A Clinical Study to Assess Two Doses of GSK2402968 in Subjects With Duchenne Muscular Dystrophy (DMD)

NCT01462292 | Completed Phase 2 Results DMC

• 1 other identifier: 114876
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 14

Brief Summary

The purpose of this study is to determine if 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. Two doses of GSK2402968 and placebo will be used in this study.

Conditions

Muscular Dystrophies

Keywords

968; Duchenne Muscular Dystrophy; GSK2402968; DMD; Duchenne; GSK

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline in Muscle Function Using the 6 Minute Walking Distance

  The participants during this assessment 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 to stop earlier if they feel unable to continue. The total distance walked within the duration of 6 minutes (or until the participant stopped in case of early termination of the test), was recorded in meters. Change from Baseline, was defined as the post-randomization value minus the Baseline value. Baseline was defined as Week 0.

  Baseline (Week 0) and Week 24

Secondary Outcomes (17)

• Change From Baseline in Rise From Floor Time at Week 24

  Baseline (Week 0) and Week 24

• Change From Baseline in 4 Stair Climb Ascent/Descent Time at Week 24

  Baseline (Week 0) and Week 24

• Change From Baseline in 10 Meter Walk/Run at Week 24

  Baseline (Week 0) and Week 24

• Change From Baseline in Muscle Strength Total Score at Week 24

  Baseline (Week 0) and Week 24

• Change From Baseline in Muscle Strength Tests For-Knee Extensor, Knee Flexor, Hip Flexor, Elbow Flexor, Elbow Extensor, Shoulder Abductor at Week 24

  Baseline (Week 0) and Week 24

Study Arms (4)

GSK2402968 3 mg/kg/week

EXPERIMENTAL

3 mg/kg/week of investigational product

Drug: GSK2402968 3mg/kg/week

GSK2402968 6 mg/kg/week

EXPERIMENTAL

6 mg/kg/week of investigational Product

Drug: GSK2402968 6 mg/kg/week

Placebo to match GSK2402968 3 mg/kg/week

EXPERIMENTAL

Placebo

Drug: Placebo to match GSK2402968 3 mg/kg/week

Placebo to match GSK2402968 6 mg/kg/week

EXPERIMENTAL

Placebo

Drug: Placebo to match GSK2402968 6 mg/kg/week

Interventions

GSK2402968 3mg/kg/week DRUG

Comparison of 2 doses of GSK2402968

GSK2402968 3 mg/kg/week

GSK2402968 6 mg/kg/week DRUG

Comparison of 2 doses of GSK2402968

GSK2402968 6 mg/kg/week

Placebo to match GSK2402968 3 mg/kg/week DRUG

Matched placebo

Placebo to match GSK2402968 3 mg/kg/week

Placebo to match GSK2402968 6 mg/kg/week DRUG

Matched Placebo

Placebo to match GSK2402968 6 mg/kg/week

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 (DMD) 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,
• Life expectancy of at least 1 year,
• Able to rise from floor in \< or =15 seconds (without aids/orthoses) at Screening Visit 1 and Screening Visit 2,
• Able to complete 6 Minute Walk Distance (6MWD) test with minimal distance of at least 75 meters, with reproducible results (within 20% of each other) at Screening Visit 1, Screening Visit 2 and at the baseline visit prior to randomization,
• Receiving oral 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 48 week duration of the study (Dose adjustments that are based on weight changes are permitted),
• 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
• 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 disease or impairment including :
• Current or history of renal disease or impairment,
• Baseline platelet count below the Lower Limit of Normal,
• aPPT above the Upper Limit of Normal,
• History of significant medical disorder which may confound the interpretation of either efficacy or safety data e.g. inflammatory disease
• 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, 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 (14)

GSK Investigational Site

Sacramento, California, 95817, United States

Location

GSK Investigational Site

Stanford, California, 94305, United States

Location

GSK Investigational Site

Gulf Breeze, Florida, 32561, United States

Location

GSK Investigational Site

Iowa City, Iowa, 52242, United States

Location

GSK Investigational Site

Kansas City, Kansas, 66160, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21205, United States

Location

GSK Investigational Site

Minneapolis, Minnesota, 55455, United States

Location

GSK Investigational Site

St Louis, Missouri, 63110, United States

Location

GSK Investigational Site

New York, New York, 10032, United States

Location

GSK Investigational Site

Durham, North Carolina, 27710, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45229, United States

Location

GSK Investigational Site

Columbus, Ohio, 43205, United States

Location

GSK Investigational Site

Portland, Oregon, 97239, United States

Location

GSK Investigational Site

Dallas, Texas, 75207, United States

Location

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 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2011
• First Posted: October 31, 2011
• Study Start: October 26, 2011
• Primary Completion: May 21, 2013
• Study Completion: November 4, 2013
• Last Updated: October 16, 2017
• Results First Posted: October 16, 2017

Record last verified: 2017-08

Locations

US (14)