Clinical Trial to Evaluate the Efficacy, Safety, and Tolerability of RO7239361 in Ambulatory Boys With Duchenne Muscular Dystrophy

A Randomized, Double Blind, Placebo-Controlled, Study to Assess the Efficacy, Safety, and Tolerability of RO7239361 in Ambulatory Boys With Duchenne Muscular Dystrophy

This is a multi-center, randomized, double-blind, placebo-controlled study to assess the efficacy, safety and tolerability of two different weekly doses of RO7239361 in ambulatory boys with Duchenne Muscular Dystrophy (DMD).

Study Overview

• Status: Completed
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: RO7239361; Drug: Placebo for RO7239361

• Study Type: Interventional
• Enrollment (Actual): 166
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1204AAD
    • Instituto Centenario
• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Children's Hospital Westmead; Paediatrics & Child Health
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Lady Cilento Children's Hospital; Neurosciences Department
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital
• Belgium
  • Gent, Belgium, 9000
    • UZ Gent
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre; Children's Hospital; Pediatrics
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
• France
  • Lyon, France, 69004
    • Hospices Civils de Lyon
  • Nantes, France, 44093
    • Hotel Dieu; Service Pharmacie Essais Cliniques
  • Paris Cedex 12, France, 75571
    • Hopital Armand Trousseau; centre reference Maladies Neuro-musculaires Est parisien Neuropediatrie
  • Strasbourg, France, 67091
    • Hopitaux Universitaires de Strasbourg
• Germany
  • Essen, Germany, 45122
    • Universitatsklinikum Essen; Innere Klinik
• Italy
  • Emilia-Romagna
    • Milano, Emilia-Romagna, Italy, 20162
      • Fondazione Serena Onlus - Centro Clinico Nemo
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Fondazione Policlinico Universitario A Gemelli; Servizio di Farmacia
  • Sicilia
    • Messina, Sicilia, Italy, 98125
      • Az. Osp. Universitaria Pol. G. Martino; Dip. Neuroscienze, Scienze Psichiatriche e Anest.
• Japan
  • Hyogo, Japan, 663-8501
    • Hyogo College of Medicine Hospital
  • Miyagi, Japan, 989-3126
    • Miyagi Children's Hospital
  • Nagano, Japan, 390-8621
    • Shinshu University Hospital
  • Osaka, Japan, 560-8552
    • National Hospital Organization Osaka Toneyama Medical Center
  • Tokyo, Japan, 187-8551
    • National Center of Neurology and Psychiatry
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Leids Universitair Medisch Centrum
  • Nijmegen, Netherlands, 6525 EX
    • Radboud University Nijmegen Medical Centre; Ophthalmology
• Spain
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia; Servicio de Farmacia
  • Barcelona
    • Esplugues De Llobregas, Barcelona, Spain, 08950
      • Hospital Sant Joan de Déu
• Sweden
  • Goeteborg, Sweden, 41685
    • Drottning Silvias Barn- och ungdomssjukhus; Kliniken för barnmedicin
• United Kingdom
  • Liverpool, United Kingdom, L12 2AP
    • Alder Hey Children s Hospital; Department of Pediatrics
  • London, United Kingdom, WC1N 1EH
    • UCL Institute of Child Health & Great Ormond Street Hospital for Children
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85028
      • Neuromuscular Research Center
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School of Medicine ; Pulmonary & Critical Care
  • Florida
    • Gainesville, Florida, United States, 32607
      • University of Florida
    • Orlando, Florida, United States, 32827
      • Nemours Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Rare Disease Research, LLC
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center - PPDS
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Kennedy Krieger Institute
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Childrens Medical Center; Department of Neurology
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis Children's Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89145
      • Las Vegas Clinic
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Childrens Hospital Medical Center;Investigational Pharmacy
    • Columbus, Ohio, United States, 43205
      • Nationwide Childrens Hospital; Research Institute at Nationwide Childrens Hospital
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Diagnosed with DMD by confirmed medical history and genetic testing
• Able to walk without assistance
• Minimum North Star Ambulatory Assessment score of 15 at screening
• Able to walk up 4 stairs in 8 seconds or less
• Weigh at least 15 kg (33 lbs)
• Taking corticosteroids for DMD

Exclusion Criteria:

• Any behavior or mental issue that will affect the ability to complete the required study procedures
• Previously or currently taking medications like androgens or human growth hormone
• Use of a ventilator during the day
• Unable to have blood samples collected or receive an injection under the skin
• Concomitant or previous participation at any time in a gene therapy study

Other protocol defined Inclusion/Exclusion Criteria could apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RO7239361 Low Dose; Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Drug: RO7239361; Take RO7239361 subcutaneously on specified days over a 48 week blinded period
Experimental: RO7239361 High Dose; Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Drug: RO7239361; Take RO7239361 subcutaneously on specified days over a 48 week blinded period
Placebo Comparator: Placebo; Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Drug: Placebo for RO7239361; Take placebo subcutaneously on specified days over a 48 week blinded period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline for the North Star Ambulatory Assessment (NSAA) Total Score	The NSAA is a functional scale specifically designed for ambulant boys with Duchenne muscular dystrophy (DMD) that can provide information about motor function. The NSAA is a 17-item test of standing, ability to transition from lying to sitting, sitting to standing, and other mobility assessments. Each of the 17 items is evaluated on an ordinal scale of 0-2: 0 = unable to achieve independently, 1 = modified method but achieves goal independent of physical assistance from another, or 2 = normal with no obvious modification of activity. Total score range is 0 to 34. Higher scores reflect better performance.	Baseline
Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 48	The NSAA is a functional scale specifically designed for ambulant boys with Duchenne muscular dystrophy (DMD) that can provide information about motor function. The NSAA is a 17-item test of standing, ability to transition from lying to sitting, sitting to standing, and other mobility assessments. Each of the 17 items is evaluated on an ordinal scale of 0-2: 0 = unable to achieve independently, 1 = modified method but achieves goal independent of physical assistance from another, or 2 = normal with no obvious modification of activity. Total score range is 0 to 34. Higher scores reflect better performance. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).	Baseline, Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline Time for 4 Stair Climb	The time to complete the 4 stair climb was measured at baseline.	Baseline
Change From Baseline at Week 48 in 4 Stair Climb Velocity (4SCV)	4SCV was calculated as the ratio of the number of stairs climbed (4) divided by the number of seconds taken to complete the 4-stair climb. The results were converted into velocity (distance/time). A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).	Baseline, Week 48
Baseline for the Time to Stand From Supine	The time required for a participant to stand from supine position. A longer time reflects a worse outcome.	Baseline
Change From Baseline at Week 48 in Stand From Supine Velocity	The time required for a participant to stand from supine position. A longer time reflects a worse outcome. A negative change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).	Baseline, Week 48
Baseline Time for 10 Meter Walk/Run	The time required for a participant to run or walk a distance of 10 meters as quickly as possible. A longer time reflects a worse outcome.	Baseline
Change From Baseline at Week 48 in 10 M Walk/Run Velocity	The time required for a participant to run or walk a distance of 10 meters as quickly as possible calculated as velocity (distance/time). A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).	Baseline, Week 48
Baseline for the Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale	The PODCI is designed to be completed by the parent/guardian of a child who has knowledge of the child's conditions. The Transfer and Basic Mobility scale is one of the subscales of the PODCI. The results are standardized into a scale of 0-100 with a higher score reflecting better performance.	Baseline
Change From Baseline at Week 48 in Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale	The PODCI is designed to be completed by the parent/guardian of a child who has knowledge of the child's conditions. The Transfer and Basic Mobility scale is one of the subscales of the PODCI. The results are standardized into a scale of 0-100 with a higher score reflecting better performance. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).	Baseline, Week 48
Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength	Proximal lower extremity flexor (knee extension and knee flexion) strength was measured using manual myometry. A higher score reflects a better outcome. A positive change from baseline indicates an improvement.	Baseline, Week 48
Baseline for the 6 Minute Walk Distance (6MWD)	The 6MWD measured the distance a participant was able to traverse while walking for 6 minutes. A longer distance reflects a better outcome.	Baseline
Change From Baseline at Week 48 in 6 Minute Walk Distance (6MWD)	The 6MWD measured the distance a participant was able to traverse while walking for 6 minutes. A longer distance reflects a better outcome. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).	Baseline, Week 48
Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48	The CGI-C was used to assess the participant's overall condition on a 7-point scale, using the status markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse" at Week 48 as compared to baseline.	Baseline, Week 48
Change From Baseline at Week 48 in 95th Percentile Stride Velocity	Stride velocity was recorded with the ActiMyo device in a subset of the overall study population. The ActiMyo device measures the daily movement and activity levels of the participant. The device consists of two sensors worn on each ankle. A higher velocity reflects a better outcome. A positive change from baseline indicates an improvement.	Baseline, Week 48
Number of Participants With Adverse Events (AEs)	An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	During DB period (48 weeks) and Whole study (up to approximately 34 months)
Number of Participants With AEs Leading to Discontinuation	An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Reported here is the number of participants with AEs that led to study discontinuation.	During DB period (48 weeks) and Whole study (up to approximately 34 months)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

Helpful Links

• FDA Safety Alerts and Recalls
• Provides information about the Roche clinical trial NCT03039686 and molecule being investigated in Duchenne

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2017
• Primary Completion (Actual): April 28, 2020
• Study Completion (Actual): April 28, 2020

Study Registration Dates

• First Submitted: January 27, 2017
• First Submitted That Met QC Criteria: January 31, 2017
• First Posted (Estimate): February 1, 2017

Study Record Updates

• Last Update Posted (Actual): December 21, 2020
• Last Update Submitted That Met QC Criteria: November 25, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: DMD; muscular dystrophy; Duchenne's Muscular Dystrophy
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: CN001-016; 2016-001654-18 (EudraCT Number); WN40227 (Other Identifier: Hoffman-La Roche)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No