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

Autism Spectrum Disorder Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01793441
• Other study ID #: BP28420
• Secondary ID: 2012-005597-55
• Status: Completed
• Phase: Phase 2
• First received: February 14, 2013
• Last updated: February 2, 2017
• Start date: September 2013
• Est. completion date: September 2016

Study information

• Verified date: January 2017
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 223
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder
• Child Development Disorders, Pervasive
• Disease

Intervention

Drug:
• Placebo
Placebo will be administered in different stages of the study for 12 weeks.
• 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.

Locations

Country	Name	City	State
United States	The Kennedy Krieger Institute	Baltimore	Maryland
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Pacific Institute of Medical Sciences	Bothell	Washington
United States	Montefiore Medical Center; Departments of Psychiatry & Biobehavioral Science	Bronx	New York
United States	DBA IMMUNOe Int'l Res Center	Centennial	Colorado
United States	Rush University Medical Center	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University Hospitals	Cleveland	Ohio
United States	Emory University School of Medicine; Department of Human Genetics & Pediatrics	Decatur	Georgia
United States	Neurology offices of south florida	Delray Beach	Florida
United States	DUKE SCHOOL OF MEDICINE;Duke Center for Autism and Brain Development	Durham	North Carolina
United States	Massachusetts General Hospital	Lexington	Massachusetts
United States	University of Minnesota; Clin. Neuro Research Unit	Minneapolis	Minnesota
United States	Vanderbilt Medical Center	Nashville	Tennessee
United States	Yale University; Yale Child Study Center	New Haven	Connecticut
United States	Mount Sinai School of Medicine; Seaver Autism Center	New York	New York
United States	Research Centers of America, LLC	Oakland Park	Florida
United States	Nathan S. Kline Institute for Psychiatric Research	Orangeburg	New York
United States	Compass Research	Orlando	Florida
United States	Southwest Autism Research & Resource Center	Phoenix	Arizona
United States	UPMC Western Psychiatric Institute and Clinic	Pittsburgh	Pennsylvania
United States	Neuroscientific Insights	Rockville	Maryland
United States	University of California Davis	Sacramento	California
United States	Road Runner Research	San Antonio	Texas
United States	PCSD Feighner Research	San Diego	California
United States	University of California at San Francisco	San Francisco	California
United States	Seattle Children's Research Institute	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Social Communication Deficits as Measured by Social Responsiveness Scale 2 (SRS-2)		Baseline, Week 12
Primary	Percentage of Participants with Suicidality, as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)		Baseline up to Week 12
Primary	Percentage of Participants With Adverse Events		From Baseline up to Week 18
Secondary	Change From Baseline in Behavior/Symptoms as Measured by Aberrant Behavior Checklist (ABC)		Baseline, Week 12
Secondary	Change From Baseline in Behavior/Symptoms as Measured by Repetitive Behavior Scale-Revised (RBS-R)		Baseline, Week 12
Secondary	Change From Baseline in Behavior/Symptoms as Measured by Anxiety, Depression and Mood Scale (ADAMS)		Baseline, Week 12
Secondary	Measure: Change From Baseline in Behavior/Symptoms as Measured by State-Trait Anxiety Inventory (STAI)		Baseline, Week 12
Secondary	Change From Baseline in Clinical Global Impressions as Measured by Clinical Global Impressions Improvement (CGI-I) Scale		Baseline, Week 12
Secondary	Change From Baseline in Adaptive Functioning and Skills as Measured by Vineland-II Adaptive Behavior Scale (VABS)		Baseline, Week 12
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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