A Study to Assess Dystrophin Levels in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD) Who Have Been Treated With Ataluren

• Sponsor: PTC Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03796637
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arm: 1
• Actual Duration (Months): 1.7
• Patients Per Site Per Month: 3.4

Study Details

Study Description

Brief Summary

This study is designed to generate additional data on the effect of ataluren for producing dystrophin protein in nonsense mutation nmDMD participants. This study will evaluate dystrophin levels from participants with nmDMD who currently have been receiving ataluren for ≥9 months.

The study will have a single visit (Visit 1).

Condition or Disease	Intervention/Treatment	Phase
Duchenne Muscular Dystrophy	Drug: Ataluren	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Phase 2, Non-Interventional, Clinical Study to Assess Dystrophin Levels in Subjects With Nonsense Mutation Duchenne Muscular Dystrophy Who Have Been Treated With Ataluren for ≥9 Months
• Actual Study Start Date: Apr 11, 2019
• Actual Primary Completion Date: Jun 3, 2019
• Actual Study Completion Date: Jun 3, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: nmDMD Participants Participants who have been receiving ataluren, will be dosed daily 10 milligrams per kilogram (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening, for >=9 months from ongoing PTC-sponsored nmDMD clinical trials.	Drug: Ataluren; Ataluren will be administered as per the dose and schedule specified in the arm.; Other Names: PTC124

Outcome Measures

Primary Outcome Measures

1. Mean Dystrophin Levels as Measured by Electrochemiluminescence (ECL) [Day 1 of biopsy]

   The mean dystrophin protein levels were measured by ECL. Dystrophin levels are reported by muscle group (gastrocnemius, tibialis anterior, and across muscle locations). Results below the limit of quantitation were imputed as half of lower limit of quantitation (LLOQ). LLOQ = 0.5 micrograms (μg)/milliliter (mL)

Secondary Outcome Measures

1. Dystrophin Protein Levels as Determined by Immunohistochemistry [Day 1 of biopsy]

   Dystrophin levels by IHC mean membrane stain density are reported by muscle group (gastrocnemius, tibialis anterior, and across muscle locations).

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Evidence of signed and dated informed consent/assent document(s) indicating that the participant (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial.

• Ambulatory (10 meters walk/run in less than [<] 30 seconds) and functional grade on the Brooke Upper Extremity Scale of a 1 or a 2.

• Currently being treated with ataluren 10, 10, 20 mg/kg for >=9 months, with no gap in treatment of greater than (>) 1 month, in an ongoing PTC-sponsored nmDMD clinical trial prior to study entry.

• Phenotypic evidence of duchenne muscular dystrophy (DMD) based on the onset of characteristic clinical symptoms or signs (for example, proximal muscle weakness, waddling gait, and Gowers' maneuver) by 6 years of age and an elevated serum creatine kinase (CK). Medical documentation of phenotypic evidence of DMD needs to be provided upon request by the medical monitor.

• Willing to undergo muscle biopsy.

Exclusion Criteria:

• Known contra-indication to muscle biopsy (such as bleeding or clotting disorders).

• Exposure to another investigational drug within 2 months prior to study enrollment or ongoing participation in any non-ataluren interventional clinical trial.

• Requirement for daytime ventilator assistance or any use of invasive mechanical ventilation via tracheostomy. Note: Evening non-invasive mechanical ventilation such as use of bilevel positive airway pressure (Bi-PAP) therapy is allowed.

• Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder), medical history, physical findings or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Los Angeles (UCLA)	Los Angeles	California	United States	90025

Sponsors and Collaborators

• PTC Therapeutics

Investigators

• Study Director: Francesco Bibbiani, MD, PTC Therapeutics, Inc.

Study Documents (Full-Text)

• Study Protocol - Mar 20, 2019
• Statistical Analysis Plan - Feb 12, 2020

More Information

Publications

None provided.

• Responsible Party: PTC Therapeutics
• ClinicalTrials.gov Identifier: NCT03796637
• Other Study ID Numbers: PTC124-GD-046-DMD; 2019-001691-11
• First Posted: Jan 8, 2019
• Last Update Posted: Apr 5, 2022
• Last Verified: Feb 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne

Study Results

Participant Flow

Arm/Group Title	Ataluren
Arm/Group Description	Participants who had been receiving ataluren, were dosed daily 10 milligrams (mg)/kilogram (kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening, for ≥9 months from ongoing PTC-sponsored nmDMD clinical trials.
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Ataluren
Arm/Group Description	Participants who had been receiving ataluren, were dosed daily 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening, for ≥9 months from ongoing PTC-sponsored nmDMD clinical trials.
Overall Participants	6
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.2 (2.04)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	6 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	6 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	6 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Mean Dystrophin Levels as Measured by Electrochemiluminescence (ECL)
Description	The mean dystrophin protein levels were measured by ECL. Dystrophin levels are reported by muscle group (gastrocnemius, tibialis anterior, and across muscle locations). Results below the limit of quantitation were imputed as half of lower limit of quantitation (LLOQ). LLOQ = 0.5 micrograms (μg)/milliliter (mL)
Time Frame	Day 1 of biopsy

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants with a valid assessment of dystrophin level, as measured by ECL.

Arm/Group Title	Ataluren
Arm/Group Description	Participants who had been receiving ataluren, were dosed daily 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening, for ≥9 months from ongoing PTC-sponsored nmDMD clinical trials.
Measure Participants	6
Gastrocnemius	0.0844 (0.05874)
Tibialis Anterior	0.1002 (0.08060)
Across Muscle Locations	0.1054 (0.08300)

2. Secondary Outcome

Title	Dystrophin Protein Levels as Determined by Immunohistochemistry
Description	Dystrophin levels by IHC mean membrane stain density are reported by muscle group (gastrocnemius, tibialis anterior, and across muscle locations).
Time Frame	Day 1 of biopsy

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants with a valid assessment of dystrophin level, as measured by ECL.

Arm/Group Title	Ataluren
Arm/Group Description	Participants who had been receiving ataluren, were dosed daily 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening, for ≥9 months from ongoing PTC-sponsored nmDMD clinical trials.
Measure Participants	6
Gastrocnemius	0.28817 (0.220547)
Tibialis Anterior	0.26578 (0.226510)
Across Muscle Locations	0.30483 (0.218600)

Adverse Events

Time Frame	Baseline (Day 1) up to Week 1
Adverse Event Reporting Description	Safety population included all participants who received at least 1 dose of ataluren.
Arm/Group Title	Ataluren
Arm/Group Description	Participants who had been receiving ataluren, were dosed daily 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening, for ≥9 months from ongoing PTC-sponsored nmDMD clinical trials.
All Cause Mortality
	Ataluren
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Serious Adverse Events
	Ataluren
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	Ataluren
	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)
General disorders
Puncture site discharge	1/6 (16.7%)
Injury, poisoning and procedural complications
Procedural pain	2/6 (33.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor can review results and/or communications prior to public release and can embargo communications regarding trial results for a period that is up to 180 days from the time submitted to the sponsor for review. The sponsor may consult with the PI to require changes to the communication or extend the embargo.