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A Study of RG7314 to Investigate Efficacy and Safety in Individuals With Autism Spectrum Disorders (ASD)

Phase 2
Completed
Conditions
Autism Spectrum Disorder
Interventions
Drug: Placebo
Registration Number
NCT01793441
Lead Sponsor
Hoffmann-La Roche
Brief Summary

This multi-center, randomized, double-blind, parallel group, placebo-controlled, proof of concept study will investigate the efficacy and safety of RG7314 in adult participants with ASD. In Stage I of the study, participants will be randomized in 2:1 to receive daily oral doses of 1.5 milligrams (mg) RG7314 or placebo for 12 weeks. After an independent safety review, the study may proceed to Stage II. In Stage II of the study, additional participants will be randomized in 2:1 to receive daily oral doses of 4 mg RG7314 or placebo for 12 weeks. After an independent safety review, Stage III will be started wherein additional participants will be randomized in 2:1 to receive daily oral doses of 10 mg RG7314 or placebo for 12 weeks. During Stage III, safety will be reviewed by independent safety review twice and if no safety signal is observed, then additional participants will be randomized in 1:1:1 either to receive 1.5 milligrams per day (mg/day) or 10 mg/day RG7314 orally or placebo for 12 weeks in Stage IV.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
223
Inclusion Criteria
  • Participants meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for ASD and Tenth Revision of the International Classification of Diseases and Related Health Problems (ICD-10) criteria for Autism diagnosis
  • SRS-2 (T-score) greater than or equal to (>/=) 66
  • CGI-S >/=4 (moderately ill)
  • Participants have an Intelligence Quotient (IQ) >/=70 (Wechsler Abbreviated State of Intelligence)
  • A body mass index (BMI) between 18 to 40 kilograms per square meter (kg/m^2) inclusive
  • Language, hearing and vision compatible with the study measurements as judged by the investigator
  • Lives with (or has substantial periods of contact with) a caregiver who is willing and able to attend visits when required, oversee the participant's compliance with protocol-specified procedures and study medication dosing, and report on the participant's status via completion of study assessments. Any period of absence must be covered by another caregiver. Non-cohabitating caregiver(s) must spend sufficient time with the participant so that, in the opinion of the investigator, the caregiver(s) can reliably assess participant's mental status, activities and behavior.
Exclusion Criteria
  • Alcohol and/or substance abuse/dependence during the last 12 months
  • A significant risk for suicidal behavior, in the opinion of the investigator
  • Systolic blood pressure greater than (>) 140 or less than (<) 90 millimeters of mercury (mm Hg), and diastolic blood pressure >90 or less than (<) 50 mm Hg
  • Resting pulse rate >90 or <40 beats per minute
  • Use of prohibited medications or herbal remedies within 2 weeks prior to randomization, or 5 half-lives (whichever is longer)
  • Initiation of a new major change in psychological intervention within 4 weeks prior to randomization. Minor changes in ongoing treatment are not considered significant
  • Participation in an investigational drug or device study within 60 days prior to randomization

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
RG7314RG7314Participants will receive RG7314 orally at a dose of 1.5 mg/day in Stage I, 4 mg/day in Stage II, 10 mg/day in Stage III and 1.5 mg/day or 10 mg/day in Stage IV for 12 weeks.
PlaceboPlaceboParticipants will receive placebo matching to RG7314 in each stage (Stage I, II, III and IV) for 12 weeks.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Social Communication Deficits as Measured by Social Responsiveness Scale 2 (SRS-2)Baseline, Week 12
Percentage of Participants with Suicidality, as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)Baseline up to Week 12
Percentage of Participants With Adverse EventsFrom Baseline up to Week 18
Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Behavior/Symptoms as Measured by Aberrant Behavior Checklist (ABC)Baseline, Week 12
Change From Baseline in Behavior/Symptoms as Measured by Anxiety, Depression and Mood Scale (ADAMS)Baseline, Week 12
Plasma Concentration of RG7314 Metabolite M3Pre-dose (0 hr), and 2, 4, 6 hrs post-dose on Day 1, 14, 84; pre-dose (0 hr) on Day 42; any time during early withdrawal visit (up to Week 12)
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Last Measurable Concentration (AUClast) of RG7314Pre-dose (0 hr), and 2, 4, 6 hrs post-dose on Day 1, 14, 84; pre-dose (0 hr) on Day 42; any time during early withdrawal visit (up to Week 12)
Change From Baseline in Behavior/Symptoms as Measured by Repetitive Behavior Scale-Revised (RBS-R)Baseline, Week 12
Plasma Concentration of RG7314Pre-dose (0 hours [hr]), and 2, 4, 6 hrs post-dose on Day 1, 14, 84; pre-dose (0 hr) on Day 42; any time during early withdrawal visit (up to Week 12)
Cmax of RG7314 Metabolite M3Pre-dose (0 hr), and 2, 4, 6 hrs post-dose on Day 1, 14, 84; pre-dose (0 hr) on Day 42; any time during early withdrawal visit (up to Week 12)
Percentage of Participants With Clinical Response, Defined as At Least 25% Improvement in the SRS-2 Score With a CGI-I Score of 1 or 2From Baseline to Week 12
Change From Baseline in Clinical Global Impressions as Measured by Clinical Global Impressions Improvement (CGI-I) ScaleBaseline, Week 12
AUClast of RG7314 Metabolite M3Pre-dose (0 hr), and 2, 4, 6 hrs post-dose on Day 1, 14, 84; pre-dose (0 hr) on Day 42; any time during early withdrawal visit (up to Week 12)
Measure: Change From Baseline in Behavior/Symptoms as Measured by State-Trait Anxiety Inventory (STAI)Baseline, Week 12
Change From Baseline in Adaptive Functioning and Skills as Measured by Vineland-II Adaptive Behavior Scale (VABS)Baseline, Week 12
Maximum Observed Plasma Concentration (Cmax) of RG7314Pre-dose (0 hr), and 2, 4, 6 hrs post-dose on Day 1, 14, 84; pre-dose (0 hr) on Day 42; any time during early withdrawal visit (up to Week 12)

Trial Locations

Locations (27)

Neuroscientific Insights

🇺🇸

Rockville, Maryland, United States

University of California Davis

🇺🇸

Sacramento, California, United States

Montefiore Medical Center; Departments of Psychiatry & Biobehavioral Science

🇺🇸

Bronx, New York, United States

Compass Research

🇺🇸

Orlando, Florida, United States

Northwest Clinical Research Center

🇺🇸

Bellevue, Washington, United States

Research Centers of America, LLC

🇺🇸

Oakland Park, Florida, United States

Yale University; Yale Child Study Center

🇺🇸

New Haven, Connecticut, United States

University of California at San Francisco

🇺🇸

San Francisco, California, United States

UPMC Western Psychiatric Institute and Clinic

🇺🇸

Pittsburgh, Pennsylvania, United States

PCSD Feighner Research

🇺🇸

San Diego, California, United States

The Kennedy Krieger Institute

🇺🇸

Baltimore, Maryland, United States

Neurology offices of south florida

🇺🇸

Delray Beach, Florida, United States

Southwest Autism Research & Resource Center

🇺🇸

Phoenix, Arizona, United States

Emory University School of Medicine; Department of Human Genetics & Pediatrics

🇺🇸

Decatur, Georgia, United States

DUKE SCHOOL OF MEDICINE;Duke Center for Autism and Brain Development

🇺🇸

Durham, North Carolina, United States

Road Runner Research

🇺🇸

San Antonio, Texas, United States

University of Minnesota; Clin. Neuro Research Unit

🇺🇸

Minneapolis, Minnesota, United States

Seattle Children's Research Institute

🇺🇸

Seattle, Washington, United States

Vanderbilt Medical Center

🇺🇸

Nashville, Tennessee, United States

Massachusetts General Hospital

🇺🇸

Lexington, Massachusetts, United States

Mount Sinai School of Medicine; Seaver Autism Center

🇺🇸

New York, New York, United States

Nathan S. Kline Institute for Psychiatric Research

🇺🇸

Orangeburg, New York, United States

Cincinnati Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, United States

University Hospitals

🇺🇸

Cleveland, Ohio, United States

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

Pacific Institute of Medical Sciences

🇺🇸

Bothell, Washington, United States

DBA IMMUNOe Int'l Res Center

🇺🇸

Centennial, Colorado, United States

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