ML-004 Open-Label Extension Study in Adults and Adolescents With Autism Spectrum Disorders (ASD)

Study Overview
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Brief Summary
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ML-004-003 is a multi-center, open-label extension study that will enroll approximately 120 adolescent and adult subjects with ASD that have completed study ML-004-002.

Detailed Description
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ML-004-003 is a Phase 2, multi-center, open-label extension study to assess the safety and tolerability in approximately 120 adolescent and adult subjects (age 12 years to 45 years) with ASD who completed the antecedent Phase 2, double-blind, placebo-controlled, study ML-004-002. The primary objective of the study will be to evaluate the safety of ML-004 in subjects with ASD. Subjects will enroll into the study within 3 months of completing antecedent study ML-004-002. Treatment will be once daily and begin with a 12 day dose-titration phase until the maximum allowable tolerated dose is reached. This dose will become the maintenance dose (MD) for that subject, and the subject will remain on this dose for 50 weeks, followed by a down titration.

Official Title
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An Open-label Extension Study to Investigate 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has completed Study ML-004-002 within the past 90 days Age 12 years to 45 years at screening Has a designated care/study partner who can reliably report on symptoms Has a diagnosis of Autism Spectrum Disorder (ASD) BMI ≥ 18 kg/m2 Psychoactive medications and adjunctive therapies stable for 4 weeks prior to screening Able to swallow study medication Exclusion Criteria: Has Rett syndrome or Child Disintegrative Disorder History of epilepsy without current adequate control, or any seizure in the 6 months preceding screening Has a positive response to C-SSRS questions 4 and/or 5, or is a significant risk for suicidal behavior Has 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
Intervention Model: Single Group Assignment
Interventional Model Description: Multi-center, open-label study
Masking: None (Open Label)


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 a total of 53 weeks. Dose Titration Phase to Maintenance Dose (up to 12 days) Maintenance Dose Phase (350 days [50 weeks]) Down-Titration Phase (up to 9 days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of occurrence of treatment-emergent adverse events (TEAEs). |  | Baseline up to Day 401 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of occurrence of Serious Adverse Events (SAEs) |  | Baseline up to Day 401 | 
| Frequency of occurrence of TEAEs leading to discontinuation. |  | Baseline up to Day 401 | 
| Frequency of occurrence of TEAEs arising from clinically important changes in other safety assessments. |  | Baseline up to Day 401 | 
| Frequency of occurrence of suicidal ideation and behavior as assessed by the Columbia-Suicide Severity Rating Scale. |  | Baseline up to Day 401 | 

 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