Clinical trial NCT02024789: A Study of RG1662 in Adults and Adolescents With Down Syndrome (CLEMATIS)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Down Syndrome
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-12-31
Enrollment: 173
Sex: ALL
Minimum age (years): 12
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Cognition as assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) sub-tests
timeFrame: 26 weeks
measure: Adaptive behavior as assessed by the Vineland Adaptive Behavior Scales-II (VABS-II) standard scores
timeFrame: 26 weeks
measure: Clinical global impression as assessed by Clinician Rated Global Improvement (CGI-I) scale
timeFrame: 26 weeks
Secondary outcomes:
measure: Incidence of abnormal ECG changes
timeFrame: 26 weeks
measure: Abnormal ECG changes in adolescents as compared to baseline
timeFrame: from baseline to Week 26
measure: Safety: Incidence of adverse events
timeFrame: approximately 32 weeks
measure: Incidence of abnormal blood pressure
timeFrame: 26 weeks
measure: RG1662 plasma concentrations
timeFrame: 26 weeks
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Univ of CA San Diego; Neurosciences Comp.Alzheimer's
state: California
city: Sacramento
country: United States
facility: University of California DAVIS Medical Center; M.I.N.D. Institute, Section of Developmental Behavior
state: California
city: Decatur
country: United States
facility: Emory University School of Medicine; Department of Human Genetics & Pediatrics
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Hospital.
state: Maryland
city: Boston
country: United States
facility: Massachusette General Hospital; Medical Genetics
state: Massachusetts
city: Durham
country: United States
facility: Duke Clin Rsch Institute
state: North Carolina
city: Salt Lake City
country: United States
facility: University of Utah School of Medicine; Department of Pediatrics
state: Utah
city: Madison
country: United States
facility: University of Wisconsin Madison, Waisman Center
state: Wisconsin
city: Caba
country: Argentina
facility: FLENI
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Instituto Neurologia Bs As
city: Kentville
country: Canada
facility: True North Clinical Research Kentville
state: Nova Scotia
city: Bron
country: France
facility: Groupement Hospitalier Est-Hopital Femme Mere enfant/Hospice civils de lyon
city: Montpellier
country: France
facility: CHU de Montpellier Hopital Arnaud de Villeneuve; de Génétique
city: Paris
country: France
facility: Institut Jérôme Lejeune; Neuropsychology
city: St Etienne
country: France
facility: CHU de Saint Etienne; Service de Génétique
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù
state: Lazio
city: Roma
country: Italy
facility: Policlinico Universitario "Agostino Gemelli";Dip. Tutela Salute Donna Bambino Adolescente
state: Lazio
city: Cagliari
country: Italy
facility: Ospedale Microcitemico; Clinica Pediatrica
state: Sardegna
city: Guadalajara
country: Mexico
facility: Hospital Dr. Angel Leaño; Pediatria
state: Jalisco
city: Aguascalientes
country: Mexico
facility: Clínica Para la Atención del Neurodesarrollo
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. Jose Eleuterio Gonzalez; Pediatria
city: Queretaro
country: Mexico
facility: Hospital Médica Tec 100
city: Auckland
country: New Zealand
facility: Auckland Clinical Studies
city: Dunedin
country: New Zealand
facility: University of Otago; Psychological Medicine Department
city: Wellington
country: New Zealand
facility: Wellington Hospital Research Office
city: Singapore
country: Singapore
facility: KK Women's and Children's Hospital; Department of Neonatology
city: Salt
country: Spain
facility: UVaMID Hospital Santa Caterina;; Servicio de Neurología
state: Girona
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS); Area Asistencial Integrada de Pediatría
state: La Coruña
city: Barcelona
country: Spain
facility: IMIM, Human Pharmacology and Clinical Neurosciences,
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa; Medicina Interna
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesus; Pediatria Social
city: Madrid
country: Spain
facility: Fundación Síndrome de Down; Fundación Síndrome de Down
city: Blackpool
country: United Kingdom
facility: Blackpool Teaching Hospitals NHS Foundation Trust; Child Development and Family Support Centre
city: Dartford, Kent
country: United Kingdom
facility: Mental Health of Learning Disability, Kent & Medway NHS and Social Care Partnership Trust
city: Doncaster
country: United Kingdom
facility: Doncaster and Bassetlaw Hospitals NHS Foundation Trust; Doncaster Royal Infirmary
city: Redruth
country: United Kingdom
facility: Cornwall Partnership NHS Foundation Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.