Long-Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)

NCT01415427 | Completed Phase 3 Results DMC

• 1 other identifier: MOR-005
• Study Type: interventional
• Target: 173
• Locations: 20 countries
• Sites: 43

Brief Summary

This Phase 3 extension study will evaluate the long-term efficacy and safety of BMN 110 2.0 mg/kg/week and/or BMN 110 2.0 mg/kg/every other week in patients with mucopolysaccharidosis IVA (Morquio A Syndrome).

Conditions

Mucopolysaccharidosis IV A; Morquio A Syndrome; MPS IVA

Keywords

Mucopolysaccharidosis IV type A; MPS IV Type A; Mucopolysaccharidosis IVA; MPS IVA; Morquio A Syndrome; Lysosomal Storage Disorder; LSD; N-acetylgalactosamine-6-sulfatase; N-acetylgalactosamine-6-sulfate sulfatase; galactose-6-sulfatase; GALNS; enzyme replacement therapy; ERT

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in 6-minute Walk (6MW) Test - ITT

  Efficacy was assessed by changes from baseline in 6-minute walk test

  Baseline to week 168

• Change From Baseline in 6-minute Walk (6MW) Test - MPP

  Efficacy was assessed by changes from baseline in 6-minute walk test

  Baseline to week 168

Secondary Outcomes (4)

• Change From Baseline in 3-minute Stair Climb Test - ITT

  Baseline to week 168

• Change From Baseline in 3-minute Stair Climb Test - MPP

  Baseline to week 168

• Change From Baseline in Urine Keratan Sulfate - ITT

  Baseline to week 168

• Change From Baseline in Urine Keratan Sulfate - MPP

  Baseline to week 168

Study Arms (2)

BMN 110 Weekly

EXPERIMENTAL

BMN 110 Weekly: In Part 1, patients will receive an intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours once a week.

Drug: BMN 110 - Weekly

BMN 110 Every Other Week

EXPERIMENTAL

BMN 110 Every Other Week: In Part 1, patients will receive an intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours every other week and will receive infusions of placebo on alternating weeks.

Drug: BMN 110 - Every Other Week

Interventions

BMN 110 - Weekly DRUG

In Part 1, patients will receive intravenous (IV) infusions of study drug at a dose of 2.0 mg/kg/qw administered over a period of approximately 4 hours once a week. In Part 2, patients will continue to receive 2.0 mg/kg of BMN 110 every week, with no placebo.

Also known as: N-acetylgalactosamine-6-sulfatase, N-acetylgalactosamine-6-sulfate sulfatase, galactose-6-sulfatase, GALNS, enzyme replacement therapy, ERT

BMN 110 Weekly

BMN 110 - Every Other Week DRUG

In Part 1, patients will receive intravenous (IV) infusions of study drug at a dose of 2.0 mg/kg administered over a period of approximately 4 hours every other week. Patients randomized to the 2.0 mg/kg/qow arm will receive infusions of placebo on alternating weeks, to mask active drug weeks. In Part 2, patients will receive 2.0 mg/kg of BMN 110 every week, with no placebo.

Also known as: N-acetylgalactosamine-6-sulfatase, N-acetylgalactosamine-6-sulfate sulfatase, galactose-6-sulfatase, GALNS, enzyme replacement therapy, ERT

BMN 110 Every Other Week

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have completed MOR-004
• Is willing and able to provide written, signed informed consent. Or in the case of patients under the age of 18 (or other age as defined by regional law or regulation), provide written assent (if required) and have written informed consent, signed by a legally authorize representative, after the nature of the study has been explained, and prior to performance of research-related procedures.
• If sexually active, must be willing to use an acceptable method of contraception while participating in the study.
• If female, of childbearing potential, must have a negative pregnancy test at Baseline and be willing to have additional pregnancy tests done during the study.

You may not qualify if:

• Is pregnant or breastfeeding, at Baseline, or planning to become pregnant (self or partner) at any time during the study.
• Has used any investigational product (other than BMN 110 in MOR-004), or investigational medical device, within 30 days prior to Baseline; or is required to use any investigational agent prior to completion of all scheduled study assessments.
• Was enrolled in a previous BMN 110 study, other than MOR-004.
• Has a concurrent disease or condition, including but not limited to, symptomatic cervical spine instability, clinically significant spinal cord compression, or severe cardiac disease that would interfere with study participation, or pose a safety risk, as determined by the Investigator.
• Has any condition that, in the view of the Investigator, places the patient at high risk of poor treatment compliance or of not completing the study.

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (43)

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Phoenix, Arizona, United States

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Oakland, California, United States

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Orange, California, United States

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Wilmington, Delaware, United States

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Washington D.C., District of Columbia, United States

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Orlando, Florida, United States

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Honolulu, Hawaii, United States

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Chicago, Illinois, United States

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New York, New York, United States

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Seattle, Washington, United States

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Córdoba, Argentina

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Campina Grande, Brazil

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Porto Alegre, Brazil

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Rio de Janeiro, Brazil

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Montreal, Canada

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Sherbrooke, Canada

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Toronto, Canada

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Bogotá, Colombia

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Copenhagen, Denmark

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Lyon, France

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Marseille, France

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Paris, Cedex 12, France

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Paris, Cedex 15, France

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Mainz, Germany

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Monza, Italy

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Tokyo, Japan

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Amsterdam, Netherlands

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Oslo, Norway

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Coimbra, Portugal

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Lisbon, Portugal

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Doha, Qatar

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Riyadh, Saudi Arabia

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Seoul, South Korea

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Santiago de Compostela, Spain

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Taipei, Taiwan

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Ankara, Turkey (Türkiye)

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Belfast, BT9 7AB, United Kingdom

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Birmingham, B15 2TH, United Kingdom

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Birmingham, B4 6NH, United Kingdom

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London, NW3 2PF, United Kingdom

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London, WC1N 3BG, United Kingdom

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London, WC1N 3JH, United Kingdom

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Manchester, M13 9WL, United Kingdom

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Related Publications (3)

• Hendriksz CJ, Parini R, AlSayed MD, Raiman J, Giugliani R, Mitchell JJ, Burton BK, Guelbert N, Stewart FJ, Hughes DA, Matousek R, Hawley SM, Decker C, Harmatz PR. Impact of long-term elosulfase alfa on activities of daily living in patients with Morquio A syndrome in an open-label, multi-center, phase 3 extension study. Mol Genet Metab. 2018 Feb;123(2):127-134. doi: 10.1016/j.ymgme.2017.11.015. Epub 2017 Dec 5.

  PMID: 29248359 DERIVED

• Hughes D, Giugliani R, Guffon N, Jones SA, Mengel KE, Parini R, Matousek R, Hawley SM, Quartel A. Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa. Orphanet J Rare Dis. 2017 May 23;12(1):98. doi: 10.1186/s13023-017-0634-0.

  PMID: 28535791 DERIVED

• Long B, Tompkins T, Decker C, Jesaitis L, Khan S, Slasor P, Harmatz P, O'Neill CA, Schweighardt B. Long-term Immunogenicity of Elosulfase Alfa in the Treatment of Morquio A Syndrome: Results From MOR-005, a Phase III Extension Study. Clin Ther. 2017 Jan;39(1):118-129.e3. doi: 10.1016/j.clinthera.2016.11.017. Epub 2016 Dec 10.

  PMID: 27955919 DERIVED

MeSH Terms

Conditions

Mucopolysaccharidosis IV; Lysosomal Storage Diseases

Interventions

Chondroitinases and Chondroitin Lyases; Galns protein, mouse; GALNS protein, human; Enzyme Replacement Therapy

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sulfatases; Esterases; Hydrolases; Enzymes; Enzymes and Coenzymes; Polysaccharide-Lyases; Carbon-Oxygen Lyases; Lyases; Enzyme Therapy; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Peter Slasor/Sr Director, Biostatistics, Global Clinical Sciences
• Organization: BioMarin Pharmaceutical Inc.

pslasor@bmrn.com

415-506-6765

Study Officials

• Debra Lounsbury

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2011
• First Posted: August 12, 2011
• Study Start: July 1, 2011
• Primary Completion: June 16, 2016
• Study Completion: June 16, 2016
• Last Updated: July 21, 2021
• Results First Posted: May 19, 2017

Record last verified: 2017-04

Locations

BR (3); AR (1); DK (1); PT (2); ES (1); QA (1); US (10); CA (3); TU (1); GB (7); CO (1); DE (1); FR (4); IT (1); TW (1); JP (1); NO (1); KR (1); SA (1); NL (1)