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

NCT05468073 | Recruiting Phase 2 DMC

• 1 other identifier: D20-P012
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer Disease

Keywords

Interleukin; Neuroinflammation; Regulatory T cells; Microglia; Synaptic density

Outcome Measures

Primary Outcomes (1)

• Change from baseline CDR score at 18 months

  The primary endpoint will be evaluated in all patients evaluable for efficacy, i.e. patients who received at least one cure of IL-2 and were evaluated for cognitive and functional status at baseline and 18 months. The response variable will be dichotomized as follows: Responder patient = 1 (end of study CDR score \<= baseline CDR score) Non-responder patient = 0 (end of study CDR score \> baseline CDR score)

  18 months

Secondary Outcomes (9)

• Rate of cognitive decline between placebo and treatment groups as assessed by changes in MMSE scores at baseline, 6, 12, and 18 months

  6, 12 and 18 months

• Rate of cognitive decline between placebo and treatment groups as assessed by changes in ADAS-Cog 13 items scores at baseline, 6, 12, and 18 months

  6, 12 and 18 months

• Rate of functional decline between placebo and treatment groups as assessed by changes in ADCS-ADL MCI scores at baseline, 6, 12, and 18 months

  6, 12 and 18 months

• Rate of functional decline between placebo and treatment groups as assessed by changes in CDR (sum of boxes) scores at baseline, 6, 12, and 18 months

  6, 12 and 18 months

• Change in neuroimmune reaction as assessed by [18F]-DPA-714 PET global cortical index and regional cortical binding at baseline and 18 months between placebo and treated groups

  18 months

Study Arms (2)

Treatment

EXPERIMENTAL

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

Drug: Proleukin

Placebo

PLACEBO COMPARATOR

Patient will receive sodium chloride solution (NaCl)

Drug: Placebo

Interventions

Proleukin DRUG

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

Also known as: Interleukin 2

Treatment

Placebo DRUG

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

Also known as: Sodium chloride solution

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Centre Hospitalier St Anne: lead
• For Drug Consulting: collaborator

Study Sites (1)

GHU Saint Anne

Paris, 75674, France

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease; Neuroinflammatory Diseases

Interventions

aldesleukin; Interleukin-2; Sodium Chloride

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Marie SARAZIN, Prof

  GHU Saint Anne

  PRINCIPAL INVESTIGATOR

• Guillaume DOROTHEE, PhD

  INSERM UMRS 938

  STUDY CHAIR

• Michel BOTTLAENDER, Dr

  Service Hospitalier Frédéric Joliot / CEA

  STUDY CHAIR

Central Study Contacts

Khaoussou SYLLA, Dr

CONTACT

01 45 65 76 78; k.sylla@ghu-paris.fr

Viviane AWASSI

CONTACT

01 45 65 84 86; v.awassi@ghu-paris.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2020
• First Posted: July 21, 2022
• Study Start: October 11, 2022
• Primary Completion: September 1, 2025
• Study Completion (Estimated): September 1, 2026
• Last Updated: June 12, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)