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

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)

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.

Study Overview

• Status: Completed
• Conditions: Down Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: RG1662; Drug: RG1662

• Study Type: Interventional
• Enrollment (Actual): 173
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Caba, Argentina, C1428AQK
    • FLENI
  • Ciudad Autonoma de Bs As, Argentina, 1426
    • Instituto Neurologia Bs As
• Canada
  • Nova Scotia
    • Kentville, Nova Scotia, Canada, B4N 4K9
      • True North Clinical Research Kentville
• France
  • Bron, France, 69003
    • Groupement Hospitalier Est-Hopital Femme Mere enfant/Hospice civils de lyon
  • Montpellier, France, 34295
    • CHU de Montpellier Hopital Arnaud de Villeneuve; de Génétique
  • Paris, France, 75015
    • Institut Jérôme Lejeune; Neuropsychology
  • St Etienne, France, 42055
    • CHU de Saint Etienne; Service de Génétique
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00165
      • Ospedale Pediatrico Bambino Gesù
    • Roma, Lazio, Italy, 00168
      • Policlinico Universitario "Agostino Gemelli";Dip. Tutela Salute Donna Bambino Adolescente
  • Sardegna
    • Cagliari, Sardegna, Italy, 09121
      • Ospedale Microcitemico; Clinica Pediatrica
• Mexico
  • Aguascalientes, Mexico, 20030
    • Clínica Para la Atención del Neurodesarrollo
  • Monterrey, Mexico, 64460
    • Hospital Universitario Dr. Jose Eleuterio Gonzalez; Pediatria
  • Queretaro, Mexico, 76000
    • Hospital Médica Tec 100
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 45200
      • Hospital Dr. Angel Leaño; Pediatria
• New Zealand
  • Auckland, New Zealand, 1142
    • Auckland Clinical Studies
  • Dunedin, New Zealand, 9016
    • University of Otago; Psychological Medicine Department
  • Wellington, New Zealand, 6021
    • Wellington Hospital Research Office
• Singapore
  • Singapore, Singapore, 229899
    • KK Women's and Children's Hospital; Department of Neonatology
• Spain
  • Barcelona, Spain, 08009
    • IMIM, Human Pharmacology and Clinical Neurosciences,
  • Madrid, Spain, 28009
    • Hospital Infantil Universitario Niño Jesus; Pediatria Social
  • Madrid, Spain, 28006
    • Hospital Universitario de la Princesa; Medicina Interna
  • Madrid, Spain, 28016
    • Fundación Síndrome de Down; Fundación Síndrome de Down
  • Girona
    • Salt, Girona, Spain, 17090
      • UVaMID Hospital Santa Caterina;; Servicio de Neurología
  • La Coruña
    • Santiago de Compostela, La Coruña, Spain, 15706
      • Complejo Hospitalario Universitario de Santiago (CHUS); Area Asistencial Integrada de Pediatría
• United Kingdom
  • Blackpool, United Kingdom
    • Blackpool Teaching Hospitals NHS Foundation Trust; Child Development and Family Support Centre
  • Dartford, Kent, United Kingdom, DA2 6PB
    • Mental Health of Learning Disability, Kent & Medway NHS and Social Care Partnership Trust
  • Doncaster, United Kingdom, DN2 5LT
    • Doncaster and Bassetlaw Hospitals NHS Foundation Trust; Doncaster Royal Infirmary
  • Redruth, United Kingdom, TR15 2SP
    • Cornwall Partnership NHS Foundation Trust
• United States
  • California
    • La Jolla, California, United States, 92037
      • Univ of CA San Diego; Neurosciences Comp.Alzheimer's
    • Sacramento, California, United States, 95817
      • University of California DAVIS Medical Center; M.I.N.D. Institute, Section of Developmental Behavior
  • 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
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital.
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusette General Hospital; Medical Genetics
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Clin Rsch Institute
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah School of Medicine; Department of Pediatrics
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin Madison, Waisman Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 30 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Orally twice daily, 26 weeks
EXPERIMENTAL: RG1662 120 mg bid	Drug: RG1662; 120 mg (80 mg for subjects 12 and 13 years of age) orally twice daily, 26 weeks; Drug: RG1662; 240 mg (160 mg for subjects 12 and 13 years of age) orally twice daily, 26 weeks
EXPERIMENTAL: RG1662 240 mg bid	Drug: RG1662; 120 mg (80 mg for subjects 12 and 13 years of age) orally twice daily, 26 weeks; Drug: RG1662; 240 mg (160 mg for subjects 12 and 13 years of age) orally twice daily, 26 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Goeldner C, Kishnani PS, Skotko BG, Casero JL, Hipp JF, Derks M, Hernandez MC, Khwaja O, Lennon-Chrimes S, Noeldeke J, Pellicer S, Squassante L, Visootsak J, Wandel C, Fontoura P, d'Ardhuy XL; Clematis Study Group. A randomized, double-blind, placebo-controlled phase II trial to explore the effects of a GABAA-alpha5 NAM (basmisanil) on intellectual disability associated with Down syndrome. J Neurodev Disord. 2022 Feb 5;14(1):10. doi: 10.1186/s11689-022-09418-0.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 5, 2014
• Primary Completion (ACTUAL): May 4, 2016
• Study Completion (ACTUAL): May 4, 2016

Study Registration Dates

• First Submitted: December 27, 2013
• First Submitted That Met QC Criteria: December 27, 2013
• First Posted (ESTIMATE): December 31, 2013

Study Record Updates

• Last Update Posted (ACTUAL): October 25, 2017
• Last Update Submitted That Met QC Criteria: October 24, 2017
• Last Verified: October 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: BP27832; 2013-001263-23 (EUDRACT_NUMBER)