A Study of RO5186582 in Down Syndrome Among Children 6 to 11 Years of Age

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group 26-Week Dose-Investigating Study to Explore the Pharmacokinetics, Pharmacodynamic Effects, Efficacy, Safety and Tolerability of RO5186582 in Children With Down Syndrome Aged 6-11 Years

This study will evaluate the safety, tolerability, efficacy, and pharmacokinetic and pharmacodynamic activity of 3 different dosages of RO5186582 compared with placebo. A total of approximately 46 participants will be enrolled, in order to have at least 32 evaluable, and will be randomly assigned to 1 of 4 treatments in a 1:1:1:1 ratio, with 9 children per treatment arm. The target ratio between 6-8 years and 9-11 years age groups is approximately 1:1 in each treatment arm, with a minimum of 3 children per age group in each treatment arm.

Study Overview

• Status: Terminated
• Conditions: Down Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: RO5186582

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Southwest Autism Research & Resource Center
  • Georgia
    • 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
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusette General Hospital; Medical Genetics
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital, Department of Neurology
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Clin Rsch Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15203 1101
      • UPMC Western Psychiatric Institute and Clinic
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of Down syndrome, except for mosaic Down syndrome
• Available parent or caregiver to attend clinic visits and provide information about the participant's behavior and symptoms

Exclusion Criteria:

• Any primary psychiatric comorbid disorder
• History of infantile spasms, West syndrome, Lennox-Gastaut syndrome, early infantile epileptic encephalopathy, treatment-refractory epilepsy with cognitive/developmental regression, severe head trauma, or central nervous system (CNS) infection
• Seizure event of any type within 12 months prior to Screening or relevant changes in anti-epileptic drugs 6 weeks prior to enrollment
• Significant sleep disruption
• Significant gastrointestinal, renal, hepatic, endocrine, or cardiovascular disease
• New-onset or ongoing hematologic/oncologic disorder
• Severe lactose intolerance
• Participation in another clinical study within 1 month or 6 half-lives prior to first dose, or any extent of participation in Study BP29589 (NCT02451657)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will receive matching placebo by mouth (PO) twice daily (BID) for up to 26 weeks.	Drug: Placebo; Participants will receive matching placebo PO BID. Study medication will first be administered on Day 1, and only the morning dose will be given on the last day of treatment (Week 26).
Experimental: RO5186582 120 mg BID; Participants will receive RO5186582 at a dosage of 120 milligrams (mg) PO BID for up to 26 weeks.	Drug: RO5186582; Participants will receive 1 of 3 dosages of RO5186582 PO BID, including 40 mg, 60 mg, or 120 mg. Study medication will first be administered on Day 1, and only the morning dose will be given on the last day of treatment (Week 26).
Experimental: RO5186582 40 mg BID; Participants will receive RO5186582 at a dosage of 40 mg PO BID for up to 26 weeks.	Drug: RO5186582; Participants will receive 1 of 3 dosages of RO5186582 PO BID, including 40 mg, 60 mg, or 120 mg. Study medication will first be administered on Day 1, and only the morning dose will be given on the last day of treatment (Week 26).
Experimental: RO5186582 60 mg BID; Participants will receive RO5186582 at a dosage of 60 mg PO BID for up to 26 weeks.	Drug: RO5186582; Participants will receive 1 of 3 dosages of RO5186582 PO BID, including 40 mg, 60 mg, or 120 mg. Study medication will first be administered on Day 1, and only the morning dose will be given on the last day of treatment (Week 26).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Adverse Events (AEs)	Baseline up to Week 6
Percentage of Participants With Epileptiform Abnormalities as Assessed Using Electroencephalogram (EEG) Analysis	Baseline up to Week 6
Percentage of Participants by Suicidality Classification as Assessed Using an Adapted Form of the Columbia Classification Algorithm for Suicide Assessment (C-CASA)	Baseline up to Week 6
Anxiety, Depression, and Mood Scale (ADAMS) Score	Baseline up to Week 6
Hyperactivity and Impulsivity as Assessed by the Short Version of Conners Third Edition Parent Short-Form (Conners-3) Score	Baseline up to Week 6
Sleep Disturbances as Assessed by the Children's Sleep Habits Questionnaire (CSHQ) Score	Baseline up to Week 6
Gamma Power at Posterior Electrodes as Assessed Using EEG Analysis	Baseline up to Week 6
Theta Power at Posterior Electrodes as Assessed Using EEG Analysis	Baseline up to Week 6
Cognition as Assessed by the Children's Memory Scale (CMS) Subtests Score	Baseline up to Week 6

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With AEs	Baseline up to Week 26
Percentage of Participants With Epileptiform Abnormalities as Assessed Using EEG Analysis	Baseline up to Week 26
Percentage of Participants by Suicidality Classification as Assessed Using an Adapted Form of the C-CASA	Baseline up to Week 26
ADAMS Score	Baseline up to Week 26
Hyperactivity and Impulsivity as Assessed by the Short Version of Conners-3 Score	Baseline up to Week 26
Sleep Disturbances as Assessed by the CSHQ Score	Baseline up to Week 26
Gamma Power at Posterior Electrodes as Assessed Using EEG Analysis	Baseline up to Week 26
Theta Power at Posterior Electrodes as Assessed Using EEG Analysis	Baseline up to Week 26
Cognition as Assessed by the CMS Subtests Score	Baseline up to Week 26
Adaptive Behavior as Assessed by the Vineland Adaptive Behavior Scales-II (VABS-II) Score	Baseline up to Week 26
Clinical Global Impression-Improvement (CGI-I) Scale Score	Baseline up to Week 26
Daily Functional Memory as Assessed by the Observer Memory Questionnaire-Parent Form (OMQ-PF) Score	Baseline up to Week 26
Intellectual Quotient (IQ) as Assessed by the Leiter 3	Baseline up to Week 26
Plasma Concentration of RO5186582	Predose (2 predose samples separated by at least 1 hour) at Weeks 2 and 6; and predose or postdose (as convenient) during Weeks 10, 17, and 26

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2015
• Primary Completion (Actual): August 3, 2016
• Study Completion (Actual): August 3, 2016

Study Registration Dates

• First Submitted: June 16, 2015
• First Submitted That Met QC Criteria: June 24, 2015
• First Posted (Estimate): June 30, 2015

Study Record Updates

• Last Update Posted (Actual): July 6, 2017
• Last Update Submitted That Met QC Criteria: July 4, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Syndrome; Down Syndrome
• Other Study ID Numbers: WP28760