Safety and Efficacy of P-188 NF in DMD Patients

January 9, 2023 updated by: Phrixus Pharmaceuticals, Inc.

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

2

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 25 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • 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
  • 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).

Exclusion Criteria:

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: P-188 NF
P-188 NF, 5 mg/Kg administered subcutaneously daily for 1 year
Drug: P-188 NF
Poloxamer administered daily via sc injection at 5 mg/Kg
Other Names:
  • Carmeseal-MD

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Forced vital capacity (FVC)
Time Frame: Baseline, Days 91, 182, 273, 364
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Baseline, Days 91, 182, 273, 364

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximal inspiratory pressure (MIP)
Time Frame: Baseline, Days 91, 182, 273, 364
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Baseline, Days 91, 182, 273, 364
Maximal expiratory pressure (MEP)
Time Frame: Baseline, Days 91, 182, 273, 364
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Baseline, Days 91, 182, 273, 364
Peak cough flow (PCF)
Time Frame: Baseline, Days 91, 182, 273, 364
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Baseline, Days 91, 182, 273, 364
Left ventricular end-diastolic volume (LVEDV)
Time Frame: Baseline, Days 91, 182, 273, 364
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Baseline, Days 91, 182, 273, 364
Ejection Fraction (EF)
Time Frame: Baseline, Days 91, 182, 273, 364
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Baseline, Days 91, 182, 273, 364
Degree of fibrosis as assessed by cardiac MRI
Time Frame: Baseline, Days 182, 364
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Baseline, Days 182, 364
Performance of upper limb (PUL) test
Time Frame: Baseline, Days 91, 182, 273, 364
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Baseline, Days 91, 182, 273, 364
Cardiac troponin I
Time Frame: Baseline, Days 28, 56, 91, 182, 273, 364
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Baseline, Days 28, 56, 91, 182, 273, 364
Muscle creatine kinase
Time Frame: Baseline, Days 28, 56, 91, 182, 273, 364
Change from baseline (pre-treatment) to end of treatment (52 weeks)
Baseline, Days 28, 56, 91, 182, 273, 364

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Phrixus Pharmaceuticals, Inc.

Collaborators

Charley's Fund

Investigators

  • Principal Investigator: Thomas Ryan, MD, Children's Hospital Medical Center, Cincinnati

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 8, 2018

Primary Completion (Actual)

September 1, 2021

Study Completion (Actual)

September 1, 2021

Study Registration Dates

First Submitted

June 5, 2018

First Submitted That Met QC Criteria

June 5, 2018

First Posted (Actual)

June 15, 2018

Study Record Updates

Last Update Posted (Estimate)

January 11, 2023

Last Update Submitted That Met QC Criteria

January 9, 2023

Last Verified

September 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P-004

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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