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

December 20, 2016 updated by: Hoffmann-La Roche

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).

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).

Study Overview

Status

Terminated

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
    • Quebec
      • Montreal, Quebec, Canada
      • Paris, France, 75013
      • Paris, France, 75013
        • Ch Pitie Salpetriere; Institut de Myologie
    • Lazio
      • Roma, Lazio, Italy, 00168
      • Roma, Lazio, Italy, 00168
        • Policlinico Agostino Gemelli; Dipartimento di Neuropsichiatria Infantile
    • Lombardia
      • Milano, Lombardia, Italy, 20133
      • Milano, Lombardia, Italy, 20133
        • Fondazione IRCCS Istituto Neurologico "Carlo Besta"; UO di Neurologia dello Sviluppo
      • Utrecht, Netherlands, 3584 CX
      • Utrecht, Netherlands, 3584 CX
        • UMC Utrecht; Polkliniek Neuromusculaire ziekten
      • Goeteborg, Sweden, 41685
        • Drottning Silvias Barn- och ungdomssjukhus; Kliniken för barnmedicin
      • Goeteborg, Sweden, 41685
      • Basel, Switzerland, 4005
        • Universitäts-Kinderspitalbeider Basel_Abteilung für Neuro- und Entwicklungspädiatrie
      • Basel, Switzerland, 4005
      • Ankara, Turkey, 06100
      • Ankara, Turkey, 06100
        • Hacettepe University, School of Medicine; Pediatrics Department; Pediatrics Child Neurology Unit
      • London, United Kingdom, WC1N 1EH
        • UCL; GAP Unit, Institute of Child Health, UCL
      • London, United Kingdom, WC1N 1EH
      • Newcastle upon Tyne, United Kingdom, NE1 3BZ
        • MRC Neuromuscular Centre - Institute of Genetic Medicine
      • Newcastle upon Tyne, United Kingdom, NE1 3BZ
    • California
      • Stanford, California, United States, 94305
    • Florida
      • Orlando, Florida, United States, 32827
    • Illinois
      • Chicago, Illinois, United States, 60611-2605
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
    • Missouri
      • St. Louis, Missouri, United States, 63110
    • New York
      • New York, New York, United States, 10032

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 55 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Part 1
Up to 2 cohorts of patients, within each cohort patients will receive either RO6885247 or placebo once daily for 12 weeks
oral solution
oral solution
EXPERIMENTAL: Part 2
1 cohort of patients, within each cohort patients will receive either RO6885247 or placebo once daily for 12 weeks
oral solution
oral solution
EXPERIMENTAL: Part 3
1 cohort of patients, within each cohort patients will receive RO6885247 once daily for 12 weeks or 20 weeks
oral solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety: Incidence of adverse events (AEs)
Time Frame: Up to 20 weeks
Up to 20 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetics: RO6885247 plasma concentrations
Time Frame: Up to 16 weeks
Up to 16 weeks
Pharmacokinetics: RO6885247 exposure, area under the concentration-time curve (AUC-tau, over the 24-hour dosing interval)
Time Frame: Up to 12 weeks
Up to 12 weeks
Pharmacodynamics: SMN protein levels in blood
Time Frame: Up to 20 weeks
Up to 20 weeks
Effect of RO6885247 on muscle electrophysiology, as assessed by Compound Muscle Action Potential (CMAP)
Time Frame: Up to 20 weeks
Up to 20 weeks
Effect of RO6885247 on Electrical Impedance Myography
Time Frame: Up to 20 weeks
Up to 20 weeks
Pharmacodynamics: In vivo splicing modification of SMN2 mRNA in blood
Time Frame: Up to 20 weeks
Up to 20 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2014

Primary Completion (ACTUAL)

July 1, 2015

Study Completion (ACTUAL)

July 1, 2015

Study Registration Dates

First Submitted

September 11, 2014

First Submitted That Met QC Criteria

September 11, 2014

First Posted (ESTIMATE)

September 15, 2014

Study Record Updates

Last Update Posted (ESTIMATE)

December 22, 2016

Last Update Submitted That Met QC Criteria

December 20, 2016

Last Verified

December 1, 2016

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Muscular Atrophy, Spinal

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