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

• ClinicalTrials.gov Identifier: NCT05067582
• Recruitment Status: Recruiting
• First Posted: October 5, 2021
• Last Update Posted: March 9, 2022
• Sponsor: Yamo Pharmaceuticals LLC
• Information provided by (Responsible Party): Yamo Pharmaceuticals LLC

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Autism Spectrum Disorder; Autism	Drug: L1-79	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Two Period Crossover
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 25, 2022
• Estimated Primary Completion Date: February 2023
• Estimated Study Completion Date: March 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Vineland Adaptive Behavior Scale, Third Edition (Vineland-3), Average of the Growth Scale Value (GSV) score of the three Socialization Subdomains (combined) [ Time Frame: Week 12 ]

Secondary Outcome Measures :

1. Brief Observation of Social Communication Change (BOSCC) [ Time Frame: Week 12 ]
2. Clinical Global Impression of Severity of Illness (CGI-S) weighted for socialization [ Time Frame: Week 12 ]
3. Clinical Global Impression of Change (CGI-C) weighted for socialization [ Time Frame: Week 12 ]
4. Percent of subjects showing a statistically significant improvement in GSV on 2 of the Socialization Subdomains [ Time Frame: Week 12 ]
5. Caregiver Global Impression of Change of 3 Most Bothersome Symptoms of ASD (CGI-3P) [ Time Frame: Week 12 ]
6. Social Responsiveness Scale, Second Edition (SRS-2) Social-Communication and Interaction - DSM-5 Composite T-score [ Time Frame: Week 12 ]
7. Social Responsiveness Scale, Second Edition (SRS-2) Total T-score [ Time Frame: Week 12 ]
8. Social Responsiveness Scale, Second Edition (SRS-2) Social Motivation T-score [ Time Frame: Week 12 ]
9. Vineland-3 Socialization Domain, Standard Score [ Time Frame: Week 12 ]
10. Parent-rated Anxiety Scale for ASD (PRAS-ASD) [ Time Frame: Week 12 ]
11. Child's Sleep Habits Questionnaire (CSHQ) [ Time Frame: Week 12 ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Male or female adolescents or young adults between 12 and 21 years of age.
• WASI-II standard score ≥70 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.

Contacts and Locations

Contacts

Contact: Uyen Nguyen; 949-769-0046; unguyen@yamopharma.com

Contact: Tracy Fischer, PharmD; 859-685-5862; tfischer@yamopharma.com

Locations

United States, Arizona

Southwest Autism Research and Resource Center; Recruiting

Phoenix, Arizona, United States, 85006

Contact: Zakiyyah Merritt 480-701-3681 zmerritt@autismcenter.org

Principal Investigator: Raun Melmed, MD

United States, California

Thompson Autism Center CHOC; Recruiting

Orange, California, United States, 92868

Contact: Julie Hernandez 714-288-7683 jhernandez11@choc.org

Principal Investigator: Sailaja Golla, MD

United States, Illinois

Rush University; Recruiting

Chicago, Illinois, United States, 60612

Contact: Aneta Kwak Aneta_Z_Kwak@rush.edu

Principal Investigator: Cesar Ochoa-Lubinoff, MD

United States, Missouri

Thompson Center for Autism and Neurodevelopmental Disorders; Recruiting

Columbia, Missouri, United States, 65211

Contact: Kathy Hirst 573-882-5643 hirstka@missouri.edu

Principal Investigator: David Beversdorf, MD

United States, Texas

Red Oak Psychiatry Associates; Recruiting

Houston, Texas, United States, 77090

Contact: Thomas Vu 281-893-4111 ext 249 ropa29@earthlink.net

Principal Investigator: Lawrence Ginsberg, MD

Sponsors and Collaborators

Yamo Pharmaceuticals LLC

Investigators

• Study Director: Tom Megerian, MD, PhD; CMO and Senior VP of Clinical Development

More Information

• Responsible Party: Yamo Pharmaceuticals LLC
• ClinicalTrials.gov Identifier: NCT05067582
• Other Study ID Numbers: Y202
• First Posted: October 5, 2021
• Last Update Posted: March 9, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; alpha-Methyltyrosine; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action