Therapeutic evaluation of low-dose IL-2-based immunomodulatory approach in patients with early Alzeihmer Disease

Phase 2

Not yet recruiting

Conditions: Alzheimer Disease

Registration Number: 2024-516565-36-00

Lead Sponsor: Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Brief Summary: 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.

Recruitment & Eligibility

Status: Authorised, recruitment pending

Sex: Not specified

Target Recruitment: 45

Inclusion Criteria

Patients aged > 18

Clinical and biological diagnosis of AD based on o Progressive amnestic syndrome associated or not with other cognitive impairments o 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.

The subject lives with (or has regular periods of contact with) a permanent caregiver who is ready to attend the inclusion and the clinical follow-up visits (V1, V20, V21, V22), is ready to attend or to be contacted for each treatment visit (V3 to V19), supervises the subject’s compliance with the procedures specified in the protocol, and reports on subject’s condition.

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

History within the past 5 years of a primary or recurrent malignant disease (with the exception of fully excised non-melanoma skin cancers).

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

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%

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.

Patients with serum bilirubin and creatinine outside normal range

Patients with organ allografts

Patients who are likely to require corticosteroids

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
10/12/2026		10/12/2026

Secondary Outcome Measures

Name	Time	Method
10/06/2027		10/06/2027

Trial Locations

Locations (1): Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience
🇫🇷
Paris, France
Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience
🇫🇷Paris, France
Marie SARAZIN
Site contact
0145656173
m.sarazin@ghu-paris.fr