A Study of RG1662 in Adults and Adolescents With Down Syndrome (CLEMATIS)

Study Overview
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Brief Summary
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This multi-center, randomized, double-blind, 3-arm, parallel-group, placebo-controlled study will evaluate the efficacy and safety of RG1662 in adults and adolescents with Down syndrome. Subjects will be randomized to receive RG1662 either at low or high dose or placebo orally twice daily for 26 weeks.

Official Title
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A MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 2 STUDY OF THE EFFICACY, SAFETY AND TOLERABILITY OF RG1662 IN ADULTS AND ADOLESCENTS WITH DOWN SYNDROME (CLEMATIS)

Conditions
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Down Syndrome

Intervention / Treatment
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* Drug: Placebo
* Drug: RG1662
* Drug: RG1662


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals aged 12-30 years of age inclusive Clinical diagnosis of Down syndrome (trisomy 21) confirmed by chromosomal analysis (karyotyping) Males, or non-pregnant, non-lactating females. For females of childbearing potential, strict contraceptive prevention is required. Body-mass Index (BMI) 18-42 and 15-30 kg/m2 inclusive for adults and adolescents respectively Ability to complete the Clinical Evaluation of Language Fundamentals (CELF)-preschool 2 word classes task Subjects must have a parent, or other reliable caregiver who agrees to accompany the subject to all clinic visits, provide information about the subject as required by the protocol, and ensure compliance with the medication schedule Study participants must have sufficient language, vision and hearing to participate in study evaluations, as judged clinically by investigator Exclusion Criteria: Subjects with a current DSM 5 diagnosis of any primary psychiatric diagnosis (including ASD or MDD) 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) Subjects with a known or suspected clinical seizure event of any type within 24 months prior to screening Clinically relevant ECG abnormalities at screening or baseline; QTcF above 450 ms; personal or family history (first degree relatives) of congenital long QT syndrome Inadequate renal or hepatic function

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Orally twice daily, 26 weeks<br>|
| Experimental: RG1662 120 mg bid<br> | Drug: RG1662<br>* 120 mg (80 mg for subjects 12 and 13 years of age) orally twice daily, 26 weeks<br>|
| Experimental: RG1662 240 mg bid<br> | Drug: RG1662<br>* 240 mg (160 mg for subjects 12 and 13 years of age) orally twice daily, 26 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognition as assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) sub-tests |  | 26 weeks | 
| Adaptive behavior as assessed by the Vineland Adaptive Behavior Scales-II (VABS-II) standard scores |  | 26 weeks | 
| Clinical global impression as assessed by Clinician Rated Global Improvement (CGI-I) scale |  | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of abnormal ECG changes |  | 26 weeks | 
| Abnormal ECG changes in adolescents as compared to baseline |  | from baseline to Week 26 | 
| Safety: Incidence of adverse events |  | approximately 32 weeks | 
| Incidence of abnormal blood pressure |  | 26 weeks | 
| RG1662 plasma concentrations |  | 26 weeks |