Safety and Efficacy of P-188 NF in DMD Patients

NCT03558958 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: P-004
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Duchenne Muscular Dystrophy

Outcome Measures

Primary Outcomes (1)

• Forced vital capacity (FVC)

  Change from baseline (pre-treatment) to end of treatment (52 weeks)

  Baseline, Days 91, 182, 273, 364

Secondary Outcomes (9)

• Maximal inspiratory pressure (MIP)

  Baseline, Days 91, 182, 273, 364

• Maximal expiratory pressure (MEP)

  Baseline, Days 91, 182, 273, 364

• Peak cough flow (PCF)

  Baseline, Days 91, 182, 273, 364

• Left ventricular end-diastolic volume (LVEDV)

  Baseline, Days 91, 182, 273, 364

• Ejection Fraction (EF)

  Baseline, Days 91, 182, 273, 364

Study Arms (1)

P-188 NF

EXPERIMENTAL

P-188 NF, 5 mg/Kg administered subcutaneously daily for 1 year

Drug: P-188 NF

Interventions

P-188 NF DRUG

Poloxamer administered daily via sc injection at 5 mg/Kg

Also known as: Carmeseal-MD

P-188 NF

Eligibility Criteria

• Age: 12 Years - 25 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Phrixus Pharmaceuticals, Inc.: lead
• Charley's Fund: collaborator

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (7)

• 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.

  PMID: 18495816 BACKGROUND

• Ilsar, 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

• 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.

  PMID: 20234088 BACKGROUND

• Houang 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.

  PMID: 26623440 BACKGROUND

• Lin 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.

  PMID: 25791035 BACKGROUND

• Plant 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

  BACKGROUND

• 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.

  BACKGROUND

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Thomas Ryan, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2018
• First Posted: June 15, 2018
• Study Start: August 8, 2018
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2021
• Last Updated: January 11, 2023

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)