Use of Low Doses of Interleukin-2 in Autism Spectrum Disorders

Overview

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.

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)."

Interventions

• 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).
• Drug NaCl (0,9%)
  Placebo (NaCl 0,9%), subcutaneously. Same administration schedule as for ILT-101.

Primary outcome measures

• Change in Tregs (in % of CD4+ cells and absolute value) between baseline and Day 8, compared with ILT-101 and placebo. [Time frame: At Day 8]

Secondary outcome measures (9)

• Score of Vineland II Adaptive Behavior Composite- Total Score [Time frame: at Day 0, Day 85, Day 169 and Day 275]
• Score of Brief Observation of Social [Time frame: at Day 0, Day 85, Day 169 and Day 275]
• Score of Social Responsiveness Scale - total score [Time frame: at Day 0, Day 85, Day 169 and Day 275]
• Score of Autism Diagnostic observation schedule-2 [Time frame: at Day 0, Day 85, Day 169 and Day 275]
• Score of Repetitive behaviour and stereotypies: Aberrant Behavior Checklist [Time frame: at Day 0, Day 85, Day 169 and Day 275]
• Score of Global functional impact: Clinical Global Improvement [Time frame: at Day 0, Day 85, Day 169 and Day 275]
• Score of Global functional impact: Caregiver Strain Index [Time frame: at Day 0, Day 85, Day 169 and Day 275]
• Treg Th17 assays (in % of CD4+ and absolute value) and CD25 [Time frame: at Day 0, Day 8, Day 29, Day 85, Day 169 and Day 275]
• Score of Pediatric adverse event rating scale [Time frame: at Day 0, Day 8, Day 29, Day 85, Day169 and Day 275]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

France · 1 center

• Robert Debré Hospital — Paris

Identifiers

NCT: NCT07589842 · APHP230867 · 2025-522841-23-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