Phase I/II Study of SRP-4053 in DMD Patients

NCT ID: NCT02310906

Last Updated: 2020-10-19

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

39 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-01-13

Study Completion Date

2019-03-25

Brief Summary

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This is a first-in-human, multiple-dose 2-part study to assess the safety, tolerability, efficacy, and pharmacokinetics of SRP-4053 in Duchenne muscular dystrophy (DMD) patients with deletions amenable to exon 53 skipping.

Detailed Description

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Part 1: Randomized, placebo-controlled dose-titration to assess safety, tolerability and pharmacokinetics of 4 dose levels of SRP-4053 in genotypically-confirmed DMD patients with deletions amenable to exon 53 skipping.

Part 2: Open-label evaluation of SRP-4053 in patients from Part 1, along with newly enrolled DMD patients with deletions amenable to exon 53 skipping and an untreated group of DMD patients with deletions not amenable to exon 53 skipping.

Safety, including adverse event monitoring and routine laboratory assessments, will be followed on an ongoing basis for all patients.

Clinical efficacy, including functional tests such as the six-minute walk test (6MWT), will be assessed at regularly scheduled study visits. Patients in the treated groups will undergo one baseline and one follow-up muscle biopsy. Patients in the untreated group will not undergo biopsies and will follow an abbreviated schedule of study assessments.

Conditions

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Duchenne Muscular Dystrophy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Masking Description: Part 1 is double-blind and randomized; Part 2 is open-label.

Study Groups

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Part 1: SRP-4053

Patients will receive SRP-4053 (golodirsen) intravenous (IV) infusions, weekly, at escalating dose levels as follows: Weeks 1-2, 4 mg/kg/week; Weeks 3-4, 10 mg/kg/week; Weeks 5-6, 20 mg/kg/week; Weeks 7-12, 30 mg/kg/week. Dosing will be interrupted or halted if specific predefined stopping criteria are met or if warranted at the discretion of the Sponsor or Investigator.

Group Type EXPERIMENTAL

SRP-4053

Intervention Type DRUG

SRP-4053 (golodirsen) solution for IV infusion.

Part 1: Placebo

Patients will receive SRP-4053 placebo-matching IV infusions, weekly, for 12 weeks. Dosing will be interrupted or halted if specific predefined stopping criteria are met or if warranted at the discretion of the Sponsor or Investigator.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

SRP-4053 placebo-matching solution for IV infusion.

Part 2: SRP-4053

All eligible patients from Part 1, as well as new patients, will receive SRP-4053 (golodirsen) 30 mg/kg/week IV infusions, weekly, for up to 168 weeks.

Group Type EXPERIMENTAL

SRP-4053

Intervention Type DRUG

SRP-4053 (golodirsen) solution for IV infusion.

Part 2: Untreated Group

Patients with DMD who have a genotypically confirmed deletion of exon(s) not amenable to treatment by exon 53 skipping, but who otherwise meet the same eligibility criteria as treated patients newly recruited to Part 2, will undergo the same study assessments as treated Patients (except for pharmacokinetic \[PK\] sampling and muscle biopsies), but at a reduced schedule through Week 144. The untreated patients are not considered as control group.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Placebo

SRP-4053 placebo-matching solution for IV infusion.

Intervention Type DRUG

SRP-4053

SRP-4053 (golodirsen) solution for IV infusion.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Diagnosed with DMD, genotypically confirmed.
* Intact right and left biceps muscles or an alternative upper arm muscle group.
* Stable pulmonary and cardiac function.
* Minimum performance on 6MWT, North Star Ambulatory Assessment, and rise (Gowers) test as specified in the study protocol.
* On a stable dose of corticosteroids for at least 6 months.

Exclusion Criteria

* Previous treatment with the experimental agents BMN-195 (SMT C1100) or PRO053.
* Current or previous treatment with any other experimental treatments within 12 weeks prior to study entry.
* Major surgery within the last 3 months.
* Presence of other clinically significant illness.
* Major change in physical therapy regime within the last 3 months.
Minimum Eligible Age

6 Years

Maximum Eligible Age

15 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Institut de Myologie, France

OTHER

Sponsor Role collaborator

Consultants for Research in Imaging and Spectroscopy

OTHER

Sponsor Role collaborator

Great Ormond Street Hospital for Children NHS Foundation Trust

OTHER

Sponsor Role collaborator

Catholic University of the Sacred Heart

OTHER

Sponsor Role collaborator

Royal Holloway University

OTHER

Sponsor Role collaborator

SYSNAV

INDUSTRY

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role collaborator

University of Newcastle Upon-Tyne

OTHER

Sponsor Role collaborator

Sarepta Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Sarepta Therapeutics, Inc.

Locations

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Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

Institute de Myologie

Paris, , France

Site Status

Policlinico Universitario A Gemelli

Rome, , Italy

Site Status

Great Ormond Street Hospital for Children NHS Foundation Trust

London, , United Kingdom

Site Status

Newcastle University Hospital

Newcastle, , United Kingdom

Site Status

Countries

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United States France Italy United Kingdom

References

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Frank DE, Schnell FJ, Akana C, El-Husayni SH, Desjardins CA, Morgan J, Charleston JS, Sardone V, Domingos J, Dickson G, Straub V, Guglieri M, Mercuri E, Servais L, Muntoni F; SKIP-NMD Study Group. Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy. Neurology. 2020 May 26;94(21):e2270-e2282. doi: 10.1212/WNL.0000000000009233. Epub 2020 Mar 5.

Reference Type BACKGROUND
PMID: 32139505 (View on PubMed)

Servais L, Mercuri E, Straub V, Guglieri M, Seferian AM, Scoto M, Leone D, Koenig E, Khan N, Dugar A, Wang X, Han B, Wang D, Muntoni F; SKIP-NMD Study Group. Long-Term Safety and Efficacy Data of Golodirsen in Ambulatory Patients with Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A First-in-human, Multicenter, Two-Part, Open-Label, Phase 1/2 Trial. Nucleic Acid Ther. 2022 Feb;32(1):29-39. doi: 10.1089/nat.2021.0043. Epub 2021 Nov 17.

Reference Type DERIVED
PMID: 34788571 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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4053-101

Identifier Type: -

Identifier Source: org_study_id

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