Prospective, Longitudinal Study of the Natural History and Functional Status of Patients With Myotubular Myopathy (MTM) (MTM)

• ClinicalTrials.gov Identifier: NCT02057705
• Recruitment Status: Completed
• First Posted: February 7, 2014
• Last Update Posted: June 7, 2018
• Sponsor: Valerion Therapeutics, LLC
• Collaborators: Institut de Myologie, France; Genethon
• Information provided by (Responsible Party): Valerion Therapeutics, LLC

Study Description

Brief Summary:

This is a prospective, non-interventional, longitudinal study of the natural history and function of approximately 60 patients with MTM from the United States, Canada and Europe. The duration of the study, including the enrollment period, will be 36 months. Data from the study will be used to characterize the disease course of MTM and determine which outcome measures will be the best to assess the efficacy of potential therapies.

Condition or disease
Myotubular Myopathy

Detailed Description:

This is a prospective, non-interventional, longitudinal study of the natural history and function of patients with MTM. The study duration is 36 months. The enrollment period will be 12 months and each patient will be assessed over 24 months. Data will be analyzed at baseline and annually thereafter and reports will be prepared based on these analyses. A final report will summarize findings after all patients have completed 24 months of follow-up. Assessments performed in this study will be based on the age and ambulatory status of the patient. The assessments will also be adjusted to account for the variability in both phenotypes and age of the patients who may participate in this study. Patients will be evaluated at Baseline, Month 6, Month 12 and Month 24. It is anticipated that approximately 60 patients from the United States, Canada and Europe will be included in this study.

Study Design

• Study Type: Observational
• Actual Enrollment: 48 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Prospective, Longitudinal Study of the Natural History and Functional Status of Patients With Myotubular Myopathy (MTM)
• Study Start Date: February 2014
• Actual Primary Completion Date: June 26, 2017
• Actual Study Completion Date: June 26, 2017

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Time to characterize the disease course in MTM patients [ Time Frame: Up to 24 Months ]
   Study-specific functional assessments and patient questionnaires will be used and will be based on the age and ambulatory status of the participant

Secondary Outcome Measures :

1. Change in disease severity and disease progression [ Time Frame: Baseline, Month 3 (EU only), Month 6, Month 12 and Month 24 ]
   Study-specific functional assessments and patient questionnaires will be used and will be based on the age and ambulatory status of the participant

Other Outcome Measures:

1. Number of participants with an immune response against adeno-associated virus (AAV) [ Time Frame: Baseline Visit ]
   A 5 ml sample of whole blood will be collected during the study to assess the immunity against various AAV serotypes.

Biospecimen Retention:   Samples With DNA

• 5 ml sample of whole blood will be collected during the study to assess the immunity against various AAV serotypes
• 5 ml blood sample may be obtained for peripheral blood mononuclear cells (PBMC) to quantify X-linked myotubular myopathy gene 1 (MTM1) production
• 24-hour urine collection will be performed every 6 months in order to measure urinary creatinine excretion
• Slides and tissue from a previously performed muscle biopsy will be obtained for a central review and quantification of histo- and immunohistopathological features of MTM

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Investigative Research Centers

Criteria

Inclusion criteria:

• Patients of any age (newborns included) may participate.
• Patients over 18 years of age and parent(s)/legal guardian(s) of patients <18 years of age must provide written informed consent prior to participating in the study and informed assent will be obtained from minors at least 7 years of age when required by regulation.
• MTM resulting from a mutation in the MTM1 gene.
• Male or symptomatic female. A symptomatic female will be defined by the motor function assessment by Motor Function Measure (MFM) or North Star Ambulatory Assessment (NSAA) below 80% of the total score.
• Willing and able to comply with all protocol requirements and procedures.

Exclusion criteria:

• Other disease which may significantly interfere with the assessment of MTM and is clearly not related to the disease.
• Currently enrolled in a treatment study; or treatment with an experimental therapy other than pyridostigmine.

