Clinical trial NCT05067582: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autism Spectrum Disorder
Autism
Lead sponsor: Yamo Pharmaceuticals LLC
Sponsor class: INDUSTRY
First posted: 2021-10-05
Enrollment: 58
Sex: ALL
Minimum age (years): 12
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Two Period Crossover
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Vineland Adaptive Behavior Scale, Third Edition (Vineland-3), Responder Analysis
timeFrame: Week 12
Secondary outcomes:
measure: Vineland-3 Socialization Domain, Standard Score
timeFrame: Week 12
measure: V-scale Score for Each of the 3 Socialization Subdomains of the Vineland-3
timeFrame: Week 12
measure: Clinical Global Impression of Severity of Illness (CGI-S) Weighted for Socialization
timeFrame: Week 12
measure: Clinical Global Impression of Change (CGI-C) Weighted for Socialization
timeFrame: Week 12
measure: Growth Scale Value (GSV) of Each of the 3 Socialization Subdomains of the Vineland-3
timeFrame: Week 12
measure: Caregiver Global Impression of Change of 3 Most Bothersome Symptoms of ASD (CGI-3P)
timeFrame: Week 12
measure: Social Responsiveness Scale, Second Edition (SRS-2) Social-Communication and Interaction - DSM-5 Composite T-score
timeFrame: Week 12
measure: Social Responsiveness Scale, Second Edition (SRS-2) Social Awareness T-score
timeFrame: Week 12
measure: Social Responsiveness Scale, Second Edition (SRS-2) Social Cognition T-score
timeFrame: Week 12
measure: Social Responsiveness Scale, Second Edition (SRS-2) Social Motivation T-score
timeFrame: Week 12
measure: Social Responsiveness Scale, Second Edition (SRS-2) Social Communication T-score
timeFrame: Week 12
measure: Social Responsiveness Scale, Second Edition (SRS-2) Total T-score
timeFrame: Week 12
measure: Parent-rated Anxiety Scale for ASD (PRAS-ASD)
timeFrame: Week 12
measure: Aberrant Behavior Checklist, Second Edition (ABC-2) Social Withdrawal/Lethargy Subscale
timeFrame: Week 12
measure: Aberrant Behavior Checklist, Second Edition (ABC-2) Inappropriate Speech Subscale
timeFrame: Week 12
measure: Child's Sleep Habits Questionnaire (CSHQ)
timeFrame: Week 12
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Southwest Autism Research and Resource Center
state: Arizona
city: Orange
country: United States
facility: Thompson Autism Center CHOC
state: California
city: San Rafael
country: United States
facility: Cortica
state: California
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Columbia
country: United States
facility: Thompson Center for Autism and Neurodevelopmental Disorders
state: Missouri
city: White Plains
country: United States
facility: Center for Autism and The Developing Brain
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Houston
country: United States
facility: Red Oak Psychiatry Associates
state: Texas
Study officials:
affiliation: CMO and Senior VP of Clinical Development
name: Tom Megerian, MD, PhD
role: STUDY_DIRECTOR
References: