A 12-Week Placebo-Controlled Study to Investigate the Efficacy, Safety, and Tolerability of RO7017773 in Participants Aged 15-45 Years With Autism Spectrum Disorder (ASD)

Hoffmann-La Roche104 enrolled

Overview

This study will investigate the efficacy, safety, tolerability, and pharmacokinetics of RO7017773 in participants aged 15-45 years who have been diagnosed with ASD with a score of \>/=50 on the Wechsler Abreviated Scale of Intelligence (WASI-II).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

104

Conditions

Autism Spectrum Disorder (ASD)

Interventions

PlaceboDRUG

Participants will receive oral placebo for approximately 12 weeks.

RO7017773DRUG

Participants will receive oral RO7017773 for approximately 12 weeks.

Eligibility

Sex: ALLMin age: 15 YearsMax age: 45 Years

Medical Language ↔ Plain English

Inclusion Criteria * Male and female participants with Autism Spectrum Disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) * Wechsler Abbreviated Scale of Intelligence (WASI-II) \>/= 50 at screening or within the last 12 months prior to screening * ASD or Autism diagnosis confirmed by Autism Diagnostic Observation Schedule (ADOS-2) * Body mass index within the range of 18.5 to 40 kg/m2 * Female Participants: is eligible if she is not pregnant, not breastfeeding, and women of childbearing potential (WOCBP), who agree to remain abstinent or use contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 28 days after the last dose of study drug * Language, hearing, and vision compatible with the study measurements as judged by the Investigator * Allowed existing treatment regimens should be stable for 8 weeks prior to screening. Investigator expects stability of these treatments and behavioral interventions for the duration of the study * In the Investigator's opinion, able to participate and deemed appropriate for participation in the study, capable of following the study SoA and able to comply with the study restrictions * In the Investigator's opinion, participation in the study or discontinuation of prohibited medication will not pose undue risks Exclusion Criteria Neurologic/Psychiatric Conditions: * Non-verbal individuals * Presence of chromosome 15q11.2 q13.1 duplication syndrome (Dup15q syndrome), known "syndromic" forms of ASD (confirmed per genetic results available at screening): fragile X syndrome, Prader Willi syndrome, Rett's syndrome, tuberous sclerosis, and Angelman syndrome, as well as genetic alterations strongly associated with ASD per genetic results available at screening affecting the following genes: CHD8, ANDP, SHANK3 * Medical history of alcohol and/or substance abuse/dependence in the last 12 months or positive test for drugs of abuse at screening * Initiation of a major change in psychosocial intervention within 6 weeks prior to screening. Minor changes in ongoing treatment are not considered major changes * Clinically significant psychiatric and/or neurological disorder that may interfere with the safety or efficacy endpoints * Risk of suicidal behavior in the opinion of a certified clinician or as evidenced by a "yes" to questions 4 and/or 5 of Columbia-Suicide-Severity Rating Scale (C-SSRS) taken at screening and baseline with respect to the last 12 months, or any suicide attempt in the past 5 years * Unstable epilepsy/seizure disorder within the past 6 months or changes in anticonvulsive therapy within the last 6 months Other Conditions: * Medical history of malignancy if not considered cured or if occurred within the last 3 years with the exception of fully excised non-melanoma skin cancers or in-situ carcinoma of the cervix that has been successfully treated * Concomitant disease, condition or treatment which would either interfere with the conduct of the study or pose an unacceptable risk to the participant in the opinion of the Investigator Prior/Concomitant Therapy * Use of prohibited medications or herbal remedies within 6 weeks or 5 half-lives (t1/2) prior to randomization Prior/Concurrent Clinical Study Experience: * Donation or loss of blood over 500 mL in adults and 250 mL in adolescents within 3 months prior to randomization * Participation in an investigational drug study within 1 month or 5 times the t1/2 of the investigational molecule prior to randomization or participation in a study testing an investigational medical device within 1 month prior to randomization or if the device is still active Diagnostic Assessments * Confirmed clinically significant abnormality in hematological, chemistry or coagulation laboratory parameters * Positive test result at screening for hepatitis B surface antigen, hepatitis C virus (HCV, untreated), or human immunodeficiency virus (HIV)-1 and -2. HCV participants who have been successfully treated and who test negative for HCV RNA, may be considered eligible for entry into the study Other Exculsions: * Uncorrected hypokalemia or hypomagnesaemia

Locations (21)

