Clinical trial NCT02240355: A Study of RO6885247 in Adult and Pediatric Patients With Spinal Muscular Atrophy (MOONFISH)
Official title: A Multicenter, Randomized, Double Blind, Placebo Controlled, Multiple Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO6885247 Following 12 Weeks of Treatment in Adult and Pediatric Patients With Spinal Muscular Atrophy (MOONFISH).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Muscular Atrophy, Spinal
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-09-15
Enrollment: 9
Sex: ALL
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This multicenter, randomized, double-blind, 12-week, placebo-controlled multiple dose study will investigate the safety and tolerability of RO6885247 in adult and pediatric patients with spinal muscular atrophy (SMA).


Eligibility criteria: Inclusion Criteria:

* Males and females, aged 2 to 55 years inclusive or below 7 months inclusive
* Confirmed diagnosis of 5q-autosomal recessive SMA (Types 1 to 3), for patients aged 7 months or below clinical symptoms attributable to type 1 SMA and 2 SMN2 copies
* Able and willing to provide informed consent and to comply with the study protocol. Alternatively, a legally authorized representative must be able to consent for the patient and assent must be given by the subject wherever possible.
* Female patients of childbearing potential and male patients with a female partner of childbearing potential must agree with the required contraceptive methods as defined per protocol.
* For patients aged 7 months or below, Gestational age of 37 to 42 weeks and not considered small for gestational age at birth

Exclusion Criteria:

* Concomitant or previous participation in any investigational drug or device study within 90 days prior to screening
* Concomitant or previous participation in a SMN2-targeting antisense oligonucleotide study within 12 months prior to screening
* Concomitant or previous participation at any time in a gene therapy study
* For patients aged 2-55 years, hospitalization for pulmonary event within the last 2 months or planned at the time of screening
* Surgery for scoliosis in the last 6 months from screening or planned within 6 months from screening
* Unstable gastrointestinal, renal, hepatic, endocrine or cardiovascular system disease
* Clinically relevant ECG abnormalities at screening or baseline; personal or family history (first degree relatives) of congenital long QT syndrome
* Clinically significant abnormalities in laboratory test results at screening
* Any concomitant disease or condition that could interfere with the conduct of the study, or pose an unacceptable risk to the subject in this study
* Use of prohibited medications as per protocol within 90 days prior to randomization. Patients who are on inhaled corticosteroids, administered either through a nebulizer or an inhaler, are allowed.
* Recently initiated treatment (within \<6 months prior to randomization) with oral salbutamol or another beta2-adrenergic agonist taken orally is not allowed. Patients who have been on oral salbutamol (or another beta2-adrenergic agonist) for at least 6 months before randomization are allowed. Use of inhaled beta2-adrenergic agonists is allowed.
* For patients aged 7 months or below, patients requiring invasive ventilation or tracheostomy, presence of non-SMA related morbidities

Primary outcomes:
measure: Safety: Incidence of adverse events (AEs)
timeFrame: Up to 20 weeks
Secondary outcomes:
measure: Pharmacokinetics: RO6885247 plasma concentrations
timeFrame: Up to 16 weeks
measure: Pharmacokinetics: RO6885247 exposure, area under the concentration-time curve (AUC-tau, over the 24-hour dosing interval)
timeFrame: Up to 12 weeks
measure: Pharmacodynamics: SMN protein levels in blood
timeFrame: Up to 20 weeks
measure: Effect of RO6885247 on muscle electrophysiology, as assessed by Compound Muscle Action Potential (CMAP)
timeFrame: Up to 20 weeks
measure: Effect of RO6885247 on Electrical Impedance Myography
timeFrame: Up to 20 weeks
measure: Pharmacodynamics: In vivo splicing modification of SMN2 mRNA in blood
timeFrame: Up to 20 weeks
Other outcomes:
Locations:
city: Stanford
country: United States
state: California
city: Orlando
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Boston
country: United States
state: Massachusetts
city: St. Louis
country: United States
state: Missouri
city: New York
country: United States
state: New York
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Paris
country: France
facility: Ch Pitie Salpetriere; Institut de Myologie
city: Paris
country: France
city: Roma
country: Italy
facility: Policlinico Agostino Gemelli; Dipartimento di Neuropsichiatria Infantile
state: Lazio
city: Roma
country: Italy
state: Lazio
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico "Carlo Besta"; UO di Neurologia dello Sviluppo
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Utrecht
country: Netherlands
facility: UMC Utrecht; Polkliniek Neuromusculaire ziekten
city: Utrecht
country: Netherlands
city: Goeteborg
country: Sweden
facility: Drottning Silvias Barn- och ungdomssjukhus; Kliniken för barnmedicin
city: Goeteborg
country: Sweden
city: Basel
country: Switzerland
facility: Universitäts-Kinderspitalbeider Basel_Abteilung für Neuro- und Entwicklungspädiatrie
city: Basel
country: Switzerland
city: Ankara
country: Turkey
facility: Hacettepe University, School of Medicine; Pediatrics Department; Pediatrics Child Neurology Unit
city: Ankara
country: Turkey
city: London
country: United Kingdom
facility: UCL; GAP Unit, Institute of Child Health, UCL
city: London
country: United Kingdom
city: Newcastle upon Tyne
country: United Kingdom
facility: MRC Neuromuscular Centre - Institute of Genetic Medicine
city: Newcastle upon Tyne
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: