Last updated: 07/17/2024 15:36:13
A clinical study to assess the efficacy and safety of GSK2402968 in subjects with Duchenne muscular dystrophyDMD114044
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A phase III, randomized, double blind, placebo-controlled clinical study to assess the efficacy and safety of GSK2402968 in subjects with Duchenne muscular dystrophy
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Change from Baseline in muscle function using the 6 Minute Walking Distance (6MWD) test assessed at Week 48
Timeframe: Baseline (Day 0) and Week 48
Secondary outcomes:
Change from Baseline in the linearized North Star Ambulatory Assessment (NSAA) total score at Week 48
Timeframe: Baseline (Day 0) and Week 48
Change from Baseline in the 4 stair climb (ascent) velocity at Week 48
Timeframe: Baseline (Day 0) and Week 48
Change from Baseline in the 10-meter walk/run velocity at Week 48
Timeframe: Baseline (Day 0) and Week 48
Change from Baseline in the timed function test Rise from floor at Week 48
Timeframe: Baseline (Day 0) and Week 48
Change from Baseline in the 4 stair climb (descent) velocity at Week 48
Timeframe: Baseline (Day 0) and Week 48
Change from Baseline in muscle strength (total score) at Week 48
Timeframe: Baseline (Day 0) and Week 48
Kaplan-Meier Estimates for Time to loss of ambulation
Timeframe: Week 48
Number of participants who experienced accidental falls during 6MWD assessments at Week 48
Timeframe: Week 48
Change from Baseline in creatine kinase serum concentrations at Week 48
Timeframe: Baseline (Day 0) and Week 48
Change from Baseline in Pulmonary Function test Forced vital capacity (FVC) and Forced expiratory volume in 1 second (FEV1) at Week 48
Timeframe: Baseline (Day 0) and Week 48
Number of participants with Identified Mutation: DMD Exon 51 skip (upon muscle biopsies) at Week 48
Timeframe: Week 48
Change from Baseline in Pediatric Quality of Life (PedsQL) Total Score at Week 48
Timeframe: Baseline (Day 0) and Week 48
Change from Baseline in Pulmonary Function test peak cough flow (PCF) and peak flow (PF) at Week 48
Timeframe: Baseline (Day 0) and Week 48
Number of participants who showed improvement on Clinician Global Impression of Improvement (CGI-I) scale at Week 48
Timeframe: Week 48
Change from Baseline in Health Utilities Index (HUI) Scores at Week 48
Timeframe: Baseline (Randomization Visit, Day 0) and Week 48
Number of participants with adverse events (AE) and severe adverse events (SAE)
Timeframe: Up to Follow-up (Week 68)
Number of participants with vital sign data for systolic blood pressure (SBP) and diastolic blood pressure (DBP) and heart rate (HR) of potential clinical concern (PCC) at any visit post-Baseline
Timeframe: Up to Week 48
Number of participants with abnormal-clinically significant Electrocardiogram (ECG) findings at any visit post-Baseline
Timeframe: Up to Week 48
Number of participants with hematology parameters of PCC at any visit post-Baseline
Timeframe: Up to Week 48
Number of participants with coagulation parameters of PCC at any visit post-Baseline
Timeframe: Up to Week 48
Number of participants with clinical chemistry parameters of PCC at any visit post-Baseline
Timeframe: Up to Week 48
Number of participants with urinalysis data outside the reference range (>reference range high) at any visit post- Baseline
Timeframe: Up to Week 48
Plasma Concentrations of GSK2402968 Following Subcutaneous Administration
Timeframe: Randomization (Week 0 at 0.5, 1 and 3 hours), Week 8 (pre-dose, 1-4 hours), Week 12 (pre-dose, 1-4 hours), Week 24 (pre-dose, 1-4 hours), Week 36 (pre-dose, 1-4 hours), Week 47 (pre-dose, 1-4 hours)
Interventions:
Drug: GSK2402968 6mg/kg/week
Enrollment:
186
Observational study model:
Not applicable
Primary completion date:
2013-28-06
Time perspective:
Not applicable
Clinical publications:
Kevin M. Flanigana, Thomas Voitb, Xiomara Q. Rosalesa, Laurent Servaisb, John E. Krausc, Claire Wardelld, Allison Morgane, Susie Dorricotte, Joanna Nakielnyd, Naashika Quarcood, Lia Liefaardf, Tom Druryd, Giles Campione, Padraig Wright. Pharmacokinetics and safety of single doses of drisapersen in non-ambulant subjects with Duchenne muscular dystrophy: Results of a double-blind randomized clinical trial. N Engl J Med. 2018;28(1):4-15
Medical condition
Muscular Dystrophies
Product
drisapersen
Collaborators
Not applicable
Study date(s)
December 2010 to June 2013
Type
Interventional
Phase
3
Participation criteria
Sex
Male
Age
5+ years
Accepts healthy volunteers
No
- 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.
- Any additional missing exon for DMD that cannot be treated with GSK2402968
- Current or history of liver or renal disease or impairment
Inclusion and exclusion criteria
Inclusion criteria:
- 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).
- French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Exclusion criteria:
- 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,
- Symptomatic cardiomyopathy. If subject has a left ventricular ejection fraction <45% at Screening, the investigator should discuss inclusion of subject in the study with the medical monitor,
- 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.
Trial location(s)
Location
GSK Investigational Site
Buenos Aries, Buenos Aires, Argentina, C1425AWC
Status
Study Complete
Location
GSK Investigational Site
Esplugues de Llobregat. Barcelona, Spain, 08950
Status
Study Complete
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45122
Status
Study Complete
Location
GSK Investigational Site
Freiburg, Baden-Wuerttemberg, Germany, 79106
Status
Study Complete
Location
GSK Investigational Site
Goettingen, Niedersachsen, Germany, 37075
Status
Study Complete
Location
GSK Investigational Site
Kiel, Schleswig-Holstein, Germany, 24105
Status
Study Complete
Location
GSK Investigational Site
Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
Status
Study Complete
Location
GSK Investigational Site
Ribeirao Preto, São Paulo, Brazil, 14048-900
Status
Study Complete
Location
GSK Investigational Site
Rio de Janeiro, Rio De Janeiro, Brazil, 21941-490
Status
Study Complete
Location
GSK Investigational Site
Santiago, Región Metro De Santiago, Chile
Status
Study Complete
Location
GSK Investigational Site
Santo Andre, São Paulo, Brazil, 09060-650
Status
Study Complete
Location
GSK Investigational Site
São Paulo, São Paulo, Brazil, 05403-900
Status
Study Complete
Location
GSK Investigational Site
Vancouver, British Columbia, Canada, V6H 3V4
Status
Study Complete
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2013-28-06
Actual study completion date
2013-28-06
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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