Clinical trial NCT04299464: 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)
Official title: A Phase II Multicenter, Randomized, Double-Blind, 12-Week Treatment, 3-Arm, Parallel-Group, Placebo-Controlled Study to Investigate the Efficacy, Safety, and Tolerability of RO7017773 in Participants Aged 15-45 Years With Autism Spectrum Disorder (ASD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autism Spectrum Disorder (ASD)
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-03-06
Enrollment: 104
Sex: ALL
Minimum age (years): 15
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline to Week 12 in the Adaptive Behavior Composite (ABC) Score of the Vineland Adaptive Behavior Scales, Third Edition (Vineland-3)
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Number of Participants With at Least One Adverse Events (AEs)
timeFrame: Up to Week 18
measure: Number of Participants With at Least One Serious Adverse Events (SAEs)
timeFrame: Up to Week 18
measure: Number of Participants Discontinuing Treatment Due to AEs
timeFrame: Day 1 up to Week 12
measure: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behaviour as Measured Using the Columbia-Suicide-Severity Rating Scale (C-SSRS)
timeFrame: Baseline up to Week 18
measure: Change From Baseline in Karolinska Sleepiness Scale (KSS) Score for Assessing Daytime Sleepiness
timeFrame: 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
measure: Change From Baseline in Epworth Sleepiness Scale Score (ESS) for Assessing Daytime Sleepiness
timeFrame: Baseline (Day 1), Days 14, 42, and 84
measure: Change From Baseline ESS Score for Children and Adolescents (ESS-CHAD) for Assessing Daytime Sleepiness
timeFrame: Baseline (Day 1), Days 14, 42, 63, and 84
measure: Number of Participants With Daytime Sleepiness Assessed Using Sudden Onset of Sleep Questionnaire
timeFrame: Baseline (Day 1), Days 7, 14, 42, 63, and 84
measure: Change From Baseline to Week 12 in Behavior/Symptoms as Measured by All Domains of the Repetitive Behavior Scale-Revised (RBS-R) Score
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 on the Vineland-3 Socialization Domain
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 on the Vineland-3 Communication Domain
timeFrame: Baseline to Week 12
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Southwest Autism Research and Resource Center
state: Arizona
city: New Haven
country: United States
facility: Yale University / Yale-New Haven Hospital
state: Connecticut
city: Orlando
country: United States
facility: APG- Advanced Psychiatric Group
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Orangeburg
country: United States
facility: Nathan Kline Institute
state: New York
city: Cleveland
country: United States
facility: University Hospitals
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Western Psychiatric Institute and Clinic
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Medical Center
state: Tennessee
city: Kelowna
country: Canada
facility: Okanagan Clinical Trials
state: British Columbia
city: St. John's
country: Canada
facility: Janeway Childrens Health
state: Newfoundland and Labrador
city: East York
country: Canada
facility: Holland Bloorview Kids Rehabilitation Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Genova
country: Italy
facility: Ist. G. Gaslini
state: Liguria
city: Bosisio Parini (LC)
country: Italy
facility: Istituto Scientifico Medea
state: Lombardia
city: Catania
country: Italy
facility: P.O. Gaspare Rodolico
state: Sicilia
city: Barcelona
country: Spain
facility: IGAIN (Instituto Global de Atención Integral al Neurodesarrollo)
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: