A Clinical Study to Assess the Efficacy and Safety of GSK2402968 in Subjects With Duchenne Muscular Dystrophy

NCT01254019 | Completed Phase 3 Results DMC

• 1 other identifier: 114044
• Study Type: interventional
• Target: 186
• Locations: 20 countries
• Sites: 47

Brief Summary

The purpose of this study is to determine whether GSK2402968 is effective in the treatment of ambulant boys with Duchenne muscular dystrophy resulting from a mutation thought to be corrected by exon 51 skipping.

Conditions

Muscular Dystrophies

Keywords

Duchenne Muscular Dystrophy; DMD; 968; GSK; Duchenne

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Muscle Function Using the 6 Minute Walking Distance (6MWD) Test Assessed at Week 48

  During the 6MWD, participants were asked to walk, at their own preferred speed, up and down a fixed distance until they were told to stop after 6 minutes. The participants were warned of the time and were told that they may stop earlier if they feel unable to continue. The total distance walked within 6 minutes (or until the participant stopped in case of early termination of the test), the 6MWD, was recorded in meters as well as any falls. Baseline was defined as participants randomization assessment at Visit 3 (Day 0). Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48.

  Baseline (Day 0) and Week 48

Secondary Outcomes (23)

• Change From Baseline in the Linearized North Star Ambulatory Assessment (NSAA) Total Score at Week 48

  Baseline (Day 0) and Week 48

• Change From Baseline in the 4 Stair Climb (Ascent) Velocity at Week 48

  Baseline (Day 0) and Week 48

• Change From Baseline in the 10-meter Walk/Run Velocity at Week 48

  Baseline (Day 0) and Week 48

• Change From Baseline in the Timed Function Test Rise From Floor at Week 48

  Baseline (Day 0) and Week 48

• Change From Baseline in the 4 Stair Climb (Descent) Velocity at Week 48

  Baseline (Day 0) and Week 48

Study Arms (2)

GSK2402968

EXPERIMENTAL

6mg/kg

Drug: GSK2402968 6mg/kg/week

Placebo

EXPERIMENTAL

dose-matched

Drug: GSK2402968 6mg/kg/week

Interventions

GSK2402968 6mg/kg/week DRUG

subcutaneous

GSK2402968; Placebo

Eligibility Criteria

• Age: 5 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Ambulant subjects with Duchenne muscular dystrophy resulting from a mutation/deletion within the DMD gene, confirmed by a state-of-the-art DNA diagnostic technique covering all DMD gene exons, including but not limited to MLPA (Multiplex Ligation-dependent Probe Amplification), CGH (Comparative Genomic Hybridisation), SCAIP (Single Condition Amplification/Internal Primer) or H-RMCA (High-Resolution Melting Curve Analysis), and correctable by GSK2402968-induced DMD exon 51 skipping.
• Males, aged at least 5 years, and with life expectancy of at least 1 year
• Able to complete 6MWD test with minimal distance of at least 75m at each predrug visit. In addition, results of 6MWD must be within 20% of each other at each pre-drug visit
• Receiving glucocorticoids for a minimum of 6 months immediately prior to screening, with no significant change in total daily dosage or dosing regimen for a minimum of 3 months immediately prior to screening and a reasonable expectation that total daily dosage and dosing regimen will not change significantly for the duration of the study
• QTc \<450msec (based on single or average QTc value of triplicate ECGs obtained over a brief recording period), or \<480 msec for subjects with Bundle Branch Block. Note: QTc may be either QTcB or QTcF, and machine read or manual overread.
• Subjects, where appropriate, must be willing to use adequate contraception (condoms or abstinence) for the duration of the study and for at least 5 months after the last dose of study drug.
• Willing and able to comply with all protocol requirements and procedures,
• Able to give informed assent and/or consent in writing signed by the subject and/or parent(s)/legal guardian (according to local regulations).

You may not qualify if:

• Any additional missing exon for DMD that cannot be treated with GSK2402968
• Current or history of liver or renal disease or impairment
• Acute illness within 4 weeks of the first anticipated administration of study medication which may interfere with study assessments
• Use of anticoagulants, antithrombotics or antiplatelet agents, previous treatment with investigational drugs, within 6 months of the first administration of study medication; and idebenone or other forms of Coenzyme Q10 within 1 month of the first administration of study medication.
• Current or anticipated participation in any investigational clinical studies
• Positive hepatitis B surface antigen, hepatitis C antibody test (if verified via RIBA or PCA testing), or human immunodeficiency virus (HIV) test at screening,
• Children in Care. The definition of a Child in Care is a child who has been placed under the control or protection of an agency, organisation, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation. The definition of a child in care can include a child cared for by foster parents or living in a care home or institution, provided that the arrangement falls within the definition above. The definition of a child in care does not include a child who is adopted or has an appointed legal guardian.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (47)

