Duchenne Muscular DystrophyPhase 1/2NCT01957059
A Phase I/II Study of BMN053 in Subjects With Duchenne Muscular Dystrophy (DMD)
A Phase 1/2 study testing Regimen Selection Phase Group 2, Regimen Selection Phase Group 3 and Treatment Phase Group 4 in people with Duchenne Muscular Dystrophy, run by BioMarin Pharmaceutical at 6 sites in 5 countries.
Trial summary
The purpose of the study is to see whether BMN053 is safe and effective to use as medication for Duchenne muscular dystrophy (DMD) patients with a mutation around location 53 in the DNA for the dystrophin protein. Read more about this study
- Who is it for?
- Ages 5 to 18 years, men only
- Conditions the study is for
- Duchenne Muscular Dystrophy
- What is being tested?
- Regimen Selection Phase Group 2, Regimen Selection Phase Group 3 and Treatment Phase Group 4
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 6 sitesin 5 countries
- Study dates
- Jun 2013to 3 Aug 2016
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 18 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Duchenne muscular dystrophy resulting from a mutation correctable by treatment with BMN053 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 HRMCA (High-Resolution Melting Curve Analysis).
- Ambulant boys aged at least 5 years on the day of first dosing able to walk for at least 300 metres in the 6 minute walking distance (6MWD) test. In addition, results of the 6MWD test must be within ±30 metres of each other at 2 of 3 pre-treatment visits (screen 1, 2 and baseline) prior to first BMN053 administration.
- Adequate quality for biopsy (confirmed with MRI) of the lateral head of the gastrocnemius muscle. Only under exceptional circumstances will an alternative muscle (preferably brachii) be considered for biopsy and only following discussion between the Principal Investigator and the BioMarin Medical Monitor.
- Life expectancy of at least 3 years after inclusion in the study.
- Glucocorticosteroid use which is stable for at least 3 months prior to first BMN053 administration. Subjects must have been receiving glucocorticosteroids for at least 6 months prior to the first BMN053 administration.
- Willing and able to adhere to the study visit schedule and other protocol requirements.
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- Written informed consent signed (by parent(s)/legal guardian and/or the subject, according to the local regulations).
- 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.
- Anticipated adequate vein access for intravenous (IV) infusion.
Who cannot join
- Current or history of liver disease or impairment.
- Current or history of renal disease or impairment.
- At least two aPTT above upper limit of normal (ULN) within the last month prior to first dose of BMN053.
- Screening platelet count below the lower limit of normal (LLN).
- Acute illness within 4 weeks prior to first dose of BMN053 which may interfere with the study assessments.
- Severe mental retardation and/or behavioural problems which, in the opinion of the Investigator, prohibit participation in this study.
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- Severe cardiomyopathy which, in the opinion of the Investigator prohibits participation in this study. If a subject has a left ventricular ejection fraction <45% at screening, the Investigator should discuss inclusion of the subject with the Medical Monitor.
- Expected need for daytime mechanical ventilation within the next year.
- Use of anticoagulants, antithrombotics or antiplatelet agents.
- Use of idebenone or other forms of coenzyme Q10 within 1 month prior to the start of the screening for the study.
- Use of nutritional or herbal supplements which, in the opinion of the Investigator, may influence muscle performance within 1 month prior to first dose of BMN053.
- Use of any other investigational product or participation in another trial with an investigational product, within 6 months prior to the start of the screening for the study.
Trial locations and contacts
6 sites in 5 countries.
6 sites in 5 countries
United Kingdom2 sites
Great Ormond Street Hospital for Children
London, WC1N 3JH
Institute of Genetic Medicine International Centre for Life
Newcastle, NE1 3BZ
About this study
Official title: A Phase I/II, Open-label, Dose Escalating With 48 Week Treatment Study to Assess the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of BMN053 (Previously Known as PRO053) in Subjects With Duchenne Muscular Dystrophy.
The purpose of the study is to see whether BMN053 is safe and effective to use as medication for Duchenne muscular dystrophy (DMD) patients with a mutation around location 53 in the DNA for the dystrophin protein.
Read the detailed description
A Phase I/II, open-label, dose escalating with 48-week treatment study to assess the safety and tolerability, pharmacokinetics, pharmacodynamics and efficacy of BMN 053 (previously known as PRO053) in subjects with Duchenne muscular dystrophy
- Conditions
- Duchenne Muscular Dystrophy
- Being tested
- Regimen Selection Phase Group 2, Regimen Selection Phase Group 3, Treatment Phase Group 4, Regimen Selection Phase Group 1 (COMPLETED), Dosing Extension
- Keywords
- DMD, Duchenne muscular dystrophy, Duchenne, BMN053, BioMarin
- 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.
Regimen Selection Phase Group 2Drug
All doses of BMN053 will be administered as IV infusions. The proposed doses are as follows:
- 3 mg/kg
Regimen Selection Phase Group 3Drug
All doses of BMN053 will be administered as IV infusions. The proposed doses are as follows:
- 4-6 mg/kg
Treatment Phase Group 4Drug
All doses of PRO053 will be administered as IV infusions. The proposed doses will be decided upon completion of the Regimen Selection Phase of Groups 2 and 3
Regimen Selection Phase Group 1 (COMPLETED)Drug
All doses of BMN053 have been administered as subcutaneous injections.
Dosing ExtensionDrug
All doses of PRO053 will be administered as IV infusions. The proposed doses will be decided upon completion of the Regimen Selection Phase of Groups 2 and 3 and the Treatment Phase Group 4.
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation phase | Experimental | In the dose-escalation phase, following screening assessment, two cohorts of three subjects each receive two single doses of BMN 053 in two study periods (i.e., four single doses in total per subject). In each study period they will receive BMN 053 by IV infusion and by SC injection (separated by one week). The proposed doses are 1 mg/kg (Cohort 1, study period 1), 3 mg/kg (Cohort 2, study period 1), 6 mg/kg (Cohort 1, study period 2) and 9 mg/kg (Cohort 2, study period 2). The actual doses may be amended or repeated based on emerging data from previous doses. Receives: Drug: Regimen Selection Phase Group 1 (COMPLETED) |
| Regimen selection | Experimental | After completion of the dose-escalation period of Cohort 1, the safety data of the subjects will be reviewed by a DSMB and if no safety concerns these subjects will continue to receive 6 mg/kg BMN053 weekly by SC injection for 48 weeks. 3 more treatment-naïve subjects will be entered into this Group. These 6 subjects will form Group 1 of the Regimen Selection phase who received 6 mg/kg SC. At the time of this amendment (4) this part of the study has been completed. Following completion of the dose-escalation study period of Cohort 2 (9 mg/kg), the planned review of the preliminary plasma PK data from the dose-escalation phase showed a relative bioavailability of 50% for BMN053 with SC dosing (50% lower plasma AUC after SC dosing compared to IV dosing). Taking into consideration the risk of injection site reactions noted with similar compounds when administered SC over longer term, the planned 9 mg/kg BMN053 weekly by SC injection will be discontinued to be replaced by an IV regimen. Receives: Drug: Regimen Selection Phase Group 2; Drug: Regimen Selection Phase Group 3 |
| 48-week Treatment Phase | Experimental | Thirty additional treatment-naïve subjects will be recruited for the primary evaluation and will receive treatment at the recommended regimen for a total of 48 weeks. Subjects dosed initially in the dose escalation phase and/or the regimen selection phase of the study will not be included in the primary analysis.
Following completion of the 2nd study period for Cohort 2, the safety data will be reviewed by the DSMB and in the absence of safety concerns the subjects may enter the 48 week treatment phase and receive 9 mg/kg PRO053 once weekly by SC injection. Three new subjects will enter cohort 2 (i.e. 6 subjects in total at this dose level).
After the initial 12 subjects have completed 12 weeks of dosing the dose for the Treatment group (30 new subjects) will be selected based on the totality of the 12-week data from those initial 12 subjects. The initial 12 subjects will also be dosed on the selected dose (i.e. continue on their dose or [down-]titrate). Receives: Drug: Treatment Phase Group 4 |
| Dosing extension | Experimental | All subjects who have completed the dose escalation and regimen selection phase of the study (N=15), and subjects who have complete the treatment phase of the study who have tolerated the treatment will be offered to continue dosing in the dosing extension with ongoing assessment of efficacy, safety, and tolerability of BMN 053. Safety, efficacy, PK/PD and biomarker assessments will be performed at scheduled visits; adverse events (AEs) and concomitant medications and therapies will be continuously monitored. The dose extension phase will provide BMN 053 treatment for 48 weeks. Receives: Drug: Dosing Extension |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in 6 minute walk test
Measured: after 48 weeks of treatment phase
Secondary outcomes (10)
Muscle function
Measured: after 48 weeks treatment phase
Muscle strength
Measured: after 48 weeks treatment phase
Pulmonary function
Measured: after 48 weeks treatment phase
Functional outcomes questionnaire
Measured: after 48 weeks treatment phase
Adverse Events
Measured: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase
Safety Laboratory
Measured: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase
Cardiac function
Measured: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase
Pharmacokinetic parameters at different dose levels
Measured: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase
Presence of (BMD-like) dystrophin expression in muscle biopsy
Measured: after 48 weeks treatment phase
Production of exon skip 53 mRNA in muscle biopsy
Measured: after 48 weeks treatment phase
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2013 (estimated)
- Study startJun 2013
- Primary completion3 Aug 2016
- Study completion3 Aug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Duchenne Muscular DystrophyStudies of the same condition, open and under way.
- More trials run by BioMarin PharmaceuticalThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioMarin Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- V. Straub, Prof., Principal investigator, Institute of Genetic Medicine, Newcastle University, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01957059
- Sponsor's protocol ID
- PRO053-CLIN-01
- Status last verified
- Dec 2017
- First submitted
- 2 Jul 2013
- Last updated
- 8 Dec 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Open-label, Dose Escalating With 48 Week Treatment Study to Assess the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of BMN053 (Previously Known as PRO053) in Subjects With Duchenne Muscular Dystrophy.
- ClinicalTrials.gov ID
- NCT01957059
- Acronym / sponsor ID
- PRO053-CLIN-01
- Conditions
- Duchenne Muscular Dystrophy
- Keywords
- DMD, Duchenne muscular dystrophy, Duchenne, BMN053, BioMarin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 9 participants (actual)
- Lead sponsor
- BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- Jun 2013 (actual)
- Primary completion
- 3 Aug 2016 (actual)
- Study completion
- 3 Aug 2016 (actual)
- First posted
- 8 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to see whether BMN053 is safe and effective to use as medication for Duchenne muscular dystrophy (DMD) patients with a mutation around location 53 in the DNA for the dystrophin protein.
Detailed description
A Phase I/II, open-label, dose escalating with 48-week treatment study to assess the safety and tolerability, pharmacokinetics, pharmacodynamics and efficacy of BMN 053 (previously known as PRO053) in subjects with Duchenne muscular dystrophy
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose escalation phase | Experimental | Drug: Regimen Selection Phase Group 1 (COMPLETED)In the dose-escalation phase, following screening assessment, two cohorts of three subjects each receive two single doses of BMN 053 in two study periods (i.e., four single doses in total per subject). In each study period they will receive BMN 053 by IV infusion and by SC injection (separated by one week). The proposed doses are 1 mg/kg (Cohort 1, study period 1), 3 mg/kg (Cohort 2, study period 1), 6 mg/kg (Cohort 1, study period 2) and 9 mg/kg (Cohort 2, study period 2). The actual doses may be amended or repeated based on emerging data from previous doses. |
| Regimen selection | Experimental | Drug: Regimen Selection Phase Group 2, Drug: Regimen Selection Phase Group 3After completion of the dose-escalation period of Cohort 1, the safety data of the subjects will be reviewed by a DSMB and if no safety concerns these subjects will continue to receive 6 mg/kg BMN053 weekly by SC injection for 48 weeks. 3 more treatment-naïve subjects will be entered into this Group. These 6 subjects will form Group 1 of the Regimen Selection phase who received 6 mg/kg SC. At the time of this amendment (4) this part of the study has been completed. Following completion of the dose-escalation study period of Cohort 2 (9 mg/kg), the planned review of the preliminary plasma PK data from the dose-escalation phase showed a relative bioavailability of 50% for BMN053 with SC dosing (50% lower plasma AUC after SC dosing compared to IV dosing). Taking into consideration the risk of injection site reactions noted with similar compounds when administered SC over longer term, the planned 9 mg/kg BMN053 weekly by SC injection will be discontinued to be replaced by an IV regimen. |
| 48-week Treatment Phase | Experimental | Drug: Treatment Phase Group 4Thirty additional treatment-naïve subjects will be recruited for the primary evaluation and will receive treatment at the recommended regimen for a total of 48 weeks. Subjects dosed initially in the dose escalation phase and/or the regimen selection phase of the study will not be included in the primary analysis. Following completion of the 2nd study period for Cohort 2, the safety data will be reviewed by the DSMB and in the absence of safety concerns the subjects may enter the 48 week treatment phase and receive 9 mg/kg PRO053 once weekly by SC injection. Three new subjects will enter cohort 2 (i.e. 6 subjects in total at this dose level). After the initial 12 subjects have completed 12 weeks of dosing the dose for the Treatment group (30 new subjects) will be selected based on the totality of the 12-week data from those initial 12 subjects. The initial 12 subjects will also be dosed on the selected dose (i.e. continue on their dose or [down-]titrate). |
| Dosing extension | Experimental | Drug: Dosing ExtensionAll subjects who have completed the dose escalation and regimen selection phase of the study (N=15), and subjects who have complete the treatment phase of the study who have tolerated the treatment will be offered to continue dosing in the dosing extension with ongoing assessment of efficacy, safety, and tolerability of BMN 053. Safety, efficacy, PK/PD and biomarker assessments will be performed at scheduled visits; adverse events (AEs) and concomitant medications and therapies will be continuously monitored. The dose extension phase will provide BMN 053 treatment for 48 weeks. |
Who may qualify
- Ages
- 5 to 18 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- Duchenne muscular dystrophy resulting from a mutation correctable by treatment with BMN053 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 HRMCA (High-Resolution Melting Curve Analysis).
- Ambulant boys aged at least 5 years on the day of first dosing able to walk for at least 300 metres in the 6 minute walking distance (6MWD) test. In addition, results of the 6MWD test must be within ±30 metres of each other at 2 of 3 pre-treatment visits (screen 1, 2 and baseline) prior to first BMN053 administration.
- Adequate quality for biopsy (confirmed with MRI) of the lateral head of the gastrocnemius muscle. Only under exceptional circumstances will an alternative muscle (preferably brachii) be considered for biopsy and only following discussion between the Principal Investigator and the BioMarin Medical Monitor.
- Life expectancy of at least 3 years after inclusion in the study.
- Glucocorticosteroid use which is stable for at least 3 months prior to first BMN053 administration. Subjects must have been receiving glucocorticosteroids for at least 6 months prior to the first BMN053 administration.
Key exclusion criteria (12 listed)
- Current or history of liver disease or impairment.
- Current or history of renal disease or impairment.
- At least two aPTT above upper limit of normal (ULN) within the last month prior to first dose of BMN053.
- Screening platelet count below the lower limit of normal (LLN).
- Acute illness within 4 weeks prior to first dose of BMN053 which may interfere with the study assessments.
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 |
|---|---|---|
| Regimen Selection Phase Group 2All doses of BMN053 will be administered as IV infusions. The proposed doses are as follows: • 3 mg/kg | Drug | Regimen selection |
| Regimen Selection Phase Group 3All doses of BMN053 will be administered as IV infusions. The proposed doses are as follows: • 4-6 mg/kg | Drug | Regimen selection |
| Treatment Phase Group 4All doses of PRO053 will be administered as IV infusions. The proposed doses will be decided upon completion of the Regimen Selection Phase of Groups 2 and 3 | Drug | 48-week Treatment Phase |
| Regimen Selection Phase Group 1 (COMPLETED)All doses of BMN053 have been administered as subcutaneous injections. | Drug | Dose escalation phase |
| Dosing ExtensionAll doses of PRO053 will be administered as IV infusions. The proposed doses will be decided upon completion of the Regimen Selection Phase of Groups 2 and 3 and the Treatment Phase Group 4. | Drug | Dosing extension |
Primary outcome
Change from baseline in 6 minute walk test
Time frame: after 48 weeks of treatment phase
10 secondary outcomes
Muscle function
Time frame: after 48 weeks treatment phase
Muscle strength
Time frame: after 48 weeks treatment phase
Pulmonary function
Time frame: after 48 weeks treatment phase
Functional outcomes questionnaire
Time frame: after 48 weeks treatment phase
Adverse Events
Time frame: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase
Safety Laboratory
Time frame: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase
Cardiac function
Time frame: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase
Pharmacokinetic parameters at different dose levels
Time frame: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase
Presence of (BMD-like) dystrophin expression in muscle biopsy
Time frame: after 48 weeks treatment phase
Production of exon skip 53 mRNA in muscle biopsy
Time frame: after 48 weeks treatment phase
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2017.
- BioMarin websiteLink provided by the sponsor.
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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.
V. Straub, Prof. principal investigator
Institute of Genetic Medicine, Newcastle University, UK
6 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Regimen Selection Phase Group 2, Regimen Selection Phase Group 3 and Treatment Phase Group 4 in people with Duchenne Muscular Dystrophy, run by BioMarin Pharmaceutical at 6 sites in 5 countries.
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 9 inclusion and 12 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: stopped early, as of the sponsor's last update on 8 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United Kingdom, Belgium, France, Italy, Netherlands. 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?
The study was stopped early. Results are not available in the source record.
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?
Change from baseline in 6 minute walk test (time frame: after 48 weeks of treatment phase). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Dec 2017.