A 12-Week Crossover Study to Assess the Efficacy, Safety and Tolerability of L1-79 in Subjects Aged 12-21 Years With Autism Spectrum Disorder

A Randomized, Double-Blind, Chronic Dosing (12-weeks), Two-Period, Placebo-Controlled, Crossover, Multi-Center Study to Assess the Efficacy, Safety, and Tolerability of Two Doses of L1-79 for the Treatment of the Core Deficits in Social-Communication Interaction in Adolescents and Young Adults With Autism Spectrum Disorder

This study will investigate the efficacy, safety and tolerability of L1-79 in participants aged 12-21 years who have been diagnosed with ASD with a score of >/= 70 on the Wechsler Abbreviated Scale of Intelligence (WASI-II), and a score of >/= 4 on the Clinical Global Impression of Severity of Illness (CGI-S) weighted for socialization.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorder; Autism
• Intervention / Treatment: Drug: L1-79

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Southwest Autism Research and Resource Center
  • California
    • Orange, California, United States, 92868
      • Thompson Autism Center CHOC
    • San Rafael, California, United States, 94093
      • Cortica
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University
  • Missouri
    • Columbia, Missouri, United States, 65211
      • Thompson Center for Autism and Neurodevelopmental Disorders
  • New York
    • White Plains, New York, United States, 10032
      • Center for Autism and the Developing Brain
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Texas
    • Houston, Texas, United States, 77090
      • Red Oak Psychiatry Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female adolescents or young adults between 12 and 21 years of age.
• WASI-II standard score with 95% CI containing 70 or greater at screening or within the last 12 months prior to screening.
• Fulfill language criteria required to complete ADOS-2 Modules 2, 3 or 4.
• Diagnosis of ASD based on tool that utilizes the DSM-5 criteria, confirmed with ADOS-2.
• CGI-S (weighted for socialization) of 4 or greater.
• A female is eligible to enter and participate in the study if she is of non-childbearing potential or childbearing potential, has negative pregnancy test at screening and, if sexually active, agrees to use acceptable contraception methods (defined in protocol), for the duration of the study and for at least 30 days after the last dose of study drug.
• Male subjects if sexually active and female partners of childbearing potential must agree to use acceptable contraceptive methods (defined in protocol), for the duration of the study and for at least 30 days after the last dose of study drug.
• Subjects and caregiver must be willing and able to participate in the testing procedures sufficient to obtain valid scores on the tests used herein.
• Must live with a parent/primary caregiver, or if not, during each week he/she must either spend at least 3 hours a day for at least 4 days or, spend the weekend with a parent/primary caregiver.
• In the opinion of the Investigator, be sufficiently tolerant and capable of complying with the requirements of this trial.
• Able to swallow study medication whole and self-administer medication if living independently or have a parent/caregiver be able to administer medication.
• Subjects or their legal guardians must be willing to sign informed consent and/or assent and caregivers participating in the study must be willing to sign informed consent.

Exclusion Criteria:

