Duchenne Muscular DystrophyPhase 1/2NCT01826474
Phase IIb Study of PRO045 in Subjects With Duchenne Muscular Dystrophy
A Phase 1/2 study testing PRO045, 0.15 mg/kg/week, PRO045, 1.0 mg/kg/week and PRO045, 3.0 mg/kg/week 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 PRO045 is safe and effective to use as medication for Duchenne Muscular Dystrophy (DMD) patients with a mutation around location 45 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?
- PRO045, 0.15 mg/kg/week, PRO045, 1.0 mg/kg/week and PRO045, 3.0 mg/kg/week
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 6 sitesin 5 countries
- Study dates
- Jan 2013to 31 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 PRO045 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), and correctable by PRO045-induced DMD exon 45 skipping in cultured skin-derived myo-converted fibroblasts.
- Ambulant boys aged at least 5 years on the day of first dosing able to walk for at least 230 meters in the 6 minute walking distance (6MWD) test at first screening visit and also at the baseline visit. In addition, 2 of the 3 pre-treatment 6MWD tests (screen 1, screen 2, baseline) must be within +/-30 metres of each other prior to first PRO045 administration.
- Adequate quality for biopsy (confirmed with MRI) of the lateral head of the gastrocnemius muscle. An alternative muscle may be considered for biopsy but only following discussion between the Principal Investigator and the Prosensa 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 PRO045 administration. Subjects must have been receiving glucocorticosteroids for at least 6 months prior to the first PRO045 administration.
- Willing and able to adhere to the study visit schedule and other protocol requirements.
- 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.
Who cannot join
- Known presence of dystrophin in ≥5% of fibres in a pre-study diagnostic muscle biopsy (i.e. historic muscle biopsy taken prior to written informed consent for this study).
- Current or history of liver disease or impairment.
- Current or history of renal disease or impairment.
- At least two aPTT above ULN within the last month.
- Screening platelet count below the lower limit of normal (LLN).
- Acute illness within 4 weeks prior to first dose of PRO045 which may interfere with the study assessments.
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- Severe mental retardation or behavioural problems which in the opinion of the investigator prohibits participation in this study.
- 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 of the study.
- 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
Institute of Genetic Medicine International Centre for Life
Newcastle
About this study
Official title: A Phase IIb, Open-label Study to Assess the Efficacy, Safety, Pharmacodynamics and Pharmacokinetics of Multiple Subcutaneous Doses of PRO045 in Subjects With Duchenne Muscular Dystrophy
The purpose of the study is to see whether PRO045 is safe and effective to use as medication for Duchenne Muscular Dystrophy (DMD) patients with a mutation around location 45 in the DNA for the dystrophin protein.
Read the detailed description
A phase IIb, open-label, multiple-dose study. The study consists of two phases; a dose escalation phase (with subsequent dose-titration) and a 48-week treatment phase.
- Conditions
- Duchenne Muscular Dystrophy
- Being tested
- PRO045, 0.15 mg/kg/week, PRO045, 1.0 mg/kg/week, PRO045, 3.0 mg/kg/week, PRO045, 6.0 mg/kg/week, PRO045, 9.0 mg/kg/week
- Keywords
- Duchenne muscular dystrophy, DMD, Prosensa, Duchenne
- 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.
PRO045, 0.15 mg/kg/weekDrug
Subcutaneous injection
PRO045, 1.0 mg/kg/weekDrug
Subcutaneous injection
PRO045, 3.0 mg/kg/weekDrug
Subcutaneous injection
PRO045, 6.0 mg/kg/weekDrug
Subcutaneous injection
PRO045, 9.0 mg/kg/weekDrug
Subcutaneous injection
PRO045, selected doseDrug
Subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| PRO045, cohort 1 | Experimental | 0.15 mg/kg until dose-titration Receives: Drug: PRO045, 0.15 mg/kg/week |
| PRO045, cohort 2 | Experimental | 1.0 mg/kg until dose-titration Receives: Drug: PRO045, 1.0 mg/kg/week |
| PRO045, cohort 3 | Experimental | 3.0 mg/kg until dose-titration Receives: Drug: PRO045, 3.0 mg/kg/week |
| PRO045, cohort 4 | Experimental | 6.0 mg/kg until dose-titration Receives: Drug: PRO045, 6.0 mg/kg/week |
| PRO045, cohort 5 | Experimental | 9.0 mg/kg until move to 48 week treatment phase Receives: Drug: PRO045, 9.0 mg/kg/week |
| PRO045, cohort 6 | Experimental | 48 week treatment phase Receives: Drug: PRO045, selected dose |
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 (5)
Muscle function
Measured: after 48 weeks of treatment phase
Muscle strength
Measured: after 48 weeks treatment phase
Performance of upper limb
Measured: after 48 weeks of treatment phase
Functional outcomes questionnaire
Measured: after 48 weeks of treatment
Safety
Measured: after 48 weeks of 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 Apr 2013 (estimated)
- Study startJan 2013
- Primary completion31 Aug 2016
- Study completion31 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
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioMarin Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- T. Voit, MD PhD, Principal investigator, Institut de Myologie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01826474
- Sponsor's protocol ID
- PRO045-CLIN-01
- Status last verified
- Dec 2017
- First submitted
- 20 Mar 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 IIb, Open-label Study to Assess the Efficacy, Safety, Pharmacodynamics and Pharmacokinetics of Multiple Subcutaneous Doses of PRO045 in Subjects With Duchenne Muscular Dystrophy
- ClinicalTrials.gov ID
- NCT01826474
- Acronym / sponsor ID
- PRO045-CLIN-01
- Conditions
- Duchenne Muscular Dystrophy
- Keywords
- Duchenne muscular dystrophy, DMD, Prosensa, Duchenne
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 15 participants (actual)
- Lead sponsor
- BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- Jan 2013 (actual)
- Primary completion
- 31 Aug 2016 (actual)
- Study completion
- 31 Aug 2016 (actual)
- First posted
- 8 Apr 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 PRO045 is safe and effective to use as medication for Duchenne Muscular Dystrophy (DMD) patients with a mutation around location 45 in the DNA for the dystrophin protein.
