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

NCT02024789 | Completed Phase 2

• 2 other identifiers: BP278322013-001263-23
• Study Type: interventional
• Target: 173
• Locations: 10 countries
• Sites: 37

Brief Summary

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.

Conditions

Down Syndrome

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• 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

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

RG1662 120 mg bid

EXPERIMENTAL

Drug: RG1662

RG1662 240 mg bid

EXPERIMENTAL

Drug: RG1662

Interventions

Placebo DRUG

Orally twice daily, 26 weeks

Placebo

RG1662 DRUG

120 mg (80 mg for subjects 12 and 13 years of age) orally twice daily, 26 weeks

RG1662 120 mg bid

Eligibility Criteria

• Age: 12 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (37)

Univ of CA San Diego; Neurosciences Comp.Alzheimer's

La Jolla, California, 92037, United States

Location

University of California DAVIS Medical Center; M.I.N.D. Institute, Section of Developmental Behavior

Sacramento, California, 95817, United States

Location

Emory University School of Medicine; Department of Human Genetics & Pediatrics

Decatur, Georgia, 30033, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Johns Hopkins Hospital.

Baltimore, Maryland, 21287, United States

Location

Massachusette General Hospital; Medical Genetics

Boston, Massachusetts, 02114, United States

Location

Duke Clin Rsch Institute

Durham, North Carolina, 27710, United States

Location

University of Utah School of Medicine; Department of Pediatrics

Salt Lake City, Utah, 84112, United States

Location

University of Wisconsin Madison, Waisman Center

Madison, Wisconsin, 53705, United States

Location

FLENI

CABA, C1428AQK, Argentina

Location

Instituto Neurologia Bs As

Ciudad Autonoma de Bs As, 1426, Argentina

Location

True North Clinical Research Kentville

Kentville, Nova Scotia, B4N 4K9, Canada

Location

Groupement Hospitalier Est-Hopital Femme Mere enfant/Hospice civils de lyon

Bron, 69003, France

Location

CHU de Montpellier Hopital Arnaud de Villeneuve; de Génétique

Montpellier, 34295, France

Location

Institut Jérôme Lejeune; Neuropsychology

Paris, 75015, France

Location

CHU de Saint Etienne; Service de Génétique

Saint-Etienne, 42055, France

Location

Ospedale Pediatrico Bambino Gesù

Rome, Lazio, 00165, Italy

Location

Policlinico Universitario "Agostino Gemelli";Dip. Tutela Salute Donna Bambino Adolescente

Rome, Lazio, 00168, Italy

Location

Ospedale Microcitemico; Clinica Pediatrica

Cagliari, Sardinia, 09121, Italy

Location

Hospital Dr. Angel Leaño; Pediatria

Guadalajara, Jalisco, 45200, Mexico

Location

Clínica Para la Atención del Neurodesarrollo

Aguascalientes, 20030, Mexico

Location

Hospital Universitario Dr. Jose Eleuterio Gonzalez; Pediatria

Monterrey, 64460, Mexico

Location

Hospital Médica Tec 100

Querétaro, 76000, Mexico

Location

Auckland Clinical Studies

Auckland, 1142, New Zealand

Location

University of Otago; Psychological Medicine Department

Dunedin, 9016, New Zealand

Location

Wellington Hospital Research Office

Wellington, 6021, New Zealand

Location

KK Women's and Children's Hospital; Department of Neonatology

Singapore, 229899, Singapore

Location

UVaMID Hospital Santa Caterina;; Servicio de Neurología

Salt, Girona, 17090, Spain

Location

Complejo Hospitalario Universitario de Santiago (CHUS); Area Asistencial Integrada de Pediatría

Santiago de Compostela, La Coruña, 15706, Spain

Location

IMIM, Human Pharmacology and Clinical Neurosciences,

Barcelona, 08009, Spain

Location

Hospital Universitario de la Princesa; Medicina Interna

Madrid, 28006, Spain

Location

Hospital Infantil Universitario Niño Jesus; Pediatria Social

Madrid, 28009, Spain

Location

Fundación Síndrome de Down; Fundación Síndrome de Down

Madrid, 28016, Spain

Location

Blackpool Teaching Hospitals NHS Foundation Trust; Child Development and Family Support Centre

Blackpool, United Kingdom

Location

Mental Health of Learning Disability, Kent & Medway NHS and Social Care Partnership Trust

Dartford, Kent, DA2 6PB, United Kingdom

Location

Doncaster and Bassetlaw Hospitals NHS Foundation Trust; Doncaster Royal Infirmary

Doncaster, DN2 5LT, United Kingdom

Location

Cornwall Partnership NHS Foundation Trust

Redruth, TR15 2SP, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35123401 DERIVED

MeSH Terms

Conditions

Down Syndrome

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2013
• First Posted: December 31, 2013
• Study Start: May 5, 2014
• Primary Completion: May 4, 2016
• Study Completion: May 4, 2016
• Last Updated: October 25, 2017

Record last verified: 2017-10

Locations

ES (6); NZ (3); FR (4); IT (3); SG (1); ME (4); GB (4); US (9); AR (2); CA (1)