Muscular Dystrophy, DuchennePhase 1RIM4DMDNCT02710591
Rimeporide in Patients With Duchenne Muscular Dystrophy
A Phase 1 study testing Rimeporide in people with Muscular Dystrophy, Duchenne, run by EspeRare Foundation at 4 sites in 4 countries.
Trial summary
In Duchenne Muscular Dystrophy (DMD) there is an imbalance between the levels of calcium and sodium in the muscles cells which is thought to be important in the damage which occurs overtime. Read more about this study
- Who is it for?
- Ages 6 to 14 years, men only
- Conditions the study is for
- Muscular Dystrophy, Duchenne
- What is being tested?
- Rimeporide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 4 sitesin 4 countries
- Study dates
- Mar 2016to Feb 2018
- Phase
- Phase 1
- 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 6 to 14 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Duchenne muscular dystrophy genetically confirmed;
- Males between 6 and 14 years old;
- Able to walk independently at least 75 meters;
- Patients on a stable dose of corticosteroids at least 6 months prior to baseline;
- Patients able to swallow capsules size 4 according to the parents and investigator opinion;
- Willing and able to comply with all protocol requirements and procedures;
- Signed informed consents by the parent(s)/legal guardian(s);
- France only: Affiliated to or a beneficiary of a social security system
Who cannot join
- Patients with significant renal disease or impairment, with Glomerular Filtration Rate estimated using plasma cystatin C level using the Filler formula less than 90ml/min/1.73m2
- Current or history of liver disease or impairment,
- History of any significant medical disorder which may confound the interpretation of either efficacy or safety data e.g. inflammatory, coagulation disease, unstable cardiac or respiratory disease
- Acute illness within 4 weeks of the first administration of study medication which may interfere with study assessments;
- Significant change of dosage and/or dosing regimens for corticosteroids planned for the duration of study medication;
- Use of beta blockers / and ACEI or ARB unless at stable dose for at least 3 months prior to baseline;
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- Use of Proton Pump Inhibitors unless at a stable dose for at least 3 months prior to baseline
- Use of aldosterone antagonists (i.e. spironolactone, eplerenone) within 3 months prior to first administration of study medication;
- Use of anticoagulants, antithrombotics or antiplatelet agents,
- Use of antibiotics with predominant renal secretion (e.g., cephalosporins), immunosuppressive agents exception corticosteroids, continuous treatment with non-steroidal, anti-inflammatory drugs (NSAIDs), or lithium;
- Previous treatment with idebenone or other forms of Coenzyme Q10 within 1 month of the first administration of study medication;
- Previous treatment with investigational drugs within 4 weeks (or 7 half-life if longer than 4 weeks) of the first administration of study medication including placebo;
- A baseline QTc>450msec,or history of risk factors for torsades de pointes (eg, heart failure, hypokalaemia, family history of long QT syndrome);
- LVEF≤ 45% at screening or within the past 6 months and/or history of acute heart failure;
- Ventilator dependent;
- Known individual hypersensitivity to any of the ingredients/excipients of the study medication;
- Patients with specific contraindication to MRI (e.g.: metallic foreign body, claustrophobia, etc.).
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
France1 site
I-Motion - Hôpital Armand Trousseau
Paris, Île-de-France Region, 75012
United Kingdom1 site
UCL Institute of Child Health and Great Ormond Street Hospital
London, WC1N 1EH
About this study
Official title: A Phase Ib, Open Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Oral Doses of Rimeporide in Patients With Duchenne Muscular Dystrophy
In Duchenne Muscular Dystrophy (DMD) there is an imbalance between the levels of calcium and sodium in the muscles cells which is thought to be important in the damage which occurs overtime. Sodium/proton type 1 exchanger (NHE-1) inhibition is an innovative pathway that has proved to efficiently prevent the accumulation of muscle damage (inflammation and fibrosis) in animal models of muscular dystrophies and heart failure. Based on prior safety and efficacy results in animal and humans, NHE-1 inhibition with Rimeporide represents a new therapeutic approach with no restriction on age and on genetic subtypes which could be combined to other treatments that restore or augment dystrophin.This study examines the safety and tolerability and effects on the muscles of rimeporide, in patients aged 6 to 14 years with Duchenne Muscular Dystrophy (DMD).
Read the detailed description
This study is designed as a phase Ib, multicenter, european, open label study to evaluate the safety and tolerability and biomarkers of a new drug, rimeporide, in boys aged 6 to 14 years with Duchenne Muscular Dystrophy (DMD).