Southwest Autism Research and Resource Center

Phoenix, Arizona, United States

Outcomes

Primary Outcomes

Change From Baseline to Week 12 in the Adaptive Behavior Composite (ABC) Score of the Vineland Adaptive Behavior Scales, Third Edition (Vineland-3)

Vineland-3 is a semi-structured interview that measures an individual's adaptive behavior across 3 domains: Communication, Socialization, and Daily Living skills. Each domain is composed of 3 subdomains. Subdomain raw score is based on item responses (3-point scale: 0=never present; 1=sometimes present; 2=usually present) and is calculated for each subdomain of the three main domains as the sum of the scores for each item within the subdomain. Raw scores of the 9 subdomains are used to derive Growth Scale Values (GSVs; range = 10-197). A conversion table for mapping raw scores to GSV scores is found in Appendix 3, Table B.2 in the Vineland-3 manual (Sparrow et al. 2016). GSV is a person-ability score used to track an individual's progress. Vineland-3 ABC Composite GSV score is calculated as the mean GSV score (summing the 9 GSV subdomain scores and dividing by 9; Vineland-3 ABC Composite GSV scores can range from 10-154). A higher score indicates better adaptive functioning.

Time frame: Baseline to Week 12

Secondary Outcomes

Number of Participants With at Least One Adverse Events (AEs)

An AE is an untoward medical occurrence in a participant administered a pharmaceutical product and regardless of the causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product.

Time frame: Up to Week 18

Number of Participants With at Least One Serious Adverse Events (SAEs)

An AE is an untoward medical occurrence in a participant administered a pharmaceutical product and regardless of causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with the use of an investigational product, whether or not considered related to investigational product. A SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above.

Data from ClinicalTrials.gov

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Yale University / Yale-New Haven Hospital

New Haven, Connecticut, United States

APG- Advanced Psychiatric Group

Orlando, Florida, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Minnesota

Minneapolis, Minnesota, United States

Nathan Kline Institute

Orangeburg, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

University Hospitals

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

UPMC Western Psychiatric Institute and Clinic

Pittsburgh, Pennsylvania, United States

...and 11 more locations

Time frame: Up to Week 18

Number of Participants Discontinuing Treatment Due to AEs

Time frame: Day 1 up to Week 12

Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behaviour as Measured Using the Columbia-Suicide-Severity Rating Scale (C-SSRS)

C-SSRS=assessment tool used to assess lifetime suicidality of participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, and attempts with actual/potential lethality. Categories have binary responses (yes/no) and include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation/behavior is indicated by a "yes" answer to any of the listed categories. Score of 0 is assigned if no suicide risk is present. Score of 1 or higher= suicidal ideation or behavior. Categories with non-zero values are only reported here.

Time frame: Baseline up to Week 18

Change From Baseline in Karolinska Sleepiness Scale (KSS) Score for Assessing Daytime Sleepiness

The KSS measures the subjective level of sleepiness at a particular time during the day. On this scale, participants (or support persons for adolescents aged 15 to 17 years and low-functioning participants) indicate which level best reflects the psycho-physical state experienced in the last 5 minutes. The KSS is a 9-point scale (1=extremely alert, 9=very sleepy, great effort to keep awake, fighting sleep). A decrease in KSS score or negative change from baseline indicate an improvement in sleepiness.

Time frame: Baseline (Day 1 Predose), 3-4 hours post-dose on Day 1, Predose and 3-4 hours post-dose on Days 14, 42, and 84

Change From Baseline in Epworth Sleepiness Scale Score (ESS) for Assessing Daytime Sleepiness

The ESS is a brief, self-administered eight-item questionnaire that measures daytime sleepiness in adults. Participants were asked to rate on a scale of 0-3 the chances that, "over the past month" and "since last visit", he/she would have dozed in eight specific situations that are commonly met in daily life (0 = would never doze and 3 = high chance of dozing). The ESS score is the sum of eight item-scores and can range from 0 to 24. A lower ESS score or a negative change from baseline score indicates an improvement in daytime sleepiness.

