ML-004 in Adolescents and Adults With Autism Spectrum Disorders (ASD)

Study Overview
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Brief Summary
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ML-004-002 is a multi-center, randomized, double-blind, placebo-controlled study that will enroll approximately 150 adolescent and adult subjects with ASD

Detailed Description
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ML-004-002 is a Phase 2, multi-center, randomized, double-blind, placebo- controlled study that will enroll approximately 150 adolescent and adult subjects with ASD. The primary objective of the study will be to evaluate the efficacy of ML-004 compared with placebo for the treatment of care/study partner-reported social communication deficits in patients with ASD. Subjects will be randomized to study treatment in a 1:1 ratio of ML-004: placebo. Treatment will begin with 2 weeks of once daily dosing of ML-004 or placebo followed by a 9-12 day dose-titration phase until the maximum allowable tolerated dose (based on subject weight) is reached. The maximum dose tolerated during dose titration will become the maintenance dose (MD) for that subject, and the subject will remain on this dose for 12 weeks, followed by a down titration. An independent DSMC will monitor trial progress and ensure that the safety of trial subjects is not compromised.

Official Title
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A Randomized, Double-blind, Parallel Group, Placebo-controlled Study to Investigate the Efficacy, Safety, and Tolerability of ML-004 in Adolescents and Adults With Autism Spectrum Disorders (ASD).

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Drug: ML-004 (IR)/(ER) tablet
* Drug: ML-004 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 12 to 45 at screening Has a designated care/study partner who can reliably report on symptoms Has a diagnosis of Autism Spectrum Disorder (ASD) Full scale IQ (or equivalent) ≥70 score Psychoactive medications and adjunctive therapies are stable for 4 weeks prior to screening Must be able to swallow study medication Exclusion Criteria: Has Rett syndrome or Child Disintegrative Disorder Has participated in any other study and received any other investigational medication (other than COVID-19 vaccination) or device within 60 days prior to screening History of epilepsy without current adequate control, or any seizure in the 6 months preceding screening History of suicidal ideation or behavior in the past 12 months, or a positive response to C-SSRS questions 4 and/or 5 Systolic blood pressure ≥160 mmHg, or diastolic blood pressure ≥100, or a clinical history of uncontrolled or severe hypertension If female, is pregnant or lactating

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multi-center, randomized, double-blind, placebo-controlled study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ML-004 (IR)/(ER) tablet<br>ML-004 is a bilayer immediate-release (IR)/extended-release (ER, gastroretentive) oral tablet formulation. ML-004 is taken orally once daily and provided as a tablet in two dose strengths of 12 mg (3 mg IR/9 mg ER) and 24 mg tablet (6 mg IR/18 mg ER). Dose levels for this study are 12 mg (provided as one 12 mg tablet), 24 mg (one 24 mg tablet), 48 mg (two 24 mg tablets), and 72 mg (three 24 mg tablets). | Drug: ML-004 (IR)/(ER) tablet<br>* Participants will receive ML-004 once daily for up to 16 weeks.<br>|
| Placebo Comparator: ML-004 Placebo<br>Matched placebo oral tablets will consist of same excipients as the investigational drug but without any ML-004. Placebo taken orally once daily to match tablet number of ML-004 dose levels for 12 mg (1 tablet), 24 mg (1 tablet), 48 mg (2 tablets), and 72 mg (3 tablets). | Drug: ML-004 Placebo<br>* Participants will receive matching placebo once daily for up to 16 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Autism Behavior Inventory (ABI)-Social Communication Domain Score | Change from baseline in the ABI-Social Communication Domain Score will be reported. The ABI is a 62-item questionnaire for reporting the behaviors of subjects (ages: 3 years-adulthood) diagnosed with ASD. The tool is suitable for completion by parents or care/study partners of people with ASD. Each item assesses either quality (from not at all to without help) or frequency (never to very often) of a particular behavior. The Social Communication domain score is the sum of the scores in the social communication domain divided by the number of items in the domain. | Baseline up to Day 110 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Clinician Global Impression of Improvement (CGI-I) | The CGI-I score is a single-item instrument based on a 7-point scale routinely used in clinical trials to capture the Investigator's global impression of response. The Investigator or designee rates the improvement observed from 1 (very much improved) to 7 (very much worse). | Day 110 | 
| Change from Baseline in Autism Behavior Inventory-Clinician (ABI-C) Score | The ABI-Clinician (ABI-C) captures the clinician rating of behaviors of a person with ASD that occurred over the week prior to assessment. It contains 14 items reflecting the core and associated autism behavior domains: Social Communication, Restrictive Behaviors, Mood and Anxiety, Self Regulation, and Challenging Behavior. Each item is rated on a 7-point scale from 1 (none; no symptoms present) to 7 (very severe; persistent interference with function or adaptation). | Baseline up to Day 110 | 
| Change from Baseline in Aberrant Behavior Checklist 2-Irritability (ABC-I) Subscale Score | The ABC is a parent- or care/study partner-reported behavior rating assessment with five domains and 58 items, each rated on a 0 (not a problem) to 3 (the problem is severe in degree) scale. The irritability domain consists of 15 items. | Baseline up to Day 110 | 
| Change from baseline in the Clinician Global Impression of Severity (CGI-S) Score | The CGI-S is a global assessment of the clinician-rater's impression of the severity of the participant's illness. It is rated on a scale of 1 (normal, not at all ill) to 7 (among the most extremely ill). | Baseline up to Day 110 | 
| Change from baseline in the ABI Repetitive/Restrictive Behavior Domain Score | Each item on the ABI-Repetitive/Restrictive Behavior Domain is rated by frequency (0=never to 3=very often). The domain score is the sum of all domain items scores divided by the number of items in the domain. | Baseline up to Day 110 | 
| Change from baseline in the ABI Mood and Anxiety Domain Score | Each item on the ABI- Mood and Anxiety Domain is rated by frequency (0=never to 3=very often). The domain score is the sum of all domain items scores divided by the number of items in the domain. | Baseline up to Day 110 | 
| Change from baseline in the ABI Challenging Behavior Domain Score | Each item on the ABI- Challenging Behavior Domain is rated by frequency (0=never to 3=very often). The domain score is the sum of all domain items scores divided by the number of items in the domain. | Baseline up to Day 110 | 
| Change from baseline in the ABI Self-regulation Domain Score | Each item on the ABI- Self-regulation Domain is rated by frequency (0=never to 3=very often). The domain score is the sum of all domain items scores divided by the number of items in the domain. | Baseline up to Day 110 | 
| Change from baseline in the ABI-Short Form (ABI-S) Score | The ABI-S is a 24-item short version of the ABI, containing items from each of the five domains. The domain score for each domain is calculated as the sum of scores all domain items divided by the number of items in the domain. | Baseline up to Day 110 | 
| Change from baseline in the ABC-Social Withdrawal (ABC-SW) Subscale Score | The ABC-SW subscale consists of 16 items of the ABC-2 rated from 0 (not a problem) to 3 (the problem is severe in degree). | Baseline up to Day 110 | 
| Change from baseline in the Social Responsiveness Scale 2 (SRS-2) Score | The SRS-2 consists of 65 items across 5 subscales. Responses range from 1 (not true) to 4 (almost always true). | Baseline up to Day 110 | 
| Change from baseline in the Vineland-3 (Domain Level Version) Score: total of Communication, Socialization, and Maladaptive behavior domains | The Vineland-3 Domain Level Version contains 5 domains. Responses on each item are rated from 0 (never) to 2 (usually). | Baseline up to Day 110 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ASD, Autism, Autism Spectrum Disorder, social communication deficit