Clinical trial NCT01793441: A Study of RG7314 to Investigate Efficacy and Safety in Individuals With Autism Spectrum Disorders (ASD)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autism Spectrum Disorder
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-02-15
Enrollment: 223
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Social Communication Deficits as Measured by Social Responsiveness Scale 2 (SRS-2)
timeFrame: Baseline, Week 12
measure: Percentage of Participants with Suicidality, as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline up to Week 12
measure: Percentage of Participants With Adverse Events
timeFrame: From Baseline up to Week 18
Secondary outcomes:
measure: Change From Baseline in Behavior/Symptoms as Measured by Aberrant Behavior Checklist (ABC)
timeFrame: Baseline, Week 12
measure: Change From Baseline in Behavior/Symptoms as Measured by Repetitive Behavior Scale-Revised (RBS-R)
timeFrame: Baseline, Week 12
measure: Change From Baseline in Behavior/Symptoms as Measured by Anxiety, Depression and Mood Scale (ADAMS)
timeFrame: Baseline, Week 12
measure: Measure: Change From Baseline in Behavior/Symptoms as Measured by State-Trait Anxiety Inventory (STAI)
timeFrame: Baseline, Week 12
measure: Change From Baseline in Clinical Global Impressions as Measured by Clinical Global Impressions Improvement (CGI-I) Scale
timeFrame: Baseline, Week 12
measure: Change From Baseline in Adaptive Functioning and Skills as Measured by Vineland-II Adaptive Behavior Scale (VABS)
timeFrame: Baseline, Week 12
measure: Plasma Concentration of RG7314
timeFrame: 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)
measure: Plasma Concentration of RG7314 Metabolite M3
timeFrame: 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)
measure: Area Under the Plasma Concentration Versus Time Curve From Time Zero to Last Measurable Concentration (AUClast) of RG7314
timeFrame: 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)
measure: AUClast of RG7314 Metabolite M3
timeFrame: 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)
measure: Maximum Observed Plasma Concentration (Cmax) of RG7314
timeFrame: 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)
measure: Cmax of RG7314 Metabolite M3
timeFrame: 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)
measure: 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
timeFrame: From Baseline to Week 12
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Southwest Autism Research & Resource Center
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
facility: PCSD Feighner Research
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: San Francisco
country: United States
state: California
city: Santa Ana
country: United States
state: California
city: Stanford
country: United States
state: California
city: Centennial
country: United States
facility: DBA IMMUNOe Int'l Res Center
state: Colorado
city: Centennial
country: United States
state: Colorado
city: New Haven
country: United States
facility: Yale University; Yale Child Study Center
state: Connecticut
city: New Haven
country: United States
state: Connecticut
city: Delray Beach
country: United States
facility: Neurology offices of south florida
state: Florida
city: Delray Beach
country: United States
state: Florida
city: Oakland Park
country: United States
facility: Research Centers of America, LLC
state: Florida
city: Oakland Park
country: United States
state: Florida
city: Orlando
country: United States
facility: Compass Research
state: Florida
city: Orlando
country: United States
state: Florida
city: Decatur
country: United States
facility: Emory University School of Medicine; Department of Human Genetics & Pediatrics
state: Georgia
city: Decatur
country: United States
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
state: Illinois
city: Baltimore
country: United States
facility: The Kennedy Krieger Institute
state: Maryland
city: Baltimore
country: United States
state: Maryland
city: Rockville
country: United States
facility: Neuroscientific Insights
state: Maryland
city: Rockville
country: United States
state: Maryland
city: Lexington
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Lexington
country: United States
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota; Clin. Neuro Research Unit
state: Minnesota
city: Minneapolis
country: United States
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Medical Center; Departments of Psychiatry & Biobehavioral Science
state: New York
city: Bronx
country: United States
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine; Seaver Autism Center
state: New York
city: New York
country: United States
state: New York
city: Orangeburg
country: United States
facility: Nathan S. Kline Institute for Psychiatric Research
state: New York
city: Orangeburg
country: United States
state: New York
city: Durham
country: United States
facility: DUKE SCHOOL OF MEDICINE;Duke Center for Autism and Brain Development
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Western Psychiatric Institute and Clinic
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Medical Center
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: San Antonio
country: United States
facility: Road Runner Research
state: Texas
city: San Antonio
country: United States
state: Texas
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Bellevue
country: United States
state: Washington
city: Bothell
country: United States
facility: Pacific Institute of Medical Sciences
state: Washington
city: Bothell
country: United States
state: Washington
city: Seattle
country: United States
facility: Seattle Children's Research Institute
state: Washington
city: Seattle
country: United States
state: Washington
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: