Duchenne Muscular DystrophyPhase 1/2NCT02667483

Study of DS-5141b in Patients With Duchenne Muscular Dystrophy

A Phase 1/2 study testing DS-5141b in people with Duchenne Muscular Dystrophy, run by Daiichi Sankyo Co., Ltd. at 2 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a phase I/II study to evaluate the safety, tolerability, efficacy, and pharmacokinetic (PK) profile of DS-5141b in patients with Duchenne muscular dystrophy (DMD) amenable to exon 45 skipping and to determine the dosage for subsequent studies. Read more about this study

Who is it for?: Ages 5 to 10 years, men only
Conditions the study is for: Duchenne Muscular Dystrophy
What is being tested?: DS-5141b
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 8 participants
Where: 2 sitesJapan
Study dates: Oct 2015to 20 Oct 2020
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 5 to 10 years
Men only
No healthy volunteers
Child

Who may be able to join

Confirmation of out-of-frame deletion(s) that could be corrected by dystrophin gene exon 45 skipping.
Intact muscles of adequate quality for biopsy to allow evaluation of the efficacy of the study drug.
Boys aged from 5 years to <11 years.
Patients able to walk at least 325 meters in the 6-minutes walk test.
Glucocorticoid-naive patients, or patients who have used glucocorticoids for at least 6 months prior to enrollment in this study with no dose changes for at least 3 months prior to enrollment.

Who cannot join

A genetic mutation that can not be expected the expression of dystrophin protein by dystrophin gene exon 45 skipping.
A concurrent illness other than DMD that can cause muscle weakness and/or impairment of motor function.
Current or history of severe disorder.
Left ventricular ejection fraction (LEVF) <55%.
Corrected QT interval (QTc) >0.45 sec.

Trial locations and contacts

2 sites in 1 country.

Japan2 sites

Kobe University Hospital
Hyōgo, Kobe-shi, 650-0017
National Center of Neurology and Psychiatry
Tokyo, Kodaira-shi, 187-8551

Other trials in Japan

About this study

Official title: Phase I/II Study of DS-5141b: Open-label Study of DS-5141b in Patients With Duchenne Muscular Dystrophy

Conditions: Duchenne Muscular Dystrophy
Being tested: DS-5141b
Keywords: Duchenne muscular dystrophy, DMD, Oligonucleotides, Antisense, Exon skipping
Medical subject headings: Muscular Dystrophy, Duchenne

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DS-5141bDrug
DS-5141b, Subcutaneous injection

Study groups in NCT02667483
Study group	Role	What they receive
DS-5141b	Experimental	DS-5141b, Subcutaneous injection Part 1: DS-5141b will be injected subcutaneously once a week for 2 weeks at the following dose levels. Dose escalation will be performed. DS-5141b will be administered at dose levels 1 and 3 in Cohort 1 and at dose levels 2 and 4 in Cohort 2. * Level 1: 0.1 mg/kg * Level 2: 0.5 mg/kg * Level 3: 2.0 mg/kg * Level 4: 6.0 mg/kg Part 2: Two doses of DS-5141b will be selected based on the results obtained in Part 1. Each selected dose will be administered subcutaneously once a week for 12 weeks. Part 2-Extension-2: Two doses, 2.0 mg/kg or 6.0 mg/kg, of DS-5141b will be administered subcutaneously once a week for 48 weeks. Receives: Drug: DS-5141b

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE) In Participants With Duchenne Muscular Dystrophy
A treatment-emergent adverse event (TEAE) is defined as an adverse event that emerges during treatment having been absent prior to treatment or reemerges during treatment or worsens in severity during treatment.
Measured: 48 Weeks of Part 2-Extension-2
Pharmacokinetic Parameter Maximum Concentration (Cmax) of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy
Pharmacokinetic parameters were assessed using non-compartmental methods.
Measured: Week 48 of Part 2-Extension-2
Pharmacokinetic Parameter Area Under the Curve (AUC) Tau of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy
Pharmacokinetic parameters were assessed using non-compartmental methods.
Measured: Week 48 of Part 2-Extension-2
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy
Pharmacokinetic parameters were assessed using non-compartmental methods.
Measured: Week 48 of Part 2-Extension-2
Pharmacokinetic Parameter Half-life (T1/2) of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Dystrophy
Pharmacokinetic parameters were assessed using non-compartmental methods.
Measured: Week 48 of Part 2-Extension-2
Mean Dystrophin Protein Expression in Muscle Tissue
Measured: Week 48 of Part 2-Extension-2

Secondary outcomes (1)

Number of Participants With Exon 45-skipped Dystrophin mRNA Expression in Muscle Tissue Posttreatment
Measured: Week 48 of Part 2-Extension-2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 201520 Oct 2020

First posted29 Jan 2016 (estimated)
Study startOct 2015
Primary completion20 Oct 2020
Study completion20 Oct 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Duchenne Muscular DystrophyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02667483
Sponsor's protocol ID: DS5141-A-J101
Other IDs: 153072
Status last verified: Jul 2023
First submitted: 26 Jan 2016
Last updated: 7 Mar 2024
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingEarly Phase 1
Safety and Dystrophin Expression of SPOT-03 in Duchenne Muscular Dystrophy (DMD) Patients
Duchenne Muscular Dystrophy (DMD)
RecruitingPhase 2
Safety and Efficacy of KER-065 in Participants With Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy
Not yet recruitingPhase 2
A Phase 2 Trial to Investigate the Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tegacorat in Male Participants 4 to <7 Years of Age With Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy (DMD)
Not yet recruitingObservational study
Multimodal Study About Absence of Dp140 in Becker Muscular Dystrophy: Brain-muscle Imaging, Cognition and Muscle Function
Becker Muscular Dystrophy
Enrolling by invitationObservational study
A Long-term Observational Study Evaluating Eteplirsen, Golodirsen, or Casimersen in Routine Clinical Practice
Duchenne Muscular Dystrophy

All Duchenne Muscular Dystrophy trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I/II Study of DS-5141b: Open-label Study of DS-5141b in Patients With Duchenne Muscular Dystrophy
ClinicalTrials.gov ID: NCT02667483
Acronym / sponsor ID: DS5141-A-J101
Conditions: Duchenne Muscular Dystrophy
Keywords: Duchenne muscular dystrophy, DMD, Oligonucleotides, Antisense, Exon skipping
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 8 participants (actual)
Lead sponsor: Daiichi Sankyo Co., Ltd.Industry (pharma, biotech, devices)
Collaborators: Daiichi Sankyo
Study start: Oct 2015 (actual)
Primary completion: 20 Oct 2020 (actual)
Study completion: 20 Oct 2020 (actual)
First posted: 29 Jan 2016 (estimated)
Results: Posted 7 Mar 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
DS-5141b	Experimental	Drug: DS-5141bDS-5141b, Subcutaneous injection Part 1: DS-5141b will be injected subcutaneously once a week for 2 weeks at the following dose levels. Dose escalation will be performed. DS-5141b will be administered at dose levels 1 and 3 in Cohort 1 and at dose levels 2 and 4 in Cohort 2. * Level 1: 0.1 mg/kg * Level 2: 0.5 mg/kg * Level 3: 2.0 mg/kg * Level 4: 6.0 mg/kg Part 2: Two doses of DS-5141b will be selected based on the results obtained in Part 1. Each selected dose will be administered subcutaneously once a week for 12 weeks. Part 2-Extension-2: Two doses, 2.0 mg/kg or 6.0 mg/kg, of DS-5141b will be administered subcutaneously once a week for 48 weeks.

Who may qualify

Ages: 5 to 10 years
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (5 listed)

Confirmation of out-of-frame deletion(s) that could be corrected by dystrophin gene exon 45 skipping.
Intact muscles of adequate quality for biopsy to allow evaluation of the efficacy of the study drug.
Boys aged from 5 years to <11 years.
Patients able to walk at least 325 meters in the 6-minutes walk test.
Glucocorticoid-naive patients, or patients who have used glucocorticoids for at least 6 months prior to enrollment in this study with no dose changes for at least 3 months prior to enrollment.

Key exclusion criteria (5 listed)

A genetic mutation that can not be expected the expression of dystrophin protein by dystrophin gene exon 45 skipping.
A concurrent illness other than DMD that can cause muscle weakness and/or impairment of motor function.
Current or history of severe disorder.
Left ventricular ejection fraction (LEVF) <55%.
Corrected QT interval (QTc) >0.45 sec.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DS-5141bDS-5141b, Subcutaneous injection	Drug	DS-5141b

Primary outcome

Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE) In Participants With Duchenne Muscular Dystrophy
Time frame: 48 Weeks of Part 2-Extension-2
A treatment-emergent adverse event (TEAE) is defined as an adverse event that emerges during treatment having been absent prior to treatment or reemerges during treatment or worsens in severity during treatment.
Pharmacokinetic Parameter Maximum Concentration (Cmax) of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy
Time frame: Week 48 of Part 2-Extension-2
Pharmacokinetic parameters were assessed using non-compartmental methods.
Pharmacokinetic Parameter Area Under the Curve (AUC) Tau of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy
Time frame: Week 48 of Part 2-Extension-2
Pharmacokinetic parameters were assessed using non-compartmental methods.
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy
Time frame: Week 48 of Part 2-Extension-2
Pharmacokinetic parameters were assessed using non-compartmental methods.
Pharmacokinetic Parameter Half-life (T1/2) of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Dystrophy
Time frame: Week 48 of Part 2-Extension-2
Pharmacokinetic parameters were assessed using non-compartmental methods.
Mean Dystrophin Protein Expression in Muscle Tissue
Time frame: Week 48 of Part 2-Extension-2

1 secondary outcome

Number of Participants With Exon 45-skipped Dystrophin mRNA Expression in Muscle Tissue Posttreatment
Time frame: Week 48 of Part 2-Extension-2

Results and safety

Results posted to the registry on 7 Mar 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
DS-5141b 2.0 mg/kg	3	3
DS-5141b 6.0 mg/kg	5	5

Primary outcome: Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE) In Participants With Duchenne Muscular Dystrophy

Time frame: 48 Weeks of Part 2-Extension-2. Count of participants. Unit: Participants

Measure	All: DS-5141b 2.0 mg/kg n = 3	All: DS-5141b 6.0 mg/kg n = 5
Value	3	5

Population analysed: Safety events were assessed in the Safety Analysis Set.

Primary outcome: Pharmacokinetic Parameter Maximum Concentration (Cmax) of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy

Time frame: Week 48 of Part 2-Extension-2. Mean (Standard Deviation). Unit: ng/mL

Measure	All: DS-5141b 2.0 mg/kg n = 3	All: DS-5141b 6.0 mg/kg n = 5
Value	1320 (293)	5190 (2590)

Population analysed: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.

Primary outcome: Pharmacokinetic Parameter Area Under the Curve (AUC) Tau of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy

Time frame: Week 48 of Part 2-Extension-2. Mean (Standard Deviation). Unit: ng*h/mL

Measure	All: DS-5141b 2.0 mg/kg n = 3	All: DS-5141b 6.0 mg/kg n = 4
Value	23100 (5920)	102000 (45600)

Population analysed: Pharmacokinetic parameters were assessed in participants with available data in the Pharmacokinetic Analysis Set.

Primary outcome: Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy

Time frame: Week 48 of Part 2-Extension-2. Median (Full Range). Unit: hours

Measure	All: DS-5141b 2.0 mg/kg n = 3	All: DS-5141b 6.0 mg/kg n = 5
Value	1.98 (1.88 to 4.10)	4.07 (3.93 to 8.00)

Population analysed: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Adverse events were collected from baseline up to 48 weeks post extension period.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
DS-5141b 2.0 mg/kg	0 of 3 (0%)	3 of 3 (100%)	0 of 3
DS-5141b 6.0 mg/kg	1 of 5 (20%)	5 of 5 (100%)	0 of 5

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Duchenne Muscular Dystrophy

RecruitingEarly Phase 1
Safety and Dystrophin Expression of SPOT-03 in Duchenne Muscular Dystrophy (DMD) Patients
Duchenne Muscular Dystrophy (DMD)
RecruitingPhase 2
Safety and Efficacy of KER-065 in Participants With Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy
Not yet recruitingPhase 2
A Phase 2 Trial to Investigate the Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tegacorat in Male Participants 4 to <7 Years of Age With Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy (DMD)
Not yet recruitingObservational study
Multimodal Study About Absence of Dp140 in Becker Muscular Dystrophy: Brain-muscle Imaging, Cognition and Muscle Function
Becker Muscular Dystrophy
Enrolling by invitationObservational study
A Long-term Observational Study Evaluating Eteplirsen, Golodirsen, or Casimersen in Routine Clinical Practice
Duchenne Muscular Dystrophy

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Global Clinical Leader study director

Daiichi Sankyo

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing DS-5141b in people with Duchenne Muscular Dystrophy, run by Daiichi Sankyo Co., Ltd. at 2 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE) In Participants With Duchenne Muscular Dystrophy (time frame: 48 Weeks of Part 2-Extension-2). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02667483.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2024.