ALDESLEUKIN for Alzheimer disease

Inclusion criteria

• {"criterion_text":"- Patients aged > 18\n- Clinical and biological diagnosis of AD based on o\tProgressive amnestic syndrome associated or not with other cognitive impairments o\tBiological criteria: CSF biomarkers suggestive of AD.\n- Brain MRI congruent with the diagnosis, left to the appreciation of the investigator\n- CDR (Clinical Dementia Rating Scale) = 0.5 or 1\n- 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.\n- 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.\n- Have adequate vision and hearing for neuropsychological testing in the opinion of the investigator.\n- Have given written informed consent approved by the ethical review board (ERB) governing the site\n- The patient has to have a French social security number and be fluent and literate in French."}

Exclusion criteria

• {"criterion_text":"- Subject with a psychiatric evolutionary and/or badly checked\n- History within the past 5 years of a primary or recurrent malignant disease (with the exception of fully excised non-melanoma skin cancers).\n- Diagnosis or history of other possible etiology of dementia, including but not limited to other neurodegenerative disorders (FTD, LBD, VaD, HD, PD, PSP-CBD)\n- Renal dysfunction at inclusion, clearance <30 mL/min\n- Chronic hepatic diseases as indicated by liver function tests abnormalities\n- Abnormal thyroid function\n- Therapeutic trial within 1 year preceding the first study period, or participation in a trial with active or passive immunization against amyloid\n- Clinically significant evidence of Active viral infection (CMV, EBV, HCV, HBV, TPHA-VDRL, HIV)\n- Current- or medical history of severe cardiopathy\n- Severe dysfunction in a vital organ\n- Patients with White Blood Count (WBC) < 4.000/mm3; platelets < 100.000/mm3; hematocrit (HCT) < 30%\n- 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.\n- Patients with serum bilirubin and creatinine outside normal range\n- Patients with organ allografts\n- Patients who are likely to require corticosteroids\n- Epileptic subjects\n- Subject under guardianship or curatorship\n- Subject presenting contraindications to the MRI\n- Known or supposed history (< or = 5 years) of severe alcoholism or misuse of drugs\n- Vascular, inflammatory or expansive, visible lesion in the MRI, which can interfere on the criteria of diagnosis.\n- No health insurance\n- 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"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is the rate of decline assessed through CDR change at 18 months between the placebo group and the treated patients.","definition_or_measurement_approach":"Rate of decline assessed through change in Clinical Dementia Rating (CDR) at 18 months between placebo and treated patients."}

Secondary endpoints

• {"endpoint_text":"- To investigate the impact of low-dose IL-2 treatment on - complementary cognitive and functional parameters assessed at the end of treatment period (V19), at 6, 12 and 18 months after starting the induction phase, - regional and longitudinal variations in brain neuroinflammation measured by [18F]-DPA-714 PET imaging at baseline, at V19bis and 18 months after treatment induction, - peripheral frequency of Tregs and other immune effectors, as a biomarker of target engagement, - progression of hippocampal and regional cortical atrophy measured by MRI, - progression of synaptic density assessed by MRI NODDI sequences, and - the clinical and biological safety and tolerability of IL-2 treatment","definition_or_measurement_approach":"Multiple measures including cognitive and functional parameters at specified visits (V19 and at 6, 12, 18 months), [18F]-DPA-714 PET imaging for neuroinflammation (baseline, V19bis, 18 months), peripheral Treg frequency as biomarker, MRI measures of hippocampal/regional cortical atrophy, MRI NODDI for synaptic density, and clinical/biological safety assessments."}
• {"endpoint_text":"- regional and longitudinal variations in brain neuroinflammation measured by [18F]-DPA-714 PET imaging at baseline, at V19bis and 18 months after treatment induction,","definition_or_measurement_approach":"[18F]-DPA-714 PET imaging assessed at baseline, immediately after treatment (V19bis) and 18 months after induction to measure regional and longitudinal neuroinflammation changes."}
• {"endpoint_text":"- peripheral frequency of Tregs and other immune effectors, as a biomarker of target engagement,","definition_or_measurement_approach":"Peripheral blood immunophenotyping to quantify Treg frequency and other immune effector populations as biomarkers of target engagement."}
• {"endpoint_text":"- progression of hippocampal and regional cortical atrophy measured by MRI,","definition_or_measurement_approach":"Structural MRI assessments of hippocampal and regional cortical atrophy progression over time."}
• {"endpoint_text":"- progression of synaptic density assessed by MRI NODDI sequences,","definition_or_measurement_approach":"MRI NODDI sequence-derived measures to assess changes in synaptic density."}
• {"endpoint_text":"- the clinical and biological safety and tolerability of IL-2 treatment","definition_or_measurement_approach":"Clinical and laboratory safety assessments and adverse event monitoring throughout treatment and follow-up."}

France

Earliest CTIS Part Ii Submission Date

14-10-2024

Latest Decision Or Authorization Date

13-06-2025

Processing Time Days

242

Number Of Sites

1

Number Of Participants

45

Primary sponsor

Full Name

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Fondation Plan Alzheimer and Fondation pour la Recherche Médicale","duties_or_roles":"Source of monetary support","organisation_type":""}