Duchenne Muscular DystrophyPhase 1/2NCT01037309
Phase I/II Study of PRO044 in Duchenne Muscular Dystrophy (DMD)
A Phase 1/2 study testing PRO044 SC and PRO044 IV in people with Duchenne Muscular Dystrophy, run by BioMarin Pharmaceutical at 4 sites in 4 countries.
Trial summary
The purpose of this study is to see whether PRO044 is safe and effective to use as medication for DMD patients with a mutation around location 44 in the DNA for the dystrophin protein. Read more about this study
- Who is it for?
- Ages 5 to 16 years, men only
- Conditions the study is for
- Duchenne Muscular Dystrophy
- What is being tested?
- PRO044 SC and PRO044 IV
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 4 sitesin 4 countries
- Study dates
- Dec 2009to Oct 2013
- 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 16 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Boys aged between 5 and 16 years inclusive.
- Duchenne muscular dystrophy resulting from a mutation correctable by treatment with PRO044.
- Life expectancy of at least 6 months.
- No previous treatment with investigational medicinal treatment within 6 months prior to the start of the (pre)-screening for the study.
- No previous treatment with idebenone within 6 months prior to the start of the (pre)-screening for the study.
- 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 patient, according to the local regulations).
- Glucocorticosteroids use which is stable for at least 2 months prior first drug administration.
Who cannot join
- Aberrant RNA splicing and/or aberrant response to PRO044, detected by in vitro PRO044 assay during pre-screening.
- Known presence of dystrophin in ≥ 5% of fibers in a pre-study diagnostic muscle biopsy.
- Severe muscle abnormalities defined as increased signal intensity in >50% of the tibialis anterior muscle at MRI.
- FEV1 and/or FVC < 60% of predicted.
- Current or history of liver or renal disease.
- Acute illness within 4 weeks prior to treatment (Day 1) which may interfere with the measurements.
Show all 17Show fewer
- Severe mental retardation which in the opinion of the investigator prohibits participation in this study.
- Severe cardiac myopathy which in the opinion of the investigator prohibits participation in this study.
- Need for mechanical ventilation.
- Creatinine concentration above 1.5 times the upper limit of normal (age corrected).
- Serum ASAT and/or ALAT concentration(s) which suggest hepatic impairment.
- Use of anticoagulants, antithrombotics or antiplatelet agents.
- Use of idebenone.
- Use of any investigational product within 6 months prior to the start of the (pre)-screening for the study.
- Subject has donated blood less than 90 days before the start of the (pre)-screening for the study.
- Current or history of drug and/or alcohol abuse.
- Participation in another trial with an investigational product.
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
About this study
Official title: A Phase I/IIa, Open Label, Escalating Dose, Pilot Study to Assess the Effect, Safety, Tolerability and Pharmacokinetics of Multiple Subcutaneous and Intravenous Doses of PRO044 in Patients With Duchenne Muscular Dystrophy
The purpose of this study is to see whether PRO044 is safe and effective to use as medication for DMD patients with a mutation around location 44 in the DNA for the dystrophin protein.
Read the detailed description
To assess the effect of PRO044 at different dose levels in subjects with Duchenne muscular dystrophy To assess the safety and tolerability of PRO044 at different dose levels in subjects with Duchenne muscular dystrophy To determine the pharmacokinetics of PRO044 at different dose levels after subcutaneous and intravenous administration in subjects with Duchenne muscular dystrophy.
- Conditions
- Duchenne Muscular Dystrophy
- Being tested
- PRO044 SC, PRO044 IV
- 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.
PRO044 SCDrug
Subcutaneous injection, once a week, for five weeks
PRO044 IVDrug
Intravenous injection, once a week, for five weeks
| Study group | Role | What they receive |
|---|---|---|
| PRO044, cohort 1 | Experimental | Subcutaneous injection of 0.5 mg/kg on day 1, 8, 15, 22 and 29. Receives: Drug: PRO044 SC |
| PRO044, cohort 2 | Experimental | Subcutaneous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29. Receives: Drug: PRO044 SC |
| PRO044, cohort 3 | Experimental | Subcutaneous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29. Receives: Drug: PRO044 SC |
| PRO044, cohort 4 | Experimental | Subcutaneous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29. Receives: Drug: PRO044 SC |
| PRO044, cohort 5 | Experimental | Subcutaneous injection of maximally 10 mg/kg on day 1, 8, 15, 22 and 29 Receives: Drug: PRO044 SC |
| PRO044, cohort 6 | Experimental | Subcutaneous injection of maximally 12 mg/kg on day 1, 8, 15, 22 and 29 Receives: Drug: PRO044 SC |
| PRO044, cohort 7 | Experimental | Intravenous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29 Receives: Drug: PRO044 IV |
| PRO044, cohort 8 | Experimental | Intravenous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29 Receives: Drug: PRO044 IV |
| PRO044, cohort 9 | Experimental | Intravenous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29 Receives: Drug: PRO044 IV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Increase in Dystrophin Expression in the Muscle Biopsies by Immunofluorescence Analyses of Cross-sections and by Western Blot Analyses of Total Protein Extracts
Measured: Within 13 weeks after 5 weeks of treatment
Safety and Tolerability of PRO044
number of subjects with 1 or more treatment emergent adverse events following SC or IV PRO044
Measured: During the 5 weeks of treatment and during the 13 weeks after treatment
Secondary outcomes (1)
PRO044 Pharmacokinetic Cmax (μg/mL) Following Subcutaneous Administration
Pharmacokinetic population evaluated for maximum plasma concentration (Cmax)
Measured: Week 1, Week 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2009 (estimated)
- Study startDec 2009
- Primary completionMay 2013
- Study completionOct 2013
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.
- 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
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioMarin Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- A. Ferlini, PhD, Principal investigator, Università di Ferrara and S.Anna Hospital, Ferrara, ItalyJ. J. Verschuuren, MD, Principal investigator, Leiden University Medical Center, Leiden, the NetherlandsN. Goemans, MD, Principal investigator, UZ Leuven, Leuven, BelgiumM. Tulinius, MD, Principal investigator, The Queen Silvia Children's Hospital, Gothenburg, Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01037309
- Sponsor's protocol ID
- PRO044-CLIN-01
- Status last verified
- Sep 2018
- First submitted
- 21 Dec 2009
- Last updated
- 16 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIa, Open Label, Escalating Dose, Pilot Study to Assess the Effect, Safety, Tolerability and Pharmacokinetics of Multiple Subcutaneous and Intravenous Doses of PRO044 in Patients With Duchenne Muscular Dystrophy
- ClinicalTrials.gov ID
- NCT01037309
- Acronym / sponsor ID
- PRO044-CLIN-01
- Conditions
- Duchenne Muscular Dystrophy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- Dec 2009
- Primary completion
- May 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 23 Dec 2009 (estimated)
- Results
- Posted 9 Apr 2015
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 this study is to see whether PRO044 is safe and effective to use as medication for DMD patients with a mutation around location 44 in the DNA for the dystrophin protein.
Detailed description
To assess the effect of PRO044 at different dose levels in subjects with Duchenne muscular dystrophy To assess the safety and tolerability of PRO044 at different dose levels in subjects with Duchenne muscular dystrophy To determine the pharmacokinetics of PRO044 at different dose levels after subcutaneous and intravenous administration 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
- 9
| Arm | Type | Receives |
|---|---|---|
| PRO044, cohort 1 | Experimental | Drug: PRO044 SCSubcutaneous injection of 0.5 mg/kg on day 1, 8, 15, 22 and 29. |
| PRO044, cohort 2 | Experimental | Drug: PRO044 SCSubcutaneous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29. |
| PRO044, cohort 3 | Experimental | Drug: PRO044 SCSubcutaneous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29. |
| PRO044, cohort 4 | Experimental | Drug: PRO044 SCSubcutaneous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29. |
| PRO044, cohort 5 | Experimental | Drug: PRO044 SCSubcutaneous injection of maximally 10 mg/kg on day 1, 8, 15, 22 and 29 |
| PRO044, cohort 6 | Experimental | Drug: PRO044 SCSubcutaneous injection of maximally 12 mg/kg on day 1, 8, 15, 22 and 29 |
| PRO044, cohort 7 | Experimental | Drug: PRO044 IVIntravenous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29 |
| PRO044, cohort 8 | Experimental | Drug: PRO044 IVIntravenous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29 |
| PRO044, cohort 9 | Experimental | Drug: PRO044 IVIntravenous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29 |
Who may qualify
- Ages
- 5 to 16 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Boys aged between 5 and 16 years inclusive.
- Duchenne muscular dystrophy resulting from a mutation correctable by treatment with PRO044.
- Life expectancy of at least 6 months.
- No previous treatment with investigational medicinal treatment within 6 months prior to the start of the (pre)-screening for the study.
- No previous treatment with idebenone within 6 months prior to the start of the (pre)-screening for the study.
Key exclusion criteria (17 listed)
- Aberrant RNA splicing and/or aberrant response to PRO044, detected by in vitro PRO044 assay during pre-screening.
- Known presence of dystrophin in ≥ 5% of fibers in a pre-study diagnostic muscle biopsy.
- Severe muscle abnormalities defined as increased signal intensity in >50% of the tibialis anterior muscle at MRI.
- FEV1 and/or FVC < 60% of predicted.
- Current or history of liver or renal disease.
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 |
|---|---|---|
| PRO044 SCSubcutaneous injection, once a week, for five weeks | Drug | PRO044, cohort 1, PRO044, cohort 2, PRO044, cohort 3, PRO044, cohort 4, PRO044, cohort 5, PRO044, cohort 6 |
| PRO044 IVIntravenous injection, once a week, for five weeks | Drug | PRO044, cohort 7, PRO044, cohort 8, PRO044, cohort 9 |
Primary outcome
Increase in Dystrophin Expression in the Muscle Biopsies by Immunofluorescence Analyses of Cross-sections and by Western Blot Analyses of Total Protein Extracts
Time frame: Within 13 weeks after 5 weeks of treatment
Safety and Tolerability of PRO044
Time frame: During the 5 weeks of treatment and during the 13 weeks after treatment
number of subjects with 1 or more treatment emergent adverse events following SC or IV PRO044
1 secondary outcome
PRO044 Pharmacokinetic Cmax (μg/mL) Following Subcutaneous Administration
Time frame: Week 1, Week 5
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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.
A. Ferlini, PhD principal investigator
Università di Ferrara and S.Anna Hospital, Ferrara, Italy
J. J. Verschuuren, MD principal investigator
Leiden University Medical Center, Leiden, the Netherlands
N. Goemans, MD principal investigator
UZ Leuven, Leuven, Belgium
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PRO044 SC and PRO044 IV in people with Duchenne Muscular Dystrophy, run by BioMarin Pharmaceutical at 4 sites in 4 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 17 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 16 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Belgium, Italy, Netherlands, Sweden. 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 9 Apr 2015). 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?
Increase in Dystrophin Expression in the Muscle Biopsies by Immunofluorescence Analyses of Cross-sections and by Western Blot Analyses of Total Protein Extracts (time frame: Within 13 weeks after 5 weeks of treatment). The study lists 2 primary outcomes in all. 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 16 Oct 2018.