of auto-immune disease
• History within the past 10 years of a primary or recurrent malignant disease
• Diagnosis or history of other possible etiology of dementia, including but not limited to other neurodegenerative disorders (FTD, LBD, VaD, HD, PD, PSP-CBD).
• Renal dysfunction at inclusion, clearance <30 mL/min
• Chronic hepatic diseases as indicated by liver function tests abnormalities
• Abnormal thyroid function
• Therapeutic trial within 1 year preceding the first study period, or participation in a trial with active or passive immunization against amyloid if patient was assigned to the active treatment arm.
• Clinically significant evidence of Active viral infection (CMV, EBV, HCV, HBV, TPHA-VDRL, HIV)
• Current or medical history of severe cardiopathy,
• - Severe dysfunction in a vital organ
• Patients with White Blood Count (WBC) < 4.000/mm3; platelets < 100.000/mm3; hematocrit (HCT) < 30%.
• Patients with serum bilirubin and creatinine outside normal range.
• Patients with organ allografts.
• Patients who are likely to require corticosteroids

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

For Drug Consulting

OTHER

Sponsor Role: collaborator

Centre Hospitalier St Anne

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marie SARAZIN, Prof

Role: PRINCIPAL_INVESTIGATOR

GHU Saint Anne

Guillaume DOROTHEE, PhD

Role: STUDY_CHAIR

INSERM UMRS 938

Michel BOTTLAENDER, Dr

Role: STUDY_CHAIR

Service Hospitalier Frédéric Joliot / CEA

Locations

GHU Saint Anne

Paris, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Khaoussou SYLLA, Dr

Role: CONTACT

k.sylla@ghu-paris.fr

01 45 65 76 78

Viviane AWASSI

Role: CONTACT

v.awassi@ghu-paris.fr

01 45 65 84 86

Facility Contacts

Viviane AWASSI

Role: primary

v.awassi@ghu-paris.fr

Nadine BEN MESSAOUD

Role: backup

nadine.ben_messaoud@ghu-paris.fr

Other Identifiers

D20-P012

Identifier Type: -

Identifier Source: org_study_id