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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Autism Spectrum Disorder, Autism

Intervention / Treatment
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* Drug: L1-79


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 21 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Two Period Crossover
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vineland Adaptive Behavior Scale, Third Edition (Vineland-3), Average of the Growth Scale Value (GSV) score of the three Socialization Subdomains (combined) |  | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brief Observation of Social Communication Change (BOSCC) |  | 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 | 
| Percent of subjects showing a statistically significant improvement in GSV on 2 of the Socialization Subdomains |  | Week 12 | 
| 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 |