Use of Low Doses of Interleukin-2 in Autism Spectrum Disorders (ALaDIN)

Autism spectrum disorders (ASD) are neurodevelopmental disorders that affect around 1% of the population. Matenral immune activation (MIA) during pregnancy is a risk factor for ASD in children (Han 2021), mediated by maternal secretion of IL-17a, which disrupts neurodevelopment (Choi 2016). MIA causes a long-lasting disruption of the Tregs/Th17 balance in offspring (decrease in anti-inflammatory Tregs/increase in pro-inflammatory Th17s) via epigenetic mechanisms (Lim 2021; Ellul 2021). In a mouse model of MIA, adoptive transfer of Tregs was able to normalise autistic behaviour, highlighting the importance of Tregs in maintaining the autistic phenotype (Xu, 2021). In this same model, we have shown that IL-2fd (i) stimulates Tregs, (ii) corrects meningeal inflammation (iii) normalises synaptic connectivity and (iv) normalises autistic behaviour in the offspring (Ellul 2025). In humans, the use of low doses of interleukin-2 (IL2-fd) (ILT-101) leads to activation and selective expansion of Tregs and a reduction in Th17 (Klatzmann 2015), including in children (Rosenzwajg 2020). We hypothesise that the use of IL2-fd (ILT-101) in ASD patients born to mothers with a history of MIA could correct the Tregs deficiency and improve autistic symptoms.

Study Overview

• Status: Not yet recruiting
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Drug: ILT-101 ld-(IL2); Drug: NaCl (0,9%)

Detailed Description

"A - Information and Inclusion: Patient identification and the proposal to participate in the research protocol will take place in the various screening units of the Child and Adolescent Psychiatry Department at Robert Debré Hospital, conducted by a child psychiatrist.

Inclusion and consent form signing will take place at the CIC (Clinical Investigation Center of Robert Debré Hospital) during the initial visit.

B - Patient follow-up during the trial:

Initial visit - The initial visit will take place at the CIC of Robert Debré Hospital. Randomization will then be carried out under the responsibility of the Robert Debré URC.

Follow-up visits - Subsequent visits for treatment administration will take place at the CIC. During these visits, patients will be assessed for clinical efficacy (Day 85, Day 169, Day 275) as well as safety/tolerance (Day 0, Day 8, Day 85, Day 169). They will also undergo biological sampling (Treg and Th17) on Day 0, Day 8, Day 29, and Days 85, 169, and 275.

C - End of study at Day 275.

Product presentation and origin:

ILT-101 will be provided free of charge by ILTOO Pharma, and the placebo will be prepared and supplied by AGEPS; both will be packaged in a double-blind manner. The administration schedule will be the same for ILT-101 and the placebo up to Day 169.

On Day 1, Day 29, Day 85, and Day 169, administration of the investigational treatment will take place at the CIC. From Day 2 to Day 5, Day 30 to Day 33, Day 57 to Day 61, Day 84 to Day 89, Day 113 to Day 117, Day 141 to Day 145, and Day 170 to Day 173, injections of ILT-101/placebo will be administered at the patients' homes by nurses from the Hospital-at-Home Department (AP-HP home hospitalization service)."

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Pierre ELLUL, MD; Phone Number: 0033140034131; Email: pierre.ellul@aphp.fr

Study Locations

• France
  • Paris, France, 75019
    • Robert Debré Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 6 to 8 years
• Meeting DSM-5 criteria for autism spectrum disorder
• ASD severity classified as moderate or severe on the ADOS

• Mother with :

  (i) an autoimmune disease (as listed by the American Autoimmune Related Diseases Association: https://www.aarda.org/diseaselist/) that began during the first and second trimesters of pregnancy, or that was present prior to pregnancy and experienced a relapse (defined as a change in disease activity leading to a change/modification of treatment) during pregnancy; (ii) a maternal infection (viral or bacterial) during pregnancy, defined as a fever greater than 38.5°C for at least 48 hours and documented (medical consultation, biological sample, prescription of antipyretic and/or antibiotic). Infections by a pathogen with a well-documented direct cerebral effect (CMV) will be excluded.

• Consent of parental authority and social security affiliation
• One of whose parents lives in the HAD pediatric intervention area.