Contacts and Locations

Locations

United States, Massachusetts

Boston Children's Hospital, 300 Longwood Avenue

Boston, Massachusetts, United States, 02115

Belgium

Centre Hospitalier Regional de la Citadelle

Liège, Belgium, 4000

Canada, Ontario

Hospital for Sick Children, 555 University Avenue

Toronto, Ontario, Canada, M5G 1X8

France

Hôpital Femme Mère Enfant, CHU Lyon Escale

Bron, France, 69500

Roger Salengro Hospital, CHU, Lille

Lille, France, 59000

Croix Rousse Hospital

Lyon, France, 69004

Institut de Myologie, GH Pitié Salpêtrière, Bâtiment Babinski

Paris Cedex 13, France, 75651

Hôpital Armand Trousseau

Paris, France, 75012

Institut I-Motion, Hôpital A. Trousseau

Paris, France, 75012

Hôpital Sainte Musse

Toulon, France, 83056

Germany

University Hospital of Essen

Essen, Germany, D-45147

Italy

Bambino Gesù Children's Hospital

Rome, Italy, 4-00165

Spain

Hôpital Puertas de Mar

Cadiz, Spain, 21-11009

Sponsors and Collaborators

Valerion Therapeutics, LLC

Institut de Myologie, France

Genethon

Investigators

• Study Director: Hal Landy, MD; Valerion Therapeutics, LLC

More Information

Additional Information:

National Institute of Health 

Muscular Dystrophy Association 

Publications:

Herman GE, Finegold M, Zhao W, de Gouyon B, Metzenberg A. Medical complications in long-term survivors with X-linked myotubular myopathy. J Pediatr. 1999 Feb;134(2):206-14. doi: 10.1016/s0022-3476(99)70417-8.

Jungbluth H, Sewry CA, Buj-Bello A, Kristiansen M, Orstavik KH, Kelsey A, Manzur AY, Mercuri E, Wallgren-Pettersson C, Muntoni F. Early and severe presentation of X-linked myotubular myopathy in a girl with skewed X-inactivation. Neuromuscul Disord. 2003 Jan;13(1):55-9. doi: 10.1016/s0960-8966(02)00194-3.

McEntagart M, Parsons G, Buj-Bello A, Biancalana V, Fenton I, Little M, Krawczak M, Thomas N, Herman G, Clarke A, Wallgren-Pettersson C. Genotype-phenotype correlations in X-linked myotubular myopathy. Neuromuscul Disord. 2002 Dec;12(10):939-46. doi: 10.1016/s0960-8966(02)00153-0.

Jungbluth H, Wallgren-Pettersson C, Laporte J. Centronuclear (myotubular) myopathy. Orphanet J Rare Dis. 2008 Sep 25;3:26. doi: 10.1186/1750-1172-3-26.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Annoussamy M, Lilien C, Gidaro T, Gargaun E, Che V, Schara U, Gangfuss A, D'Amico A, Dowling JJ, Darras BT, Daron A, Hernandez A, de Lattre C, Arnal JM, Mayer M, Cuisset JM, Vuillerot C, Fontaine S, Bellance R, Biancalana V, Buj-Bello A, Hogrel JY, Landy H, Servais L. X-linked myotubular myopathy: A prospective international natural history study. Neurology. 2019 Apr 16;92(16):e1852-e1867. doi: 10.1212/WNL.0000000000007319. Epub 2019 Mar 22.

• Responsible Party: Valerion Therapeutics, LLC
• ClinicalTrials.gov Identifier: NCT02057705
• Other Study ID Numbers: VAL-101-13
• First Posted: February 7, 2014
• Last Update Posted: June 7, 2018
• Last Verified: June 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Valerion Therapeutics, LLC:

MTM; myotubular myopathy; X-linked centronuclear myopathy; inherited myopathies; neuromuscular diseases; hypotonia; genetic mutation

Additional relevant MeSH terms:

Muscular Diseases; Myopathies, Structural, Congenital; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases