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

• ClinicalTrials.gov Identifier: NCT03039686
• Recruitment Status: Completed
• First Posted: February 1, 2017
• Results First Posted: December 21, 2020
• Last Update Posted: December 21, 2020
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Duchenne Muscular Dystrophy	Drug: RO7239361; Drug: Placebo for RO7239361	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 166 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double Blind, Placebo-Controlled, Study to Assess the Efficacy, Safety, and Tolerability of RO7239361 in Ambulatory Boys With Duchenne Muscular Dystrophy
• Actual Study Start Date: July 6, 2017
• Actual Primary Completion Date: April 28, 2020
• Actual Study Completion Date: April 28, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Baseline for the North Star Ambulatory Assessment (NSAA) Total Score [ Time Frame: Baseline ]
   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.
2. Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 48 [ Time Frame: Baseline, 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).

Secondary Outcome Measures :

1. Baseline Time for 4 Stair Climb [ Time Frame: Baseline ]
   The time to complete the 4 stair climb was measured at baseline.
2. Change From Baseline at Week 48 in 4 Stair Climb Velocity (4SCV) [ Time Frame: Baseline, Week 48 ]
   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).
3. Baseline for the Time to Stand From Supine [ Time Frame: Baseline ]
   The time required for a participant to stand from supine position. A longer time reflects a worse outcome.
4. Change From Baseline at Week 48 in Stand From Supine Velocity [ Time Frame: Baseline, Week 48 ]
   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).
5. Baseline Time for 10 Meter Walk/Run [ Time Frame: Baseline ]
   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.
6. Change From Baseline at Week 48 in 10 M Walk/Run Velocity [ Time Frame: Baseline, Week 48 ]
   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).
7. Baseline for the Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale [ Time Frame: Baseline ]
   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.
8. Change From Baseline at Week 48 in Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale [ Time Frame: Baseline, Week 48 ]
   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).
9. Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength [ Time Frame: Baseline, Week 48 ]
   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.
10. Baseline for the 6 Minute Walk Distance (6MWD) [ Time Frame: Baseline ]
    The 6MWD measured the distance a participant was able to traverse while walking for 6 minutes. A longer distance reflects a better outcome.
11. Change From Baseline at Week 48 in 6 Minute Walk Distance (6MWD) [ Time Frame: Baseline, Week 48 ]
    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).
12. Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 [ Time Frame: Baseline, 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.
13. Change From Baseline at Week 48 in 95th Percentile Stride Velocity [ Time Frame: Baseline, Week 48 ]
    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.
14. Number of Participants With Adverse Events (AEs) [ Time Frame: During DB period (48 weeks) and Whole study (up to approximately 34 months) ]
    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.
15. Number of Participants With AEs Leading to Discontinuation [ Time Frame: During DB period (48 weeks) and Whole study (up to approximately 34 months) ]
    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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

Neuromuscular Research Center

Phoenix, Arizona, United States, 85028

United States, California

Stanford University

Palo Alto, California, United States, 94304

University of California Davis Medical Center

Sacramento, California, United States, 95817

United States, Connecticut

Yale University School of Medicine ; Pulmonary & Critical Care

New Haven, Connecticut, United States, 06510

United States, Florida

University of Florida

Gainesville, Florida, United States, 32607

Nemours Children's Hospital

Orlando, Florida, United States, 32827

United States, Georgia

Rare Disease Research, LLC

Atlanta, Georgia, United States, 30318

United States, Illinois

Rush University Medical Center - PPDS

Chicago, Illinois, United States, 60612

United States, Iowa

University of Iowa

Iowa City, Iowa, United States, 52242

United States, Kansas

University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

United States, Maryland

Kennedy Krieger Institute

Baltimore, Maryland, United States, 21205

United States, Massachusetts

University of Massachusetts Memorial Childrens Medical Center; Department of Neurology

Worcester, Massachusetts, United States, 01655

United States, Missouri

Saint Louis Children's Hospital

Saint Louis, Missouri, United States, 63110

United States, Nevada

Las Vegas Clinic

Las Vegas, Nevada, United States, 89145

United States, Ohio

Cincinnati Childrens Hospital Medical Center;Investigational Pharmacy

Cincinnati, Ohio, United States, 45229

Nationwide Childrens Hospital; Research Institute at Nationwide Childrens Hospital

Columbus, Ohio, United States, 43205

United States, Washington

Seattle Children's Hospital

Seattle, Washington, United States, 98105

Argentina

Instituto centenario

Buenos Aires, Argentina, C1204AAD

Australia, New South Wales

Children's Hospital Westmead; Paediatrics & Child Health

Westmead, New South Wales, Australia, 2145

Australia, Queensland

Lady Cilento Children's Hospital; Neurosciences Department

South Brisbane, Queensland, Australia, 4101

Australia, Victoria

Royal Children's Hospital

Parkville, Victoria, Australia, 3052

Belgium

UZ Gent

Gent, Belgium, 9000

Canada, Ontario

London Health Sciences Centre; Children's Hospital; Pediatrics

London, Ontario, Canada, N6A 5W9

Children'S Hospital of Eastern Ontario

Ottawa, Ontario, Canada, K1H 8L1

France

Hospices Civils de Lyon

Lyon, France, 69004

Hotel Dieu; Service Pharmacie Essais Cliniques

Nantes, France, 44093

Hopital Armand Trousseau; centre reference Maladies Neuro-musculaires Est parisien Neuropediatrie

Paris Cedex 12, France, 75571

Hopitaux Universitaires de Strasbourg

Strasbourg, France, 67091

Germany

Universitatsklinikum Essen; Innere Klinik

Essen, Germany, 45122

Italy

Fondazione Serena Onlus - CENTRO CLINICO NEMO

Milano, Emilia-Romagna, Italy, 20162

Fondazione Policlinico Universitario A Gemelli; Servizio di Farmacia

Rome, Lazio, Italy, 00168

Az. Osp. Universitaria Pol. G. Martino; Dip. Neuroscienze, Scienze Psichiatriche e Anest.

Messina, Sicilia, Italy, 98125

Japan

Hyogo College of Medicine Hospital

Hyogo, Japan, 663-8501

Miyagi Children's Hospital

Miyagi, Japan, 989-3126

Shinshu University Hospital

Nagano, Japan, 390-8621

National Hospital Organization Osaka Toneyama Medical Center

Osaka, Japan, 560-8552

National Center of Neurology and Psychiatry

Tokyo, Japan, 187-8551

Netherlands

Leids Universitair Medisch Centrum

Leiden, Netherlands, 2333 ZA

Radboud University Nijmegen Medical Centre; Ophthalmology

Nijmegen, Netherlands, 6525 EX

Spain

Hospital Sant Joan De Deu

Esplugues De Llobregas, Barcelona, Spain, 08950

Hospital Universitari i Politecnic La Fe de Valencia; Servicio de Farmacia

Valencia, Spain, 46026

Sweden

Drottning Silvias Barn- och ungdomssjukhus; Kliniken for barnmedicin

Goeteborg, Sweden, 41685

United Kingdom

Alder Hey Children s Hospital; Department of Pediatrics

Liverpool, United Kingdom, L12 2AP

UCL Institute of Child Health & Great Ormond Street Hospital for Children

London, United Kingdom, WC1N 1EH

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

  Study Documents (Full-Text)

Documents provided by Hoffmann-La Roche:

Study Protocol  [PDF] August 16, 2018

Statistical Analysis Plan  [PDF] October 11, 2019

More Information

Additional Information:

FDA Safety Alerts and Recalls 

Provides information about the Roche clinical trial NCT03039686 and molecule being investigated in Duchenne 

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03039686
• Other Study ID Numbers: CN001-016; 2016-001654-18 ( EudraCT Number ); WN40227 ( Other Identifier: Hoffman-La Roche )
• First Posted: February 1, 2017
• Results First Posted: December 21, 2020
• Last Update Posted: December 21, 2020
• Last Verified: November 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hoffmann-La Roche:

muscular dystrophy; Duchenne's Muscular Dystrophy; DMD

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked