Down Syndrome MedDRA version: 17.0 Level: PT Classification code 10044688 Term: Trisomy 21 System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: GABAA a5 receptor negative allosteric modulator
Product Code: RO5186582/F07
Pharmaceutical Form: Tablet
INN or Proposed INN: GABAA a5 receptor negative allosteric modulator
Current Spo
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Individuals aged 12-30 years of age inclusive. 2. Clinical diagnosis of Down syndrome (trisomy 21) confirmed by chromosomal analysis (karyotyping). Subjects may have standard trisomy 21, Robertsonian translocation, isochromosome 21 (so called 21q21q Robertsonian) translocation), Down syndrome with reciprocal translocation or mosaicism. 3. Males, or nonpregnant, nonlactating females. For females of childbearing potential, strict contraceptive prevention is required: continuation of hormonal contraception, or intra uterine device. True abstinence is acceptable provided that participants are under the supervision of a caregiver attesting that participants are not sexually active and the results of pregnancy tests are negative before onset of treatment. 4. Body-mass Index (BMI) 18-42 and 15-32 kg/m2 inclusive for adults and adolescents respectively 5. Ability to complete the Clinical Evaluation of Language Fundamentals (CELF)-preschool 2 word classes task (i.e., = 7 for adults or = 4 for adolescents in the expressive raw score). Are the trial subjects under 18? yes Number of subjects for this age range: 90 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects with a current Diagnostic and Statistical Manual of Mental Disorders (DSM 5) diagnosis of any primary psychiatric diagnosis (including autism spectrum disorder or major depressive disorder). Diagnoses that are secondary, such as intellectual disability, attention deficit hyperactivity disorder, depression and conduct disorder are allowed as long as they are considered to not interfere with study conduct and the subject is on stable treatment for 3 months preceding enrollment. 2. Subjects with a history of infantile spasms, of West syndrome, Lennox-Gastaut syndrome, Early Infantile Epileptic Encephalopathy or any treatment-refractory epilepsy associated with cognitive or developmental regression, of severe head trauma or CNS infections (e.g. meningitis). 3. Subjects with a known or suspected clinical seizure event of any type within 24 months prior to screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is as follows: • To evaluate the efficacy of 26 weeks of treatment with RO5186582 on a composite endpoint derived from clinically meaningful responses in working memory and on the level of independent functioning/adaptive behavior or global improvement as compared to placebo.;Primary end point(s): •Cognition as assessed by the Repeatable Battery for the Assessment of •Neuropsychological Status (RBANS) sub-tests •Clinical global impression as assessed by Clinician Rated Global Improvement (CGI-I) scale;Timepoint(s) of evaluation of this end point: • Base Line (except for CGI-I) 12 weeks and 26 Weeks (see protocol for details);Secondary Objective: Safety Objective: • Evaluate the tolerability and safety of 26 weeks treatment of RO5186582 and 4-6 weeks after the end of the treatment period Efficacy Objectives: • Evaluate the effect of 26 weeks treatment of RO5186582 compared to placebo on working memory • Evaluate the effect of 26 weeks treatment of RO5186582 compared to placebo on the level of independent functioning and adaptive behavior • Assess the effect of 26 weeks treatment of RO5186582 compared to placebo on global clinical condition • Evaluate the effect of 26 weeks treatment of RO518652 compared to placebo on executive function • Evaluate the effect of 26 weeks treatment of RO518652 compared to placebo on language function • Evaluate the effect of 26 weeks treatment of RO518652 compared to placebo on everyday memory function • Evaluate the effect of 26 weeks treatment of RO518652 compared to placebo on subject’s cognition and health-related quality of life as reported by the parents | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Everyday working memory as assessed by the Rivermead Behavioral Memory Test for Children (RBMT-C) sub-tests • Executive function as assessed by the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) • Daily functional memory as assessed by the Observer Memory Questionnaire-Parent Form (OMQ-PF) • Language function as assessed by the Clinical Evaluation of Language Fundamentals (CELF-4) • Health-related quality of life as assessed by the Pediatric Quality of Life (PedsQL) Generic Core Module v4.0 • Cognition as assessed by the PedsQL Cognitive Functioning Scale;Timepoint(s) of evaluation of this end point: • 12 weeks and 26 Weeks | — |
Countries
Argentina, Canada, France, Germany, Italy, Mexico, New Zealand, Singapore, Spain, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd.
Outcome results
None listed