Detailed description
A phase IIb, open-label, multiple-dose study. The study consists of two phases; a dose escalation phase (with subsequent dose-titration) and a 48-week treatment phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| PRO045, cohort 1 | Experimental | Drug: PRO045, 0.15 mg/kg/week0.15 mg/kg until dose-titration |
| PRO045, cohort 2 | Experimental | Drug: PRO045, 1.0 mg/kg/week1.0 mg/kg until dose-titration |
| PRO045, cohort 3 | Experimental | Drug: PRO045, 3.0 mg/kg/week3.0 mg/kg until dose-titration |
| PRO045, cohort 4 | Experimental | Drug: PRO045, 6.0 mg/kg/week6.0 mg/kg until dose-titration |
| PRO045, cohort 5 | Experimental | Drug: PRO045, 9.0 mg/kg/week9.0 mg/kg until move to 48 week treatment phase |
| PRO045, cohort 6 | Experimental | Drug: PRO045, selected dose48 week treatment phase |
Who may qualify
- Ages
- 5 to 18 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Duchenne muscular dystrophy resulting from a mutation correctable by treatment with PRO045 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), and correctable by PRO045-induced DMD exon 45 skipping in cultured skin-derived myo-converted fibroblasts.
- Ambulant boys aged at least 5 years on the day of first dosing able to walk for at least 230 meters in the 6 minute walking distance (6MWD) test at first screening visit and also at the baseline visit. In addition, 2 of the 3 pre-treatment 6MWD tests (screen 1, screen 2, baseline) must be within +/-30 metres of each other prior to first PRO045 administration.
- Adequate quality for biopsy (confirmed with MRI) of the lateral head of the gastrocnemius muscle. An alternative muscle may be considered for biopsy but only following discussion between the Principal Investigator and the Prosensa 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 PRO045 administration. Subjects must have been receiving glucocorticosteroids for at least 6 months prior to the first PRO045 administration.
Key exclusion criteria (13 listed)
- Known presence of dystrophin in ≥5% of fibres in a pre-study diagnostic muscle biopsy (i.e. historic muscle biopsy taken prior to written informed consent for this study).
- Current or history of liver disease or impairment.
- Current or history of renal disease or impairment.
- At least two aPTT above ULN within the last month.
- Screening platelet count below the lower limit of normal (LLN).
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 |
|---|---|---|
| PRO045, 0.15 mg/kg/weekSubcutaneous injection | Drug | PRO045, cohort 1 |
| PRO045, 1.0 mg/kg/weekSubcutaneous injection | Drug | PRO045, cohort 2 |
| PRO045, 3.0 mg/kg/weekSubcutaneous injection | Drug | PRO045, cohort 3 |
| PRO045, 6.0 mg/kg/weekSubcutaneous injection | Drug | PRO045, cohort 4 |
| PRO045, 9.0 mg/kg/weekSubcutaneous injection | Drug | PRO045, cohort 5 |
| PRO045, selected doseSubcutaneous injection | Drug | PRO045, cohort 6 |
Primary outcome
Change from baseline in 6 minute walk test
Time frame: after 48 weeks of treatment phase
5 secondary outcomes
Muscle function
Time frame: after 48 weeks of treatment phase
Muscle strength
Time frame: after 48 weeks treatment phase
Performance of upper limb
Time frame: after 48 weeks of treatment phase
Functional outcomes questionnaire
Time frame: after 48 weeks of treatment
Safety
Time frame: after 48 weeks of 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.
T. Voit, MD PhD principal investigator
Institut de Myologie
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 PRO045, 0.15 mg/kg/week, PRO045, 1.0 mg/kg/week and PRO045, 3.0 mg/kg/week 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 8 inclusion and 13 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.