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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

14 Nov 2024 → ongoing

Decision date (initial)

2024-11-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Fondation Plan Alzheimer and Fondation pour la Recherche Médicale

External identifiers

EU CT number

2024-516565-36-00

EudraCT number

2020-001495-14

ClinicalTrials.gov

NCT05468073

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

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

Secondary objectives 6

1. 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
2. regional and longitudinal variations in brain neuroinflammation measured by [18F]-DPA-714 PET imaging at baseline, at V19bis and 18 months after treatment induction,
3. peripheral frequency of Tregs and other immune effectors, as a biomarker of target engagement,
4. progression of hippocampal and regional cortical atrophy measured by MRI,
5. progression of synaptic density assessed by MRI NODDI sequences,
6. the clinical and biological safety and tolerability of IL-2 treatment

Conditions and MedDRA coding

Alzheimer Disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Patients aged > 18
2. 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.
3. Brain MRI congruent with the diagnosis, left to the appreciation of the investigator
4. CDR (Clinical Dementia Rating Scale) = 0.5 or 1
5. 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.
6. 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.
7. Have adequate vision and hearing for neuropsychological testing in the opinion of the investigator.
8. Have given written informed consent approved by the ethical review board (ERB) governing the site
9. The patient has to have a French social security number and be fluent and literate in French.

Exclusion criteria 22

1. Subject with a psychiatric evolutionary and/or badly checked
2. 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.
3. Epileptic subjects
4. Subject under guardianship or curatorship
5. Subject presenting contraindications to the MRI
6. Known or supposed history (< or = 5 years) of severe alcoholism or misuse of drugs
7. Vascular, inflammatory or expansive, visible lesion in the MRI, which can interfere on the criteria of diagnosis.
8. No health insurance
9. 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
10. History within the past 5 years of a primary or recurrent malignant disease (with the exception of fully excised non-melanoma skin cancers).
11. Diagnosis or history of other possible etiology of dementia, including but not limited to other neurodegenerative disorders (FTD, LBD, VaD, HD, PD, PSP-CBD)
12. Renal dysfunction at inclusion, clearance <30 mL/min
13. Chronic hepatic diseases as indicated by liver function tests abnormalities
14. Abnormal thyroid function
15. Therapeutic trial within 1 year preceding the first study period, or participation in a trial with active or passive immunization against amyloid
16. Clinically significant evidence of Active viral infection (CMV, EBV, HCV, HBV, TPHA-VDRL, HIV)
17. Current- or medical history of severe cardiopathy
18. Severe dysfunction in a vital organ
19. Patients with White Blood Count (WBC) < 4.000/mm3; platelets < 100.000/mm3; hematocrit (HCT) < 30%
20. Patients with serum bilirubin and creatinine outside normal range
21. Patients with organ allografts
22. Patients who are likely to require corticosteroids

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 10/12/2026

Secondary endpoints 1

1. 10/06/2027

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Sponsor organisation

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Address

1 Rue Cabanis

City

Paris

Postcode

75014

Country

France

Scientific contact point

Organisation

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Contact name

Pr Marie SARAZIN

Public contact point

Organisation

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Contact name

Pr Marie SARAZIN

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications