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

Duchenne Muscular Dystrophy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03039686
• Other study ID #: CN001-016
• Secondary ID: 2016-001654-18WN
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 6, 2017
• Est. completion date: April 28, 2020

Study information

• Verified date: November 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 166
• Est. completion date: April 28, 2020
• Est. primary completion date: April 28, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 6 Years to 11 Years

Eligibility

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.

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• RO7239361
Take RO7239361 subcutaneously on specified days over a 48 week blinded period
• Placebo for RO7239361
Take placebo subcutaneously on specified days over a 48 week blinded period

Locations

Country	Name	City	State
Argentina	Instituto centenario	Buenos Aires
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Lady Cilento Children's Hospital; Neurosciences Department	South Brisbane	Queensland
Australia	Children's Hospital Westmead; Paediatrics & Child Health	Westmead	New South Wales
Belgium	UZ Gent	Gent
Canada	London Health Sciences Centre; Children's Hospital; Pediatrics	London	Ontario
Canada	Children'S Hospital of Eastern Ontario	Ottawa	Ontario
France	Hospices Civils de Lyon	Lyon
France	Hotel Dieu; Service Pharmacie Essais Cliniques	Nantes
France	Hopital Armand Trousseau; centre reference Maladies Neuro-musculaires Est parisien Neuropediatrie	Paris Cedex 12
France	Hopitaux Universitaires de Strasbourg	Strasbourg
Germany	Universitatsklinikum Essen; Innere Klinik	Essen
Italy	Az. Osp. Universitaria Pol. G. Martino; Dip. Neuroscienze, Scienze Psichiatriche e Anest.	Messina	Sicilia
Italy	Fondazione Serena Onlus - CENTRO CLINICO NEMO	Milano	Emilia-Romagna
Italy	Fondazione Policlinico Universitario A Gemelli; Servizio di Farmacia	Rome	Lazio
Japan	Hyogo College of Medicine Hospital	Hyogo
Japan	Miyagi Children's Hospital	Miyagi
Japan	Shinshu University Hospital	Nagano
Japan	National Hospital Organization Osaka Toneyama Medical Center	Osaka
Japan	National Center of Neurology and Psychiatry	Tokyo
Netherlands	Leids Universitair Medisch Centrum	Leiden
Netherlands	Radboud University Nijmegen Medical Centre; Ophthalmology	Nijmegen
Spain	Hospital Sant Joan De Deu	Esplugues De Llobregas	Barcelona
Spain	Hospital Universitari i Politecnic La Fe de Valencia; Servicio de Farmacia	Valencia
Sweden	Drottning Silvias Barn- och ungdomssjukhus; Kliniken for barnmedicin	Goeteborg
United Kingdom	Alder Hey Children s Hospital; Department of Pediatrics	Liverpool
United Kingdom	UCL Institute of Child Health & Great Ormond Street Hospital for Children	London
United States	Rare Disease Research, LLC	Atlanta	Georgia
United States	Kennedy Krieger Institute	Baltimore	Maryland
United States	Rush University Medical Center - PPDS	Chicago	Illinois
United States	Cincinnati Childrens Hospital Medical Center;Investigational Pharmacy	Cincinnati	Ohio
United States	Nationwide Childrens Hospital; Research Institute at Nationwide Childrens Hospital	Columbus	Ohio
United States	University of Florida	Gainesville	Florida
United States	University of Iowa	Iowa City	Iowa
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Las Vegas Clinic	Las Vegas	Nevada
United States	Yale University School of Medicine ; Pulmonary & Critical Care	New Haven	Connecticut
United States	Nemours Children's Hospital	Orlando	Florida
United States	Stanford University	Palo Alto	California
United States	Neuromuscular Research Center	Phoenix	Arizona
United States	University of California Davis Medical Center	Sacramento	California
United States	Saint Louis Children's Hospital	Saint Louis	Missouri
United States	Seattle Children's Hospital	Seattle	Washington
United States	University of Massachusetts Memorial Childrens Medical Center; Department of Neurology	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Canada,  France,  Germany,  Italy,  Japan,  Netherlands,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Baseline Time for 4 Stair Climb	The time to complete the 4 stair climb was measured at baseline.	Baseline
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)

External Links

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