Muscular DystrophiesPhase 2NCT01910649
A Phase I/II, Open Label, Escalating Dose, Pilot Study to Assess Effect, Safety, Tolerability and PK of Multiple SC Doses of Drisapersen in Patients With Duchenne Muscular Dystrophy and to Assess the Potential for IV Dosing as an Alternative Route of Administration
A Phase 2 study testing Drisapersen in people with Muscular Dystrophies, run by BioMarin Pharmaceutical.
Trial summary
The purpose of the extension phase of this study is to determine whether Drisapersen is effective in the treatment of boys with Duchenne muscular dystrophy resulting from a mutation thought to be corrected by exon 51 skipping. Read more about this study
- Who is it for?
- Ages 5 to 16 years, men only
- Conditions the study is for
- Muscular Dystrophies
- What is being tested?
- Drisapersen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- No sites listed yet
- Study dates
- Mar 2008to Sep 2016
- Phase
- Phase 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 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 PRO051.
- Not ventilator dependent.
- Life expectancy of at least six months.
- No previous treatment with investigational medicinal treatment within six months prior to the study.
- Willing and able to adhere to the study visit schedule and other protocol requirements.
Who cannot join
- Aberrant RNA splicing and/or aberrant response to PRO051, detected by in vitro PRO051 assay during 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.
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- 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.
- Subject has donated blood less than 90 days before the start of the study.
- Current or history of drug and/or alcohol abuse.
- Participation in another trial with an investigational product.
About this study
Official title: A Phase I/II, Open Label, Escalating Dose, Pilot Study to Assess the Effect, Safety, Tolerability and Pharmacokinetics of Multiple Subcutaneous Doses of Drisapersen in Patients With Duchenne Muscular Dystrophy and to Assess the Potential for Intravenous Dosing as an Alternative Route of Administration
The purpose of the extension phase of this study is to determine whether Drisapersen is effective in the treatment of boys with Duchenne muscular dystrophy resulting from a mutation thought to be corrected by exon 51 skipping.
- Conditions
- Muscular Dystrophies
- Being tested
- Drisapersen
- Keywords
- drisapersen
- Medical subject headings
- Muscular Dystrophies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DrisapersenDrug
Also called PRO051
Subcutaneous and Intravenous
| Study group | Role | What they receive |
|---|---|---|
| Drisapersen | Experimental | Extension phase of treatment. Intravenous dosing of drisapersen will be investigated as an alternative route of administration Receives: Drug: Drisapersen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute phase: Safety data
Summarized per dose group
Measured: 18 weeks
Acute phase and Continued Treatment Phase : Pharmacokinetics measured by T1/2, Cmax, Ctrough, 7d, tmax, and volume of distribution and clearance
Plasma concentration versus time profiles of PRO051 (GSK2402968)
Measured: 18 weeks
Acute phase and Continued Treatment Phase : Safety as assessed by the collection of adverse events (AEs)
Change from baseline and summarized values
Measured: 72 weeks
Continued Treatment Phase :Safety as assessed by laboratory parameters
Change from baseline and summarized values
Measured: 72 weeks
Secondary outcomes (8)
Acute phase: Production of exon skip 51 messenger Ribonucleic acid (mRNA)
Measured: 18 weeks
Acute phase: Presence of dystrophin expression
Measured: 18 weeks
Acute phase: Muscle function
Timed tests and 6-minutes walk
Measured: 18 weeks
Acute phase: Muscle strength
Quantitative Muscle Testing [QMT]- Cooperative International Neuromuscular Research Group (CINRG) and Manual Muscle Testing [MMT]
Measured: 18 weeks
Continued Treatment Phase: Exon skip efficiency
Measured: 72 weeks
Continued Treatment Phase Dystrophin expression in muscle biopsy
Measured: 72 weeks
Continued Treatment Phase: Muscle function
Timed tests and 6-minutes walk
Measured: 300 weeks
Continued Treatment Phase: Muscle strength
Handheld myometry and spirometry
Measured: 300 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2013 (estimated)
- Study startMar 2008
- Primary completionSep 2016
- Study completionSep 2016
Why it stopped: Regulatory approval was not obtained for drisapersen, hence BioMarin is stopping the development of all exon skipping oligonucleotides in DMD.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Muscular DystrophiesStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioMarin Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- N Goemans, Dr., Principal investigator, UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01910649
- Sponsor's protocol ID
- 114673
- Other IDs
- 2007-004819-54
- Status last verified
- Nov 2016
- First submitted
- 2 Aug 2012
- Last updated
- 7 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Goemans NM, Tulinius M, van den Akker JT, Burm BE, Ekhart PF, Heuvelmans N, Holling T, Janson AA, Platenburg GJ, Sipkens JA, Sitsen JM, Aartsma-Rus A, van Ommen GJ, Buyse G, Darin N, Verschuuren JJ, Campion GV, de Kimpe SJ, van Deutekom JC. Systemic administration of PRO051 in Duchenne's muscular dystrophy. N Engl J Med. 2011 Apr 21;364(16):1513-22. doi: 10.1056/NEJMoa1011367. Epub 2011 Mar 23.
PubMed 21428760Goemans NM, Tulinius M, van den Hauwe M, Kroksmark AK, Buyse G, Wilson RJ, van Deutekom JC, de Kimpe SJ, Lourbakos A, Campion G. Long-Term Efficacy, Safety, and Pharmacokinetics of Drisapersen in Duchenne Muscular Dystrophy: Results from an Open-Label Extension Study. PLoS One. 2016 Sep 2;11(9):e0161955. doi: 10.1371/journal.pone.0161955. eCollection 2016.
PubMed 27588424
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Open Label, Escalating Dose, Pilot Study to Assess the Effect, Safety, Tolerability and Pharmacokinetics of Multiple Subcutaneous Doses of Drisapersen in Patients With Duchenne Muscular Dystrophy and to Assess the Potential for Intravenous Dosing as an Alternative Route of Administration
- ClinicalTrials.gov ID
- NCT01910649
- Acronym / sponsor ID
- 114673
- Conditions
- Muscular Dystrophies
- Keywords
- drisapersen
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Regulatory approval was not obtained for drisapersen, hence BioMarin is stopping the development of all exon skipping oligonucleotides in DMD.
- Enrolment
- 12 participants (actual)
- Lead sponsor
- BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- Mar 2008
- Primary completion
- Sep 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 29 Jul 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 extension phase of this study is to determine whether Drisapersen is effective in the treatment of boys with Duchenne muscular dystrophy resulting from a mutation thought to be corrected by exon 51 skipping.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Drisapersen | Experimental | Drug: DrisapersenExtension phase of treatment. Intravenous dosing of drisapersen will be investigated as an alternative route of administration |
Who may qualify
- Ages
- 5 to 16 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Boys aged between 5 and 16 years inclusive.
- Duchenne muscular dystrophy resulting from a mutation correctable by treatment with PRO051.
- Not ventilator dependent.
- Life expectancy of at least six months.
- No previous treatment with investigational medicinal treatment within six months prior to the study.
Key exclusion criteria (15 listed)
- Aberrant RNA splicing and/or aberrant response to PRO051, detected by in vitro PRO051 assay during 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 |
|---|---|---|
| DrisapersenAlso: PRO051Subcutaneous and Intravenous | Drug | Drisapersen |
Primary outcome
Acute phase: Safety data
Time frame: 18 weeks
Summarized per dose group
Acute phase and Continued Treatment Phase : Pharmacokinetics measured by T1/2, Cmax, Ctrough, 7d, tmax, and volume of distribution and clearance
Time frame: 18 weeks
Plasma concentration versus time profiles of PRO051 (GSK2402968)
Acute phase and Continued Treatment Phase : Safety as assessed by the collection of adverse events (AEs)
Time frame: 72 weeks
Change from baseline and summarized values
Continued Treatment Phase :Safety as assessed by laboratory parameters
Time frame: 72 weeks
Change from baseline and summarized values
8 secondary outcomes
Acute phase: Production of exon skip 51 messenger Ribonucleic acid (mRNA)
Time frame: 18 weeks
Acute phase: Presence of dystrophin expression
Time frame: 18 weeks
Acute phase: Muscle function
Time frame: 18 weeks
Acute phase: Muscle strength
Time frame: 18 weeks
Continued Treatment Phase: Exon skip efficiency
Time frame: 72 weeks
Continued Treatment Phase Dystrophin expression in muscle biopsy
Time frame: 72 weeks
Continued Treatment Phase: Muscle function
Time frame: 300 weeks
Continued Treatment Phase: Muscle strength
Time frame: 300 weeks
Results and safety
The study was stopped early (reason given: Regulatory approval was not obtained for drisapersen, hence BioMarin is stopping the development of all exon skipping oligonucleotides in DMD.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2016.
- Results publication: PubMed 21428760Goemans NM, Tulinius M, van den Akker JT, Burm BE, Ekhart PF, Heuvelmans N, Holling T, Janson AA, Platenburg GJ, Sipkens JA, Sitsen JM, Aartsma-Rus A, van Ommen GJ, Buyse G, Darin N, Verschuuren JJ, Campion GV, de Kimpe SJ, van Deutekom JC. Systemic administration of PRO051 in Duchenne's muscular dystrophy. N Engl J Med. 2011 Apr 21;364(16):1513-22. doi: 10.1056/NEJMoa1011367. Epub 2011 Mar 23.
- Derived from this study: PubMed 27588424Goemans NM, Tulinius M, van den Hauwe M, Kroksmark AK, Buyse G, Wilson RJ, van Deutekom JC, de Kimpe SJ, Lourbakos A, Campion G. Long-Term Efficacy, Safety, and Pharmacokinetics of Drisapersen in Duchenne Muscular Dystrophy: Results from an Open-Label Extension Study. PLoS One. 2016 Sep 2;11(9):e0161955. doi: 10.1371/journal.pone.0161955. eCollection 2016.
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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.
N Goemans, Dr. principal investigator
UZ Leuven
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Drisapersen in people with Muscular Dystrophies, run by BioMarin Pharmaceutical.
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 6 inclusion and 15 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 7 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
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 phase mean?
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 (reason given: Regulatory approval was not obtained for drisapersen, hence BioMarin is stopping the development of all exon skipping oligonucleotides in DMD.). 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?
Acute phase: Safety data (time frame: 18 weeks). The study lists 4 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 NCT01910649, which also lists 2 linked publications.
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 Nov 2016.