GSK Investigational Site

Buenos Aries, Buenos Aires, C1425AWC, Argentina

Location

GSK Investigational Site

Leuven, 3000, Belgium

Location

GSK Investigational Site

Curitiba, Paraná, 80250-060, Brazil

Location

GSK Investigational Site

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

GSK Investigational Site

Ribeirão Preto, São Paulo, 14048-900, Brazil

Location

GSK Investigational Site

Santo André, São Paulo, 09060-650, Brazil

Location

GSK Investigational Site

Rio de Janeiro, 21941-490, Brazil

Location

GSK Investigational Site

São Paulo, 05403-900, Brazil

Location

GSK Investigational Site

Vancouver, British Columbia, V6H 3V4, Canada

Location

GSK Investigational Site

London, Ontario, N6A 4G5, Canada

Location

GSK Investigational Site

Montreal, Quebec, H1T 1C9, Canada

Location

GSK Investigational Site

Santiago, Región Metro de Santiago, 7500539, Chile

Location

GSK Investigational Site

Santiago, Región Metro de Santiago, Chile

Location

GSK Investigational Site

Santiago, 8330074, Chile

Location

GSK Investigational Site

Brno, 613 00, Czechia

Location

GSK Investigational Site

Prague, Czechia

Location

GSK Investigational Site

Koebenhavn Oe, 2100, Denmark

Location

GSK Investigational Site

Lille, 59037, France

Location

GSK Investigational Site

Marseille, 13385, France

Location

GSK Investigational Site

Nantes, 44093, France

Location

GSK Investigational Site

Paris, 75743, France

Location

GSK Investigational Site

Toulouse, 31059, France

Location

GSK Investigational Site

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

GSK Investigational Site

Munich, Bavaria, 80337, Germany

Location

GSK Investigational Site

Göttingen, Lower Saxony, 37075, Germany

Location

GSK Investigational Site

Essen, North Rhine-Westphalia, 45122, Germany

Location

GSK Investigational Site

Kiel, Schleswig-Holstein, 24105, Germany

Location

GSK Investigational Site

Budapest, 1095, Hungary

Location

GSK Investigational Site

Ferrara, Emilia-Romagna, 44100, Italy

Location

GSK Investigational Site

Rome, Lazio, 00165, Italy

Location

GSK Investigational Site

Rome, Lazio, 00168, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20122, Italy

Location

GSK Investigational Site

Messina, Sicily, 98125, Italy

Location

GSK Investigational Site

Hyōgo, 650-0017, Japan

Location

GSK Investigational Site

Kumamoto, 860-8556, Japan

Location

GSK Investigational Site

Saitama, 349-0196, Japan

Location

GSK Investigational Site

Tokyo, 187-8551, Japan

Location

GSK Investigational Site

Leiden, 2333 ZA, Netherlands

Location

GSK Investigational Site

Oslo, 0027, Norway

Location

GSK Investigational Site

Warsaw, 02-097, Poland

Location

GSK Investigational Site

Moscow, 125412, Russia

Location

GSK Investigational Site

Seoul, 110-744, South Korea

Location

GSK Investigational Site

Esplugues de Llobregat. Barcelona, 08950, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Valencia, 46026, Spain

Location

GSK Investigational Site

Kaohsiung City, 80708, Taiwan

Location

GSK Investigational Site

Ankara, 06100, Turkey (Türkiye)

Location

Related Publications (1)

• Goemans N, Mercuri E, Belousova E, Komaki H, Dubrovsky A, McDonald CM, Kraus JE, Lourbakos A, Lin Z, Campion G, Wang SX, Campbell C; DEMAND III study group. A randomized placebo-controlled phase 3 trial of an antisense oligonucleotide, drisapersen, in Duchenne muscular dystrophy. Neuromuscul Disord. 2018 Jan;28(1):4-15. doi: 10.1016/j.nmd.2017.10.004. Epub 2017 Dec 6.

  PMID: 29203355 DERIVED

MeSH Terms

Conditions

Muscular Dystrophies; Muscular Dystrophy, Duchenne

Condition Hierarchy (Ancestors)

Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2010
• First Posted: December 6, 2010
• Study Start: December 2, 2010
• Primary Completion: June 28, 2013
• Study Completion: June 28, 2013
• Last Updated: January 28, 2019
• Results First Posted: January 28, 2019

Record last verified: 2017-09

Locations

KR (1); HU (1); RU (1); BR (6); AR (1); ES (3); NO (1); JP (4); CL (3); DK (1); TW (1); NL (1); IT (5); PL (1); FR (5); TU (1); BE (1); DE (5); CA (3); CZ (2)