A Study of RO6885247 in Adult and Pediatric Patients With Spinal Muscular Atrophy (MOONFISH)

Muscular Atrophy, Spinal Clinical Trial

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).

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02240355
• Other study ID #: BP29420
• Secondary ID: 2014-002246-41
• Status: Terminated
• Phase: Phase 1
• First received: September 11, 2014
• Last updated: December 20, 2016
• Start date: November 2014
• Est. completion date: July 2015

Study information

• Verified date: December 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal

Intervention

Drug:
• RO6885247
oral solution
• placebo
oral solution

Locations

Country	Name	City	State
France	Ch Pitie Salpetriere; Institut de Myologie	Paris
Italy	Fondazione IRCCS Istituto Neurologico "Carlo Besta"; UO di Neurologia dello Sviluppo	Milano	Lombardia
Italy	Policlinico Agostino Gemelli; Dipartimento di Neuropsichiatria Infantile	Roma	Lazio
Netherlands	UMC Utrecht; Polkliniek Neuromusculaire ziekten	Utrecht
Sweden	Drottning Silvias Barn- och ungdomssjukhus; Kliniken för barnmedicin	Goeteborg
Switzerland	Universitäts-Kinderspitalbeider Basel_Abteilung für Neuro- und Entwicklungspädiatrie	Basel
Turkey	Hacettepe University, School of Medicine; Pediatrics Department; Pediatrics Child Neurology Unit	Ankara
United Kingdom	UCL; GAP Unit, Institute of Child Health, UCL	London
United Kingdom	MRC Neuromuscular Centre - Institute of Genetic Medicine	Newcastle upon Tyne

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Canada,  France,  Italy,  Netherlands,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Incidence of adverse events (AEs)		Up to 20 weeks	No
Secondary	Pharmacokinetics: RO6885247 plasma concentrations		Up to 16 weeks	No
Secondary	Pharmacokinetics: RO6885247 exposure, area under the concentration-time curve (AUC-tau, over the 24-hour dosing interval)		Up to 12 weeks	No
Secondary	Pharmacodynamics: SMN protein levels in blood		Up to 20 weeks	No
Secondary	Effect of RO6885247 on muscle electrophysiology, as assessed by Compound Muscle Action Potential (CMAP)		Up to 20 weeks	No
Secondary	Effect of RO6885247 on Electrical Impedance Myography		Up to 20 weeks	No
Secondary	Pharmacodynamics: In vivo splicing modification of SMN2 mRNA in blood		Up to 20 weeks	No