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

A Multi-Center, Randomized, Double-Blind, 12-Week, Parallel Group, Placebo-Controlled Proof of Concept Study to Investigate the Efficacy and Safety of RG7314 in Individuals With Autism Spectrum Disorders (ASD)

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.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Drug: Placebo; Drug: RG7314

• Study Type: Interventional
• Enrollment (Actual): 223
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
    • Phoenix, Arizona, United States, 85006
      • Southwest Autism Research & Resource Center
  • California
    • Sacramento, California, United States, 95817
      • University of California Davis
    • Sacramento, California, United States, 95817
    • San Diego, California, United States, 92108
    • San Diego, California, United States, 92108
      • PCSD Feighner Research
    • San Francisco, California, United States, 94115
    • San Francisco, California, United States, 94115
      • University of California at San Francisco
    • Santa Ana, California, United States, 92705
    • Stanford, California, United States, 94305
  • Colorado
    • Centennial, Colorado, United States, 80112
    • Centennial, Colorado, United States, 80112
      • DBA IMMUNOe Int'l Res Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
    • New Haven, Connecticut, United States, 06510
      • Yale University; Yale Child Study Center
  • Florida
    • Delray Beach, Florida, United States, 33445
    • Delray Beach, Florida, United States, 33445
      • Neurology Offices of South Florida
    • Oakland Park, Florida, United States, 33334
    • Oakland Park, Florida, United States, 33334
      • Research Centers of America, LLC
    • Orlando, Florida, United States, 32806
    • Orlando, Florida, United States, 32806
      • Compass Research
  • Georgia
    • Decatur, Georgia, United States, 30033
    • Decatur, Georgia, United States, 30033
      • Emory University School of Medicine; Department of Human Genetics & Pediatrics
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60612
  • Maryland
    • Baltimore, Maryland, United States, 21205
    • Baltimore, Maryland, United States, 21205
      • The Kennedy Krieger Institute
    • Rockville, Maryland, United States, 20852
      • Neuroscientific Insights
    • Rockville, Maryland, United States, 20852
  • Massachusetts
    • Lexington, Massachusetts, United States, 02421
    • Lexington, Massachusetts, United States, 02421
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
    • Minneapolis, Minnesota, United States, 55414
      • University of Minnesota; Clin. Neuro Research Unit
  • New York
    • Bronx, New York, United States, 10467
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center; Departments of Psychiatry & Biobehavioral Science
    • New York, New York, United States, 10029
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine; Seaver Autism Center
    • Orangeburg, New York, United States, 10962
      • Nathan S. Kline Institute for Psychiatric Research
    • Orangeburg, New York, United States, 10962
  • North Carolina
    • Durham, North Carolina, United States, 27705
    • Durham, North Carolina, United States, 27705
      • DUKE SCHOOL OF MEDICINE;Duke Center for Autism and Brain Development
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cincinnati, Ohio, United States, 45229
    • Cleveland, Ohio, United States, 44106
      • University Hospitals
    • Cleveland, Ohio, United States, 44106
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15203 1101
      • UPMC Western Psychiatric Institute and Clinic
    • Pittsburgh, Pennsylvania, United States, 15203 1101
  • Tennessee
    • Nashville, Tennessee, United States, 37232
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Medical Center
  • Texas
    • San Antonio, Texas, United States, 78258
    • San Antonio, Texas, United States, 78258
      • Road Runner Research
  • Washington
    • Bellevue, Washington, United States, 98007
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • Bothell, Washington, United States, 98011
      • Pacific Institute Of Medical Sciences
    • Bothell, Washington, United States, 98011
    • Seattle, Washington, United States, 98145
      • Seattle Children's Research Institute
    • Seattle, Washington, United States, 98145

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Participants will receive placebo matching to RG7314 in each stage (Stage I, II, III and IV) for 12 weeks.	Drug: Placebo; Placebo will be administered in different stages of the study for 12 weeks.
EXPERIMENTAL: RG7314; Participants 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.	Drug: RG7314; RG7314 will be administered 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Events	From Baseline up to Week 18

Secondary Outcome Measures

Outcome Measure	Time Frame
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 Repetitive Behavior Scale-Revised (RBS-R)	Baseline, Week 12
Change From Baseline in Behavior/Symptoms as Measured by Anxiety, Depression and Mood Scale (ADAMS)	Baseline, Week 12
Measure: Change From Baseline in Behavior/Symptoms as Measured by State-Trait Anxiety Inventory (STAI)	Baseline, Week 12
Change From Baseline in Clinical Global Impressions as Measured by Clinical Global Impressions Improvement (CGI-I) Scale	Baseline, Week 12
Change From Baseline in Adaptive Functioning and Skills as Measured by Vineland-II Adaptive Behavior Scale (VABS)	Baseline, Week 12
Plasma Concentration of RG7314	Pre-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)
Plasma Concentration of RG7314 Metabolite M3	Pre-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 RG7314	Pre-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)
AUClast of RG7314 Metabolite M3	Pre-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)
Maximum Observed Plasma Concentration (Cmax) of RG7314	Pre-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)
Cmax of RG7314 Metabolite M3	Pre-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 2	From Baseline to Week 12

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (ACTUAL): September 1, 2016
• Study Completion (ACTUAL): September 1, 2016

Study Registration Dates

• First Submitted: February 14, 2013
• First Submitted That Met QC Criteria: February 14, 2013
• First Posted (ESTIMATE): February 15, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): February 3, 2017
• Last Update Submitted That Met QC Criteria: February 2, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
• Other Study ID Numbers: BP28420; 2012-005597-55 (EUDRACT_NUMBER)