Rimeporide will be taken orally for 4 weeks, three times a day. Dose will be adapted to body weight. The study will enrol 20 patients with DMD, aged 6 to 14 years. 4 dose levels will be tested, in 4 different cohorts with 5 patients taking the drug at each dose level.
During the study, there will be 6 visits in the Hospital over a maximum of 10 weeks. At each visit, patients will undergo safety examinations including vital signs, physical and neurological examinations, ECG, safety and hematology, biochemistry and urinalysis, concomitant treatments review, and any symptoms and side effects review. In addition, blood samples will be withdrawn for the evaluation of Rimeporide in plasma. Finally, additional blood \& urine samples will be collected to explore efficacy markers. Patients will also undergo 2 NMR (at screening and End of study) to develop non invasive biomarkers for further investigations in DMD patients.
The decision to progress to the next higher dose will be made after safety and tolerability data are reviewed for the preceding dose for 5 patients by SMC and determined that it is safe to proceed to the next dose level.
- Conditions
- Muscular Dystrophy, Duchenne
- Being tested
- Rimeporide
- Keywords
- Rimeporide
- 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.
RimeporideDrug
Also called EMD 87580
Cohort 1:
50 mg TID in patients with a body weight ≤ 30kg at Baseline and 75 mg TID in patients with a body weight > 30kg at Baseline
Cohort 2:
100mg TID in patients with a body weight ≤ 30kg at baseline and 150 mg TID in patients with a body weight > 30kg at Baseline
Cohort 3:
150 mg TID in patients with a body weight ≤ 30kg at baseline and 200 mg TID in patients with a body weight > 30kg at Baseline
Cohort 4:
200 mg TID in patients with a body weight ≤ 30kg at Baseline and 300 mg TID mg TID in patients with a body weight > 30kg at Baseline
| Study group | Role | What they receive |
|---|---|---|
| Rimeporide | Experimental | Multiple oral doses of rimeporide ranging from 50 to 300 mg will be administered three times a day (TID) for a total of 4 weeks. 4 ascending dose levels will be studied sequentially in ascending order. Rimeporide is provided as hard gel 25 mg or 50 mg capsules.
Each patient will participate in only 1 dose cohort. 5 patients are expected to be recruited in each cohort through all participating sites. Receives: Drug: Rimeporide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
Observations are given for the safety population (all patients who received at least one dose of study drug). Categorical data are presented with the number of subjects with at least one event for the following selections:
- treatment-emergent AEs (TEAEs)
- study drug-related TEAEs (ADRs)
- serious TEAEs
- study drug-related serious TEAEs (serious ADRs)
- TEAEs leading to withdrawal
- study drug-related TEAEs (ADRs) leading to withdrawal
- serious TEAEs leading to withdrawal
- TEAEs leading to death as outcome
Measured: up to 6 weeks from first administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2016 (estimated)
- Study startMar 2016
- Primary completionDec 2017
- Study completionFeb 2018
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 Muscular Dystrophy, DuchenneStudies 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
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- EspeRare Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Florence Porte-Thomé, Study director, R&D Director EspeRare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02710591
- Sponsor's protocol ID
- EspeRare_RIM_001
- Other IDs
- 2015-002530-50, 2015
- Acronym
- RIM4DMD
- Status last verified
- Jan 2019
- First submitted
- 26 Jan 2016
- Last updated
- 18 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib, Open Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Oral Doses of Rimeporide in Patients With Duchenne Muscular Dystrophy
- ClinicalTrials.gov ID
- NCT02710591
- Acronym / sponsor ID
- RIM4DMD / EspeRare_RIM_001
- Conditions
- Muscular Dystrophy, Duchenne
- Keywords
- Rimeporide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- EspeRare FoundationUniversity, hospital or other
- Study start
- Mar 2016
- Primary completion
- Dec 2017 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 17 Mar 2016 (estimated)
- Results
- Posted 18 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In Duchenne Muscular Dystrophy (DMD) there is an imbalance between the levels of calcium and sodium in the muscles cells which is thought to be important in the damage which occurs overtime. Sodium/proton type 1 exchanger (NHE-1) inhibition is an innovative pathway that has proved to efficiently prevent the accumulation of muscle damage (inflammation and fibrosis) in animal models of muscular dystrophies and heart failure. Based on prior safety and efficacy results in animal and humans, NHE-1 inhibition with Rimeporide represents a new therapeutic approach with no restriction on age and on genetic subtypes which could be combined to other treatments that restore or augment dystrophin.This study examines the safety and tolerability and effects on the muscles of rimeporide, in patients aged 6 to 14 years with Duchenne Muscular Dystrophy (DMD).
Detailed description
This study is designed as a phase Ib, multicenter, european, open label study to evaluate the safety and tolerability and biomarkers of a new drug, rimeporide, in boys aged 6 to 14 years with Duchenne Muscular Dystrophy (DMD).
Rimeporide will be taken orally for 4 weeks, three times a day. Dose will be adapted to body weight. The study will enrol 20 patients with DMD, aged 6 to 14 years. 4 dose levels will be tested, in 4 different cohorts with 5 patients taking the drug at each dose level.
During the study, there will be 6 visits in the Hospital over a maximum of 10 weeks. At each visit, patients will undergo safety examinations including vital signs, physical and neurological examinations, ECG, safety and hematology, biochemistry and urinalysis, concomitant treatments review, and any symptoms and side effects review. In addition, blood samples will be withdrawn for the evaluation of Rimeporide in plasma. Finally, additional blood \& urine samples will be collected to explore efficacy markers. Patients will also undergo 2 NMR (at screening and End of study) to develop non invasive biomarkers for further investigations in DMD patients.
The decision to progress to the next higher dose will be made after safety and tolerability data are reviewed for the preceding dose for 5 patients by SMC and determined that it is safe to proceed to the next dose level.
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rimeporide | Experimental | Drug: RimeporideMultiple oral doses of rimeporide ranging from 50 to 300 mg will be administered three times a day (TID) for a total of 4 weeks. 4 ascending dose levels will be studied sequentially in ascending order. Rimeporide is provided as hard gel 25 mg or 50 mg capsules. Each patient will participate in only 1 dose cohort. 5 patients are expected to be recruited in each cohort through all participating sites. |
Who may qualify
- Ages
- 6 to 14 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Duchenne muscular dystrophy genetically confirmed;
- Males between 6 and 14 years old;
- Able to walk independently at least 75 meters;
- Patients on a stable dose of corticosteroids at least 6 months prior to baseline;
- Patients able to swallow capsules size 4 according to the parents and investigator opinion;
Key exclusion criteria (17 listed)
- Patients with significant renal disease or impairment, with Glomerular Filtration Rate estimated using plasma cystatin C level using the Filler formula less than 90ml/min/1.73m2
- Current or history of liver disease or impairment,
- History of any significant medical disorder which may confound the interpretation of either efficacy or safety data e.g. inflammatory, coagulation disease, unstable cardiac or respiratory disease
- Acute illness within 4 weeks of the first administration of study medication which may interfere with study assessments;
- Significant change of dosage and/or dosing regimens for corticosteroids planned for the duration of study medication;
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 |
|---|---|---|
| RimeporideAlso: EMD 87580Cohort 1: 50 mg TID in patients with a body weight ≤ 30kg at Baseline and 75 mg TID in patients with a body weight > 30kg at Baseline Cohort 2: 100mg TID in patients with a body weight ≤ 30kg at baseline and 150 mg TID in patients with a body weight > 30kg at Baseline Cohort 3: 150 mg TID in patients with a body weight ≤ 30kg at baseline and 200 mg TID in patients with a body weight > 30kg at Baseline Cohort 4: 200 mg TID in patients with a body weight ≤ 30kg at Baseline and 300 mg TID mg TID in patients with a body weight > 30kg at Baseline | Drug | Rimeporide |
Primary outcome
Number of Participants With Adverse Events
Time frame: up to 6 weeks from first administration
Observations are given for the safety population (all patients who received at least one dose of study drug). Categorical data are presented with the number of subjects with at least one event for the following selections: * treatment-emergent AEs (TEAEs) * study drug-related TEAEs (ADRs) * serious TEAEs * study drug-related serious TEAEs (serious ADRs) * TEAEs leading to withdrawal * study drug-related TEAEs (ADRs) leading to withdrawal * serious TEAEs leading to withdrawal * TEAEs leading to death as outcome
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Sponsor websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Florence Porte-Thomé study director
R&D Director EspeRare
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Rimeporide in people with Muscular Dystrophy, Duchenne, run by EspeRare Foundation 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 18 Jul 2019. 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 France, Italy, Spain, United Kingdom. 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 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.
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 18 Jul 2019). 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 With Adverse Events (time frame: up to 6 weeks from first administration). 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 18 Jul 2019.