Duchenne Muscular DystrophyPhase 2NCT03558958
Safety and Efficacy of P-188 NF in DMD Patients
A Phase 2 study testing P-188 NF in people with Duchenne Muscular Dystrophy, run by Phrixus Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
This is an open-label study to evaluate the safety, tolerability and efficacy of daily, subcutaneous dosing with P-188 NF (Carmeseal-MD™) in non-ambulatory boys with Duchenne Muscular Dystrophy (DMD). Read more about this study
- Who is it for?
- Ages 12 to 25 years, men only
- Conditions the study is for
- Duchenne Muscular Dystrophy
- What is being tested?
- P-188 NF
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Aug 2018to 1 Sep 2021
- 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 12 to 25 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Male
- 12 - 25 years of age
- Have phenotypic evidence of DMD
- Have documentation of the presence of a deletion, duplication or point mutation in the dystrophin gene
- Willingness to receive daily subcutaneous (SC) injections of up to 3 mL
- Have LVEDV that is ≥100% of normal corrected for body mass when measured by cardiac MRI
Show all 17Show fewer
- Have impaired respiratory function (percent predicted PEF ≤80%)
- Have ability to perform PEF within 15% of first assessment
- Have mild to moderate fibrosis of the heart as assessed by MRI
- Have left ventricular ejection fraction fractions of <50%
- Have been non-ambulatory for at least six months
- Be on corticosteroids, with a stable treatment regimen for at least six months
- Have been on a stable treatment regimen for cardiac dysfunction for at least 3 months prior to baseline (ACE inhibitors, beta blockers and/or ARBs)
- Have clinically acceptable screening values, including serum creatinine levels blood urine nitrogen, cystatin C
- Have willingness and ability to comply with scheduled visits, drug administration, drug administrative plan, study procedures, laboratory tests, and treatment restrictions
- Be likely to survive for the duration of the treatment in the investigator's opinion
- Have ability to provide written informed consent (parent/guardian consent if applicable)/assent (if <18 years of age).
Who cannot join
- Exposure to another investigational drug within 90 days prior to start of study treatment
- Have DMD-related hypoventilation for which daytime assisted ventilation is needed
- Unable to perform pulmonary function testing
- Have respiratory failure
- Unable or unwilling to undergo scan with gadolinium as contrast agent
- Unable or unwilling to undergo echocardiography
Show all 18Show fewer
- Have severe fibrosis of the heart as assessed by MRI
- Used carnitine, creatine, glutamine, oxatomide, coenzyme Q10 or vitamin E or any herbal medicines with 30 days prior to baseline
- Have a history of major surgical procedure within 30 days prior to start of study treatment
- Have ongoing immunosuppressive therapy (other than corticosteroids)
- Are participating in a therapeutic clinical trial
- Are on any concomitant medication with a depressive or stimulating effect on respiration or the respiratory tract
- Have a diagnosis of chronic lung disease
- Chronic use of beta-2 agonists or any other bronchodilating medication (chronic use is daily intake for more than 14 days within the last 6 months)
- Have moderate or severe hepatic impairment or moderate to severe renal impairment
- Have expectation of major surgical procedure during the conduct of the study
- Have prior or ongoing medical conditions that makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of the treatment results
- Have ever previously received P-188 NF as a therapeutic agent
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: An Exploratory, Open-label Study to Assess the Effect of P-188 NF (Carmeseal-MD) on Safety, on Respiratory and Cardiac Dysfunction and on Upper Limb Strength in Non-ambulatory Patients With Duchenne Muscular Dystrophy (DMD)
This is an open-label study to evaluate the safety, tolerability and efficacy of daily, subcutaneous dosing with P-188 NF (Carmeseal-MD™) in non-ambulatory boys with Duchenne Muscular Dystrophy (DMD). This study will determine if continuous treatment with Carmeseal-MD™ can maintain or improve pulmonary function, and skeletal and cardiac muscle function, compared to baseline, in boys 12-25 years of age.
Read the detailed description
Based on a large number of studies conducted in pre-clinical models of muscular dystrophy and heart failure, this study is being undertaken to explore the safety and efficacy of Carmeseal-MD™ (P-188 NF) on endpoints associated with cardiovascular, pulmonary and musculoskeletal function. These preclinical studies indicate that Carmeseal-MD™ acts to stabilize fragile cell membranes thus maintaining cell function and preventing fibrosis, necrosis and apoptosis in animal models of muscular dystrophy.
This is a single arm, open label trial that is designed to provide a first evaluation of Carmeseal-MD™ in non-ambulatory patients with DMD. It assigns up to ten (10) patients to receive a fixed dose of 5 mg of P-188 NF per Kg patient body weight (adjusted individually for each patient at baseline visit) injected subcutaneously once-a-day for 52 weeks. The first 3 enrolled subjects (Group 1) will be at least 18 years of age and up to 25 years of age. Enrollment of Group 2 will begin after a review of Group 1 safety data through 28 days of dosing of Carmeseal-MD™. Group 2 will include subjects that are at least 12 years of age and up to 25 years old. Evaluations will be for Carmeseal-MD™ administered in addition to the current standard of care therapies and interventions such as corticosteroids, ACE inhibitors, ARBs, beta blockers, bronchodilator medications and airway clearance, cough assist and non-invasive ventilation devices.
The major hypothesis for the trial is that measures of function of skeletal and cardiac muscle that decline over the course of the disease will either remain stable or improve with P-188 NF treatment when a decline would be expected. To assess these possible beneficial effects, comparisons are planned between pre- and post-treatment on measures of function for the various body systems affected by DMD.
- Conditions
- Duchenne Muscular Dystrophy
- Being tested
- P-188 NF
- 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.
P-188 NFDrug
Also called Carmeseal-MD
Poloxamer administered daily via sc injection at 5 mg/Kg
| Study group | Role | What they receive |
|---|---|---|
| P-188 NF | Experimental | P-188 NF, 5 mg/Kg administered subcutaneously daily for 1 year Receives: Drug: P-188 NF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Forced vital capacity (FVC)
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Measured: Baseline, Days 91, 182, 273, 364
Secondary outcomes (9)
Maximal inspiratory pressure (MIP)
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Measured: Baseline, Days 91, 182, 273, 364
Maximal expiratory pressure (MEP)
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Measured: Baseline, Days 91, 182, 273, 364
Peak cough flow (PCF)
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Measured: Baseline, Days 91, 182, 273, 364
Left ventricular end-diastolic volume (LVEDV)
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Measured: Baseline, Days 91, 182, 273, 364
Ejection Fraction (EF)
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Measured: Baseline, Days 91, 182, 273, 364
Degree of fibrosis as assessed by cardiac MRI
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Measured: Baseline, Days 182, 364
Performance of upper limb (PUL) test
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Measured: Baseline, Days 91, 182, 273, 364
Cardiac troponin I
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Measured: Baseline, Days 28, 56, 91, 182, 273, 364
Muscle creatine kinase
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Measured: Baseline, Days 28, 56, 91, 182, 273, 364
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2018
- Study start8 Aug 2018
- Primary completion1 Sep 2021
- Study completion1 Sep 2021
Why it stopped: Terminated due to lack of funding.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Duchenne Muscular DystrophyStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Phrixus Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Charley's Fund
- Responsible party
- Sponsor
- Investigators
- Thomas Ryan, MD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03558958
- Sponsor's protocol ID
- P-004
- Status last verified
- Sep 2021
- First submitted
- 5 Jun 2018
- Last updated
- 11 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ng R, Metzger JM, Claflin DR, Faulkner JA. Poloxamer 188 reduces the contraction-induced force decline in lumbrical muscles from mdx mice. Am J Physiol Cell Physiol. 2008 Jul;295(1):C146-50. doi: 10.1152/ajpcell.00017.2008. Epub 2008 May 21.
PubMed 18495816Ilsar, I., Wang, M., Jiang, A., Dye, K., Markham, B., Sabbah, H.N. (2010) Acute intravenous bolus injection of Poloxamer-188 improves left ventricular function in dogs with heart failure J. Am. Col. Cardiol. 55 (Suppl. 1): A16.E146.
Townsend D, Turner I, Yasuda S, Martindale J, Davis J, Shillingford M, Kornegay JN, Metzger JM. Chronic administration of membrane sealant prevents severe cardiac injury and ventricular dilatation in dystrophic dogs. J Clin Invest. 2010 Apr;120(4):1140-50. doi: 10.1172/JCI41329. Epub 2010 Mar 15.
PubMed 20234088Houang EM, Haman KJ, Filareto A, Perlingeiro RC, Bates FS, Lowe DA, Metzger JM. Membrane-stabilizing copolymers confer marked protection to dystrophic skeletal muscle in vivo. Mol Ther Methods Clin Dev. 2015 Nov 11;2:15042. doi: 10.1038/mtm.2015.42. eCollection 2015.
PubMed 26623440Lin B, Li Y, Han L, Kaplan AD, Ao Y, Kalra S, Bett GC, Rasmusson RL, Denning C, Yang L. Modeling and study of the mechanism of dilated cardiomyopathy using induced pluripotent stem cells derived from individuals with Duchenne muscular dystrophy. Dis Model Mech. 2015 May;8(5):457-66. doi: 10.1242/dmm.019505. Epub 2015 Mar 19.
PubMed 25791035Plant DR, Ryall JG, Lynch GS. Contraction-mediated damage in mdx dystrophic mouse tibialis anterior muscles is not affected by the membrane sealant poloxamer Proc. Australia Physiological Society. 2005; 36: 133P
Ryall JG, van der Poel C, Schertzer JD, Plant DR, Lynch GS, The membrane sealant poloxamer reduces membrane permeability in tibialis anterior muscles from dystrophic mdx mice. The FASEB Journal. 2007;21: 769.28.
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory, Open-label Study to Assess the Effect of P-188 NF (Carmeseal-MD) on Safety, on Respiratory and Cardiac Dysfunction and on Upper Limb Strength in Non-ambulatory Patients With Duchenne Muscular Dystrophy (DMD)
- ClinicalTrials.gov ID
- NCT03558958
- Acronym / sponsor ID
- P-004
- Conditions
- Duchenne Muscular Dystrophy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated due to lack of funding.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Phrixus Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Charley's Fund
- Study start
- 8 Aug 2018 (actual)
- Primary completion
- 1 Sep 2021 (actual)
- Study completion
- 1 Sep 2021 (actual)
- First posted
- 15 Jun 2018 (actual)
- 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.
This is an open-label study to evaluate the safety, tolerability and efficacy of daily, subcutaneous dosing with P-188 NF (Carmeseal-MD™) in non-ambulatory boys with Duchenne Muscular Dystrophy (DMD). This study will determine if continuous treatment with Carmeseal-MD™ can maintain or improve pulmonary function, and skeletal and cardiac muscle function, compared to baseline, in boys 12-25 years of age.
Detailed description
Based on a large number of studies conducted in pre-clinical models of muscular dystrophy and heart failure, this study is being undertaken to explore the safety and efficacy of Carmeseal-MD™ (P-188 NF) on endpoints associated with cardiovascular, pulmonary and musculoskeletal function. These preclinical studies indicate that Carmeseal-MD™ acts to stabilize fragile cell membranes thus maintaining cell function and preventing fibrosis, necrosis and apoptosis in animal models of muscular dystrophy.
This is a single arm, open label trial that is designed to provide a first evaluation of Carmeseal-MD™ in non-ambulatory patients with DMD. It assigns up to ten (10) patients to receive a fixed dose of 5 mg of P-188 NF per Kg patient body weight (adjusted individually for each patient at baseline visit) injected subcutaneously once-a-day for 52 weeks. The first 3 enrolled subjects (Group 1) will be at least 18 years of age and up to 25 years of age. Enrollment of Group 2 will begin after a review of Group 1 safety data through 28 days of dosing of Carmeseal-MD™. Group 2 will include subjects that are at least 12 years of age and up to 25 years old. Evaluations will be for Carmeseal-MD™ administered in addition to the current standard of care therapies and interventions such as corticosteroids, ACE inhibitors, ARBs, beta blockers, bronchodilator medications and airway clearance, cough assist and non-invasive ventilation devices.
The major hypothesis for the trial is that measures of function of skeletal and cardiac muscle that decline over the course of the disease will either remain stable or improve with P-188 NF treatment when a decline would be expected. To assess these possible beneficial effects, comparisons are planned between pre- and post-treatment on measures of function for the various body systems affected by DMD.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| P-188 NF | Experimental | Drug: P-188 NFP-188 NF, 5 mg/Kg administered subcutaneously daily for 1 year |
Who may qualify
- Ages
- 12 to 25 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (17 listed)
- Male
- 12 - 25 years of age
- Have phenotypic evidence of DMD
- Have documentation of the presence of a deletion, duplication or point mutation in the dystrophin gene
- Willingness to receive daily subcutaneous (SC) injections of up to 3 mL
Key exclusion criteria (18 listed)
- Exposure to another investigational drug within 90 days prior to start of study treatment
- Have DMD-related hypoventilation for which daytime assisted ventilation is needed
- Unable to perform pulmonary function testing
- Have respiratory failure
- Unable or unwilling to undergo scan with gadolinium as contrast agent
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 |
|---|---|---|
| P-188 NFAlso: Carmeseal-MDPoloxamer administered daily via sc injection at 5 mg/Kg | Drug | P-188 NF |
Primary outcome
Forced vital capacity (FVC)
Time frame: Baseline, Days 91, 182, 273, 364
Change from baseline (pre-treatment) to end of treatment (52 weeks)
9 secondary outcomes
Maximal inspiratory pressure (MIP)
Time frame: Baseline, Days 91, 182, 273, 364
Maximal expiratory pressure (MEP)
Time frame: Baseline, Days 91, 182, 273, 364
Peak cough flow (PCF)
Time frame: Baseline, Days 91, 182, 273, 364
Left ventricular end-diastolic volume (LVEDV)
Time frame: Baseline, Days 91, 182, 273, 364
Ejection Fraction (EF)
Time frame: Baseline, Days 91, 182, 273, 364
Degree of fibrosis as assessed by cardiac MRI
Time frame: Baseline, Days 182, 364
Performance of upper limb (PUL) test
Time frame: Baseline, Days 91, 182, 273, 364
Cardiac troponin I
Time frame: Baseline, Days 28, 56, 91, 182, 273, 364
Muscle creatine kinase
Time frame: Baseline, Days 28, 56, 91, 182, 273, 364
Results and safety
The study was stopped early (reason given: Terminated due to lack of funding.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2023.
- Background: PubMed 18495816Ng R, Metzger JM, Claflin DR, Faulkner JA. Poloxamer 188 reduces the contraction-induced force decline in lumbrical muscles from mdx mice. Am J Physiol Cell Physiol. 2008 Jul;295(1):C146-50. doi: 10.1152/ajpcell.00017.2008. Epub 2008 May 21.
- BackgroundIlsar, I., Wang, M., Jiang, A., Dye, K., Markham, B., Sabbah, H.N. (2010) Acute intravenous bolus injection of Poloxamer-188 improves left ventricular function in dogs with heart failure J. Am. Col. Cardiol. 55 (Suppl. 1): A16.E146.
- Background: PubMed 20234088Townsend D, Turner I, Yasuda S, Martindale J, Davis J, Shillingford M, Kornegay JN, Metzger JM. Chronic administration of membrane sealant prevents severe cardiac injury and ventricular dilatation in dystrophic dogs. J Clin Invest. 2010 Apr;120(4):1140-50. doi: 10.1172/JCI41329. Epub 2010 Mar 15.
- Background: PubMed 26623440Houang EM, Haman KJ, Filareto A, Perlingeiro RC, Bates FS, Lowe DA, Metzger JM. Membrane-stabilizing copolymers confer marked protection to dystrophic skeletal muscle in vivo. Mol Ther Methods Clin Dev. 2015 Nov 11;2:15042. doi: 10.1038/mtm.2015.42. eCollection 2015.
- Background: PubMed 25791035Lin B, Li Y, Han L, Kaplan AD, Ao Y, Kalra S, Bett GC, Rasmusson RL, Denning C, Yang L. Modeling and study of the mechanism of dilated cardiomyopathy using induced pluripotent stem cells derived from individuals with Duchenne muscular dystrophy. Dis Model Mech. 2015 May;8(5):457-66. doi: 10.1242/dmm.019505. Epub 2015 Mar 19.
- BackgroundPlant DR, Ryall JG, Lynch GS. Contraction-mediated damage in mdx dystrophic mouse tibialis anterior muscles is not affected by the membrane sealant poloxamer Proc. Australia Physiological Society. 2005; 36: 133P
- BackgroundRyall JG, van der Poel C, Schertzer JD, Plant DR, Lynch GS, The membrane sealant poloxamer reduces membrane permeability in tibialis anterior muscles from dystrophic mdx mice. The FASEB Journal. 2007;21: 769.28.
- 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.
Thomas Ryan, MD principal investigator
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing P-188 NF in people with Duchenne Muscular Dystrophy, run by Phrixus Pharmaceuticals, Inc. at 1 site in United States.
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 17 inclusion and 18 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 11 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 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: Terminated due to lack of funding.). 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?
Forced vital capacity (FVC) (time frame: Baseline, Days 91, 182, 273, 364). 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 NCT03558958, which also lists 7 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 11 Jan 2023.