Overview

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.

Eligibility

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