Time frame: Baseline (Day 1), Days 14, 42, and 84

Change From Baseline ESS Score for Children and Adolescents (ESS-CHAD) for Assessing Daytime Sleepiness

The ESS-CHAD is a brief, support person-administered eight-item questionnaire that measures daytime sleepiness in children and adolescents. Each item asked the support persons of adolescents and participants with an IQ score \<70 to rate on a scale of 0-3 the chances that "Over the past month," and "since last visit", "your child" would have dozed in eight specific situations that are commonly met in daily life ( 0 to 3 where 0 = would never doze and 3 = high chance of dozing). The ESS score is the sum of eight item scores and can range from 0 to 24. A lower ESS score or negative change from baseline score indicates an improvement in daytime sleepiness.

Time frame: Baseline (Day 1), Days 14, 42, 63, and 84

Number of Participants With Daytime Sleepiness Assessed Using Sudden Onset of Sleep Questionnaire

A sleep questionnaire was developed specifically for this study. Each participant (or support person for adolescents aged 15 to 17 years and for low-functioning participants) was asked to answer a series of 8 questions. The questions and their corresponding responses are as follows: a. Have you ever fallen asleep or have you been likely to fall asleep during your waking time? (Yes/No); b. Was this episode? (Gradual with awareness/Sudden and unpredictable/Sudden with awareness); c. Of the recent episode, how often does this occur? (Every day/Less frequently/Once a week/Other); d. Do you feel worried about falling asleep during the day? (Yes/No); e. Did the episode (or episodes) disrupt your daily activities? (Considerably/Marginally/No); f. Did this episode (or episodes) disrupt your social life (Considerably/Marginally/No); g. In the case of such an episode, was awakening? (Difficult/Easy/Normal). Categories with non-zero values are only reported here.

Time frame: Baseline (Day 1), Days 7, 14, 42, 63, and 84

Change From Baseline to Week 12 in Behavior/Symptoms as Measured by All Domains of the Repetitive Behavior Scale-Revised (RBS-R) Score

The RBS-R is a 43-item informant-based questionnaire, assessing the variety of restricted and repetitive behaviors (RRBs) in individuals with ASD. The scale is grouped into six subscales: Stereotyped, Self-Injurious, Compulsive, Ritualistic, Sameness, and Restricted Behaviors. For each item, behaviors are rated on a 4-point scale: 0-Behavior does not occur, 1-Behavior occurs and is a mild problem, 2-Behavior occurs and is a moderate problem, 3-Behavior occurs and is a severe problem. A total RBS-R score is calculated as the sum of the scores for the 43 items. The total score ranges from 0 to 129 and higher scores are indicative of more severe RRBs.

Time frame: Baseline to Week 12

Change From Baseline to Week 12 on the Vineland-3 Socialization Domain

Vineland-3 is a semi-structured interview measuring an individual's adaptive behavior across 3 domains: Communication, Socialization \& Daily Living skills. Each domain consists of 3 subdomains. Subdomain raw scores are based on item responses (3-point scale: 0=never present; 1=sometimes present; 2=usually present) \& are calculated for each subdomain of Socialization (interpersonal relationships, play and leisure time, coping skills) domain as sum of the scores for each item in the subdomain. Raw scores for the 3 Socialization subdomains are used to derive GSVs (range=10-164). A conversion table for mapping raw scores to GSV scores is found in the Vineland-3 manual (Sparrow et al. 2016). GSV is a person-ability score used to track an individual's progress. Vineland-3 Socialization Domain GSV score is calculated as a mean GSV score (summing the 3 GSV subdomain scores \& dividing by 3). Vineland-3 Socialization Domain GSV score range = 10-145. Higher score =better adaptive functioning.

Time frame: Baseline to Week 12

Change From Baseline to Week 12 on the Vineland-3 Communication Domain

Vineland-3 is a semi-structured interview measuring an individual's adaptive behavior across 3 domains: Communication, Socialization \& Daily Living skills. Each domain consists of 3 subdomains. Subdomain raw scores are based on item responses (3-point scale: 0=never present; 1=sometimes present; 2=usually present) \& is calculated for each subdomain of the Communication (receptive, expressive, written) domain as the sum of the scores for each item within the subdomain. Raw scores for each of the 3 Communication subdomains are used to derive Growth Scale Values (GSVs; range from 10-197). A conversion table for mapping raw scores to GSV scores is found in Vineland-3 manual (Sparrow et al. 2016). GSV is a person-ability score used to track an individual's progress. Vineland-3 Socialization Domain GSV score is calculated as mean GSV score (summing the 3 GSV subdomain scores \& dividing by 3). Vineland-3 Socialization Domain GSV score range=10-174. Higher score=better adaptive functioning.

Time frame: Baseline to Week 12