• Pregnancy or breastfeeding, or intention to become pregnant during the study.
• Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic cardio-vascular disease, hepatic disease, renal disease, musculo skeletal or rheumatologic disease, human immunodeficiency virus (HIV), hemorrhagic cerebrovascular accident (HCVA), hepatitis B virus (HBV), or psychiatric illness/social situations that would limit compliance with study requirements.
• Any disease that requires treatment with immunosuppressive drugs.
• A diagnosis of Fragile-X syndrome or Rett syndrome.
• A DSM-5 diagnosis of schizophrenia, schizoaffective disorder, alcohol use disorder, current or lifetime diagnosis of severe psychiatric disorder (e.g., bipolar disorder, etc.).
• Subjects at risk of suicidal behavior or with a history alcohol or substance abuse/dependence.
• Presence of any active chronic medical problem including, but not limited to uncontrolled: seizure disorder, heart disease, cancer, asthma, genetic disease.
• Requiring more than 3 medications for the treatment of autism, ADHD, seizures, depression, anxiety, aggression, agitation, obsessive compulsive disorder, tic disorder, or other disorder commonly co-occurring with ASD.
• Initiation of new or major change in psychosocial intervention within 12 weeks prior to screening and throughout the duration of the study.
• School or academic setting are expected to change during the course the study.
• Clinically significant ECG abnormalities including subjects with baseline QTc prolongation (QTcF >450 msec for males and >470 msec in females).
• On concomitant medications known to prolong the QTc interval.
• Presence of out of range hepatic or renal function tests or other unexplained abnormal laboratory value that is deemed clinically significant by the Investigator.
• On any of the following medications: alpha-2 agonists (including, but not limited to clonidine and guanfacine), beta-blockers, anti-hypertensives, and antipsychotics not approved for use in ASD.
• Taking disallowed concomitant medications within 2 months (antipsychotics) and 1 month (all other medications) prior to Baseline.
• Any subject or caregiver who is unwilling or unable to give informed consent.
• Participated in an investigational drug study within 90 days prior to Baseline.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Capsules; 1 capsule twice daily	Drug: L1-79; tyrosine hydroxylase inhibitor; Other Names: DL-alpha-Methyltyrosine
Experimental: L1-79 200 mg or 300 mg Capsules; 1 capsule twice daily	Drug: L1-79; tyrosine hydroxylase inhibitor; Other Names: DL-alpha-Methyltyrosine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vineland Adaptive Behavior Scale, Third Edition (Vineland-3), Responder Analysis	at least 1 point improvement in 2/3 socialization subdomains or at least 3 point improvement in socialization domain	Week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Caregiver Global Impression of Change of 3 Most Bothersome Symptoms of ASD (CGI-3P)	Week 12
Social Responsiveness Scale, Second Edition (SRS-2) Social-Communication and Interaction - DSM-5 Composite T-score	Week 12
Social Responsiveness Scale, Second Edition (SRS-2) Total T-score	Week 12
Social Responsiveness Scale, Second Edition (SRS-2) Social Motivation T-score	Week 12
Vineland-3 Socialization Domain, Standard Score	Week 12
Parent-rated Anxiety Scale for ASD (PRAS-ASD)	Week 12
Child's Sleep Habits Questionnaire (CSHQ)	Week 12
V-scale Score for Each of the 3 Socialization Subdomains of the Vineland-3	Week 12
Clinical Global Impression of Severity of Illness (CGI-S) Weighted for Socialization	Week 12
Clinical Global Impression of Change (CGI-C) Weighted for Socialization	Week 12
Growth Scale Value (GSV) of Each of the 3 Socialization Subdomains of the Vineland-3	Week 12
Social Responsiveness Scale, Second Edition (SRS-2) Social Awareness T-score	Week 12
Social Responsiveness Scale, Second Edition (SRS-2) Social Cognition T-score	Week 12
Social Responsiveness Scale, Second Edition (SRS-2) Social Communication T-score	Week 12
Aberrant Behavior Checklist, Second Edition (ABC-2) Social Withdrawal/Lethargy Subscale	Week 12
Aberrant Behavior Checklist, Second Edition (ABC-2) Inappropriate Speech Subscale	Week 12

Collaborators and Investigators

• Sponsor: Yamo Pharmaceuticals LLC
• Investigators: Study Director: Tom Megerian, MD, PhD, CMO and Senior VP of Clinical Development

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2022
• Primary Completion (Actual): June 18, 2024
• Study Completion (Actual): June 21, 2024

Study Registration Dates

• First Submitted: September 22, 2021
• First Submitted That Met QC Criteria: October 4, 2021
• First Posted (Actual): October 5, 2021

Study Record Updates

• Last Update Posted (Actual): July 31, 2024
• Last Update Submitted That Met QC Criteria: July 29, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; alpha-Methyltyrosine
• Other Study ID Numbers: Y202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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