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)
- Registration Number
- NCT04299464
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 104
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants will receive placebo matched to RO7017773 for approximately 12 weeks. RO7017773 Low Dose RO7017773 Participants will receive a fixed low dose of RO7017773 for approximately 12 weeks. RO7017773 High Dose RO7017773 Participants will receive a fixed high dose of RO7017773 for approximately 12 weeks.
- Primary Outcome Measures
Name Time Method Change From Baseline to Week 12 in the Adaptive Behavior Composite (ABC) Score of the Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Baseline to Week 12 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.
- Secondary Outcome Measures
Name Time Method Number of Participants With at Least One Adverse Events (AEs) Up to Week 18 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.
Number of Participants With at Least One Serious Adverse Events (SAEs) Up to Week 18 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.
Number of Participants Discontinuing Treatment Due to AEs Day 1 up to Week 12 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.
Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behaviour as Measured Using the Columbia-Suicide-Severity Rating Scale (C-SSRS) Baseline up to Week 18 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.
Change From Baseline in Karolinska Sleepiness Scale (KSS) Score for Assessing Daytime Sleepiness 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 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.
Change From Baseline in Epworth Sleepiness Scale Score (ESS) for Assessing Daytime Sleepiness Baseline (Day 1), Days 14, 42, and 84 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.
Change From Baseline ESS Score for Children and Adolescents (ESS-CHAD) for Assessing Daytime Sleepiness Baseline (Day 1), Days 14, 42, 63, and 84 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.
Number of Participants With Daytime Sleepiness Assessed Using Sudden Onset of Sleep Questionnaire Baseline (Day 1), Days 7, 14, 42, 63, and 84 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.
Change From Baseline to Week 12 in Behavior/Symptoms as Measured by All Domains of the Repetitive Behavior Scale-Revised (RBS-R) Score Baseline to Week 12 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.
Change From Baseline to Week 12 on the Vineland-3 Socialization Domain Baseline to Week 12 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.
Change From Baseline to Week 12 on the Vineland-3 Communication Domain Baseline to Week 12 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.
Trial Locations
- Locations (21)
Ist. G. Gaslini
🇮🇹Genova, Liguria, Italy
Istituto Scientifico Medea
🇮🇹Bosisio Parini (LC), Lombardia, Italy
P.O. Gaspare Rodolico
🇮🇹Catania, Sicilia, Italy
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
University Hospitals
🇺🇸Cleveland, Ohio, United States
IGAIN (Instituto Global de Atención Integral al Neurodesarrollo)
🇪🇸Barcelona, Spain
APG- Advanced Psychiatric Group
🇺🇸Orlando, Florida, United States
Janeway Childrens Health
🇨🇦St. John's, Newfoundland and Labrador, Canada
Holland Bloorview Kids Rehabilitation Hospital
🇨🇦East York, Ontario, Canada
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Southwest Autism Research and Resource Center
🇺🇸Phoenix, Arizona, United States
Yale University / Yale-New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Nathan Kline Institute
🇺🇸Orangeburg, New York, United States
UPMC Western Psychiatric Institute and Clinic
🇺🇸Pittsburgh, Pennsylvania, United States
Vanderbilt Medical Center
🇺🇸Nashville, Tennessee, United States
Okanagan Clinical Trials
🇨🇦Kelowna, British Columbia, Canada