Exclusion Criteria:

• Recent change in ASD management (behavioral therapy within 6 weeks, introduction of psychotropic molecules within 2 weeks)
• Contraindication to IL2 use (hypersensitivity, cancer history, active infection, obesity, transplant history, vaccination with live attenuated vaccine within 4 weeks)
• Participation in another therapeutic trial within the last 3 months
• BMI >95th percentile or BMI <5th percentile
• Participants who have already received a genetic diagnosis of ASD of the 'syndromic' type by DNA chip chromosome analysis
• Participants with hyperchloremia or hypernatremia
• Participant with uncontrolled epilepsy.
• Participants who are related to a person involved in the study at the investigating centre, the clinical research organisation (CRO) or the sponsor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; Administration of Interlukin-2	Drug: ILT-101 ld-(IL2); ILT-101 (0.8 MUI/m²/day) subcutaneously. Daily administration for 5 consecutive days (D1 to D5) every 4 weeks for 6 months (i.e. 7 courses of 5 days each).
Placebo Comparator: Control; Administration of Placebo NaCl 0.9%	Drug: NaCl (0,9%); Placebo (NaCl 0,9%), subcutaneously. Same administration schedule as for ILT-101.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Tregs (in % of CD4+ cells and absolute value) between baseline and Day 8, compared with ILT-101 and placebo.	To evaluate the stimulation of the Tregs of 6 to 8-years-old children with ASD whose mothers had MIA during pregnancy, by low doses of interleukin-2 (ILT-101) on day 8 versus placebo.	At Day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Score of Vineland II Adaptive Behavior Composite- Total Score	To assess the effect at Day 85 and Day169 of low doses of interleukin-2 (ILT-101) versus placebo on the Vineland II global score and the persistent effect at Day 275.	at Day 0, Day 85, Day 169 and Day 275
Score of Brief Observation of Social	Effect at Day 85 and Day 169 of ILT-101 versus placebo on the patient's other clinical dimensions (social cognition, repetitive behaviour and stereotypies, hyperactivity) and the residual effect at Day 275;	at Day 0, Day 85, Day 169 and Day 275
Score of Social Responsiveness Scale - total score	Effect at Day 85 and Day 169 of ILT-101 versus placebo on the patient's other clinical dimensions (social cognition, repetitive behaviour and stereotypies, hyperactivity) and the residual effect at Day 275;	at Day 0, Day 85, Day 169 and Day 275
Score of Autism Diagnostic observation schedule-2	Effect at Day 85 and Day 169 of ILT-101 versus placebo on the patient's other clinical dimensions (social cognition, repetitive behaviour and stereotypies, hyperactivity) and the residual effect at Day 275;	at Day 0, Day 85, Day 169 and Day 275
Score of Repetitive behaviour and stereotypies: Aberrant Behavior Checklist	Effect at Day 85 and Day 169 of ILT-101 versus placebo on the patient's other clinical dimensions (social cognition, repetitive behaviour and stereotypies, hyperactivity) and the residual effect at Day 275;	at Day 0, Day 85, Day 169 and Day 275
Score of Global functional impact: Clinical Global Improvement	Effect at Day 85 and Day 169 of ILT-101 versus placebo on the patient's other clinical dimensions (social cognition, repetitive behaviour and stereotypies, hyperactivity) and the residual effect at Day 275;	at Day 0, Day 85, Day 169 and Day 275
Score of Global functional impact: Caregiver Strain Index	Effect at Day 85 and Day 169 of ILT-101 versus placebo on the patient's other clinical dimensions (social cognition, repetitive behaviour and stereotypies, hyperactivity) and the residual effect at Day 275;	at Day 0, Day 85, Day 169 and Day 275
Treg Th17 assays (in % of CD4+ and absolute value) and CD25	Measurement of Tregs, Th17 and CD25 at Day 0, Day 8, Day 29 then at , Day 8 and Day 169 and the residual effect at Day 275; as well as the correlation between the biological response and socio-communicative symptoms at Day 85 and Day 169 and the residual effect at Day 275	at Day 0, Day 8, Day 29, Day 85, Day 169 and Day 275
Score of Pediatric adverse event rating scale	Tolerance	at Day 0, Day 8, Day 29, Day 85, Day169 and Day 275

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Iltoo Pharma

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: May 7, 2026
• First Submitted That Met QC Criteria: May 13, 2026
• First Posted (Actual): May 15, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Pregnancy; Autism Spectrum Disorder; Interleukin-2; ASI
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder
• Other Study ID Numbers: APHP230867; 2025-522841-23-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No