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

• ClinicalTrials.gov Identifier: NCT05081245
• Recruitment Status: Recruiting
• First Posted: October 18, 2021
• Last Update Posted: May 1, 2024
• Sponsor: MapLight Therapeutics
• Information provided by (Responsible Party): MapLight Therapeutics

Tracking Information

• First Submitted Date: October 5, 2021
• First Posted Date: October 18, 2021
• Last Update Posted Date: May 1, 2024
• Actual Study Start Date: September 13, 2022
• Estimated Primary Completion Date: March 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 5, 2021)

Change from Baseline in Autism Behavior Inventory (ABI)-Social Communication Domain Score [ Time Frame: Baseline up to Day 110 ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 9, 2024)

• Change from Baseline in Clinician Global Impression of Improvement (CGI-I) [ Time Frame: Day 110 ]
  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).
• Change from Baseline in Autism Behavior Inventory-Clinician (ABI-C) Score [ Time Frame: Baseline up to Day 110 ]
  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).
• Change from Baseline in Aberrant Behavior Checklist 2-Irritability (ABC-I) Subscale Score [ Time Frame: Baseline up to Day 110 ]
  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.
• Change from baseline in the Clinician Global Impression of Severity (CGI-S) Score [ Time Frame: Baseline up to Day 110 ]
  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).
• Change from baseline in the ABI Repetitive/Restrictive Behavior Domain Score [ Time Frame: Baseline up to Day 110 ]
  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.
• Change from baseline in the ABI Mood and Anxiety Domain Score [ Time Frame: Baseline up to Day 110 ]
  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.
• Change from baseline in the ABI Challenging Behavior Domain Score [ Time Frame: Baseline up to Day 110 ]
  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.
• Change from baseline in the ABI Self-regulation Domain Score [ Time Frame: Baseline up to Day 110 ]
  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.
• Change from baseline in the ABI-Short Form (ABI-S) Score [ Time Frame: Baseline up to Day 110 ]
  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.
• Change from baseline in the ABC-Social Withdrawal (ABC-SW) Subscale Score [ Time Frame: Baseline up to Day 110 ]
  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).
• Change from baseline in the Social Responsiveness Scale 2 (SRS-2) Score [ Time Frame: Baseline up to Day 110 ]
  The SRS-2 consists of 65 items across 5 subscales. Responses range from 1 (not true) to 4 (almost always true).
• Change from baseline in the Vineland-3 (Domain Level Version) Score: total of Communication, Socialization, and Maladaptive behavior domains [ Time Frame: Baseline up to Day 110 ]
  The Vineland-3 Domain Level Version contains 5 domains. Responses on each item are rated from 0 (never) to 2 (usually).

Original Secondary Outcome Measures (submitted: October 5, 2021)

• Change from Baseline in Clinician Global Impression of Improvement (CGI-I) [ Time Frame: Day 110 ]
  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).
• Change from Baseline in Autism Behavior Inventory-Clinician (ABI-C) Score [ Time Frame: Baseline up to Day 110 ]
  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).
• Change from Baseline in Aberrant Behavior Checklist 2-Irritability (ABC-I) Subscale Score [ Time Frame: Baseline up to Day 110 ]
  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.
• Change from baseline in the Clinician Global Impression of Severity (CGI-S) Score [ Time Frame: Baseline up to Day 110 ]
  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).
• Change from baseline in the ABI Repetitive/Restrictive Behavior Domain Score [ Time Frame: Baseline up to Day 110 ]
  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.
• Change from baseline in the ABI Mood and Anxiety Domain Score [ Time Frame: Baseline up to Day 110 ]
  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.
• Change from baseline in the ABI Challenging Behavior Domain Score [ Time Frame: Baseline up to Day 110 ]
  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.
• Change from baseline in the ABI Self-regulation Domain Score [ Time Frame: Baseline up to Day 110 ]
  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.
• Change from baseline in the ABI-Short Form (ABI-S) Score [ Time Frame: Baseline up to Day 110 ]
  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.
• Change from baseline in the ABC-Social Withdrawal (ABC-SW) Subscale Score [ Time Frame: Baseline up to Day 110 ]
  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).
• Change from baseline in the Social Responsiveness Scale 2 (SRS-2) Score [ Time Frame: Baseline up to Day 110 ]
  The SRS-2 consists of 65 items across 5 subscales. Responses range from 1 (not true) to 4 (almost always true).
• Change from baseline in the Vineland-3 (Domain Level Version) Score: total of Communication, Socialization, and Maladaptive behavior domains [ Time Frame: Baseline up to Day 110 ]
  The Vineland-3 Domain Level Version contains 5 domains. Responses on each item are rated from 0 (never) to 2 (usually).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: ML-004 in Adolescents and Adults With Autism Spectrum Disorders (ASD)
• Official Title: 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).
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Multi-center, randomized, double-blind, placebo-controlled study

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Double-blind

Primary Purpose: Treatment

• Condition: Autism Spectrum Disorder

Intervention

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

Study Arms

• 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).
  Intervention: Drug: ML-004 (IR)/(ER) tablet
• 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).
  Intervention: Drug: ML-004 Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 5, 2021): 150
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 30, 2025
• Estimated Primary Completion Date: March 31, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 45 Years (Child, Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Alexis Levine; +1 650-839-4388; alevine@maplightrx.com

• Listed Location Countries: Australia, Canada, United States

Administrative Information

• NCT Number: NCT05081245
• Other Study ID Numbers: ML-004-002
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: MapLight Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: MapLight Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: MapLight Therapeutics
• Verification Date: April 2024