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Natural History of Atypical Morquio A Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03204370
Recruitment Status : Recruiting
First Posted : July 2, 2017
Last Update Posted : February 6, 2019
BioMarin Pharmaceutical
Information provided by (Responsible Party):
GOIZET, Association Aquitaine de Recherche Clinique en Rhumatologie

Brief Summary:

Mucopolysaccharidosis IVA (MPS IVA) (or Morquio A disease) is a rare recessive autosomal lysosomal storage disorder caused by deficiency of N-acetylgalactosamine-6-sulfatase (GALNS) resulting in accumulation of the glycosaminoglycans (GAGs) chondroitin-6-sulfate and keratin sulfate (KS). Patients display progressive development of skeletal and joint abnormalities and non-skeletal features including respiratory, cardiac, sensorial and neurological complications. Recently, a specific treatment using enzyme replacement therapy (ERT) with recombinant human GALNS (elosulfase alfa) has become available. A multicenter double-blind placebo-controlled phase 3 trial (176 patients, age > 5 yrs) showed significant improvement in endurance of 22.5 m in 6 Minute Walking Test (6MWT) distance after 24 weeks of treatment with elosulfase alfa at 2.0 mg/kg/week as compared with placebo group. In addition to ERT, a multidisciplinary management approach is necessary for coordinating assessment and follow-up as well as for providing individualized supportive and symptomatic care.

The clinical presentation is highly variable from one patient to another regarding age at onset, severity, progression rate and life expectancy. Most patients are affected with the classical phenotype characterized by short trunk dwarfism with short neck and adult height < 1 m. Atypical phenotypes with less severe extension of skeletal manifestations, adult height > 1m, and less frequent complications in other organs have been progressively recognized. Clinical management differs depending on the clinical presentation of the patients but natural history of the disease is largely unknown in atypical phenotypes. Precise and exhaustive follow-up data are needed in such patients to increase our knowledge of this natural history and to define the best criteria to evaluate ERT efficiency.

The investigators propose a prospective clinical study focused on a unique large series of 9 adult patients (aged from 18 to 55 years) followed in a single expert center for metabolic disorders located at the university hospital of Bordeaux, France. Eight of these patients are affected with atypical MPS IVA characterized by less severe evolution of the disease and heights ranging from 135 to 176 cm (the last patient height is 102 cm). Investigators aim to increase knowledge on the natural history of the disease in adult patients with atypical MPS IVA, treated or not with ERT, and to develop new objective and robust clinical criteria to evaluate the efficiency of ERT over time, particularly in patients presenting an atypical phenotype. The entire cohort treated or not treated with ERT, will be evaluated at baseline and every year during a 5-years period. The complete evaluation at baseline will be our absolute priority as well as obtaining long-term and exhaustive follow up of the patients treated with ERT (two patients of the cohort already treated, and ERT expected in three additional patients in the next months).

The investigators designed a schedule of systematic and exhaustive assessments based on the recommended follow up from experts panel consensus meeting (MorCAP protocol) extended to some additional investigations including motor, cardiac and rheumatologic exams as our specific focus.

Condition or disease Intervention/treatment
Mucopolysaccharidosis IV A Drug: Elosulfase Alfa 1 MG/ML Intravenous Solution [VIMIZIM]

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Study Type : Observational
Estimated Enrollment : 9 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Natural History of Atypical Morquio A Disease: a 5-years Prospective Study in a Series of 9 Adult Patients Followed in a Single Expert Center
Actual Study Start Date : February 1, 2018
Estimated Primary Completion Date : February 1, 2020
Estimated Study Completion Date : July 1, 2023

Group/Cohort Intervention/treatment
MPS4A patients Drug: Elosulfase Alfa 1 MG/ML Intravenous Solution [VIMIZIM]
A subgroup of MPS4A patients will be treated by VIMIZIM drug, prescribed in usual care

Primary Outcome Measures :
  1. 6-minute-walking test [ Time Frame: through study completion, an average of 5 years ]
    distance made by the patient during a 6-minute-walking test

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
An unique large series of 9 adult patients (aged from 18 to 55 years) followed in a single expert center for metabolic disorders.

Inclusion Criteria:

  • MPS4A affected patients
  • Height more than 1 m (atypical phenotypes)
  • Treatment by ERT or not
  • Followed in our expert center
  • Having signed an inform consent form
  • Being affiliated to a health insurance system

Exclusion Criteria:

  • Patients affected by another disease
  • Patients refusing to participate to the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03204370

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Rheumatology department - Bordeaux University Hospital Recruiting
Bordeaux, Aquitaine, France, 33076
Contact: Christophe Richez, MD, PhD    0033(0)556795556   
Contact: Thomas Barnetche, PhD    0033557820493   
Sponsors and Collaborators
BioMarin Pharmaceutical

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Responsible Party: GOIZET, Professor, Association Aquitaine de Recherche Clinique en Rhumatologie Identifier: NCT03204370    
Other Study ID Numbers: BMRN58492
First Posted: July 2, 2017    Key Record Dates
Last Update Posted: February 6, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Mucopolysaccharidosis IV
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Connective Tissue Diseases
Metabolic Diseases
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases