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

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).

ML-004-002 is a multi-center, randomized, double-blind, parallel-group, placebo-controlled study that will enroll approximately 150 adolescent and adult subjects with ASD. The primary objective is to evaluate the efficacy of ML-004 compared with placebo in the improvement of social communication deficits in subjects with ASD.

Study Overview

• Status: Recruiting
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Drug: ML-004 (IR)/(ER) tablet; Drug: ML-004 Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alexis Levine; Phone Number: +1 650-839-4388; Email: alevine@maplightrx.com

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Brain and Mind Centre
      • Contact: Adam Gaustella, Prof; Phone Number: +61 2 9351 0539
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Recruiting
      • Children's Health Queensland Hospital and Health Service
      • Contact: Helen Heussler, MBBS; Phone Number: 617 3068 3815
    • South Brisbane, Queensland, Australia, 4101
      • Recruiting
      • Mater Research
      • Contact: Catherine Franklin, MBBS; Phone Number: 07 3163 2412
  • South Australia
    • Adelaide, South Australia, Australia, 5042
      • Recruiting
      • Flinders Medical Centre
      • Contact: Dylan Mordaunt, MBBS; Phone Number: 618 8240 4623
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Recruiting
      • The Royal Children's Hospital, Murdoch Children's Research Institute
      • Contact: David Amor, MBBS; Phone Number: 613 9936 6404
• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1Z9
      • Recruiting
      • OCT Research ULC (dba Okanagan Clinical Trials)
      • Contact: Euguene Okorie, MD; Phone Number: 250-862-8141
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Recruiting
      • Lawson Health Research Institute/ London Health Sciences Centre
      • Contact: Rob Nicolson, MD, FRCP (C); Phone Number: 519-685-8427
    • Toronto, Ontario, Canada, M4G 1R8
      • Recruiting
      • Holland Bloorview Kids Rehabilitation Hospital
      • Contact: Danielle Baribeau, MD; Phone Number: 416-753-6005
• United States
  • Alabama
    • Dothan, Alabama, United States, 36303
      • Recruiting
      • Harmonex Neuroscience Research
      • Contact: Nelson Handal-Thome, MD; Phone Number: 334-836-2000
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Recruiting
      • Southwest Autism Research & Resource Center, Clinical Research
      • Contact: Christopher Smith, PhD; Phone Number: 480-443-0050
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco
      • Contact: Tomoyo Hirota, DO; Phone Number: 415-476-7044
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Recruiting
      • Yale Child Study Center
      • Contact: Roger Jou, MD, PhD
      • Contact: Phone Number: 203-737-4378
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Recruiting
      • Children's National Health System - The Children's Research Institute (CRI)
      • Contact: Adelaide Robb, MD; Phone Number: 202-476-3042
  • Florida
    • Orlando, Florida, United States, 32803
      • Recruiting
      • APG Research, LLC
      • Contact: Morteza Nadjafi, MD; Phone Number: 407-423-7149
    • Tampa, Florida, United States, 33613
      • Recruiting
      • University of South Florida Psychiatry and Behavioral Neurosciences
      • Contact: Daniel Fallon, MD; Phone Number: 813-974-4657
  • Illinois
    • Naperville, Illinois, United States, 60563
      • Active, not recruiting
      • AMR-Baber Research Inc
  • Massachusetts
    • Lexington, Massachusetts, United States, 02421
      • Recruiting
      • Massachusetts General Hospital's Lurie Center for Autism
      • Contact: Christopher Keary, MD; Phone Number: 781-860-1729
  • Michigan
    • Bloomfield Hills, Michigan, United States, 48302
      • Recruiting
      • Neurobehavioral Medicine Group
      • Contact: Richard Jackson, MD; Phone Number: 248-290-5400
  • Missouri
    • Columbia, Missouri, United States, 65211
      • Recruiting
      • University of Missouri, Thompson Center for Autism & Neurodevelopmental Disorders
      • Contact: Benjamin Black, MD; Phone Number: 573-884-6052
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Recruiting
      • Hassman Research Institute
      • Contact: Steve Glass, MD; Phone Number: 350 856-753-7335
    • Neptune, New Jersey, United States, 07753
      • Recruiting
      • Jersey Shore University Medical Center
      • Contact: Stacy Doumas, MD; Phone Number: 732-776-4930
  • New York
    • Orangeburg, New York, United States, 10962
      • Recruiting
      • Nathan Kline Institute for Psychiatric Research
      • Contact: Russell Tobe, MD; Phone Number: 845-398-5525
    • Staten Island, New York, United States, 10314
      • Recruiting
      • Richmond Behavioral Associates
      • Contact: Mark DiBuono, MD; Phone Number: 1301 718-317-5522
    • White Plains, New York, United States, 10605
      • Recruiting
      • Center for Autism and the Developing Brain, New York State Psychiatric Institute
      • Contact: Jeremy Veenstra-VanderWeele, MD; Phone Number: 646-774-5251
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University Nisonger Center
      • Contact: Eugene Arnold, MD; Phone Number: 614-685-6701
  • Pennsylvania
    • Media, Pennsylvania, United States, 19063
      • Recruiting
      • Suburban Research Associates
      • Contact: Shivkumar Hatti, MD; Phone Number: 610-891-7200
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Contact: Amanda Bennett, MD; Phone Number: 267-366-8371
  • Texas
    • Houston, Texas, United States, 77090
      • Terminated
      • Red Oak Psychiatry Associates, PA
    • San Antonio, Texas, United States, 78249
      • Recruiting
      • Road Runner Research, Ltd.
      • Contact: Jerry Tomasovic, MD; Phone Number: 210-949-0505
  • Utah
    • Draper, Utah, United States, 84020
      • Recruiting
      • Cedar Clinical Research
      • Contact: Paul Thielking, MD; Phone Number: 801-704-9722
  • Washington
    • Seattle, Washington, United States, 98105
      • Recruiting
      • Seattle Children's Hospital
      • Contact: Gary Stobbe, MD; Phone Number: 206-987-8080

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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)
• Has a body mass index (BMI) 18 through 34 kg/m², inclusive
• Full scale IQ (or equivalent) ≥55 score, with adequate verbal fluency, as determined by the Principal Investigator.
• 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 ≥140 mmHg (if adult) or >135 mmHg (if adolescent), or diastolic blood pressure ≥90 (if adult) or >85 mmHg (if adolescent), or a clinical history of uncontrolled or severe hypertension
• If female, is pregnant or lactating

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: ML-004 (IR)/(ER) tablet; 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; Participants will receive ML-004 once daily.
Placebo Comparator: ML-004 Placebo; 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; Participants will receive matching placebo once daily.

What is the study measuring?

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 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-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 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
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 at all 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 ABI Repetitive/Restrictive Behavior Domain Score	Each item on the ABI-Repetitive/Restrictive Behavior Domain is rated by frequency (never to 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 (never to 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 (never to 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 (never to 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 ABC-Social Withdrawal (ABC-SW) Subscale Score	The ABC-SW subscale consists of 16 items of the ABC-2 rated from 0 (not at all a problem) to 3 (the problem is severe in degree).	Baseline up to Day 110

Collaborators and Investigators

• Sponsor: MapLight Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2022
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): April 30, 2025

Study Registration Dates

• First Submitted: October 5, 2021
• First Submitted That Met QC Criteria: October 5, 2021
• First Posted (Actual): October 18, 2021

Study Record Updates

• Last Update Posted (Estimated): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: ASD; Autism; Autism Spectrum Disorder; Social Communication
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
• Other Study ID Numbers: ML-004-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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