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

A Multicenter, Multinational, Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)

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).

Study Overview

• Status: Completed
• Conditions: Morquio A Syndrome; MPS IVA; Mucopolysaccharidosis IV A
• Intervention / Treatment: Drug: BMN 110 - Weekly; Drug: BMN 110 - Every Other Week

Detailed Description

This is a multi-center, multinational, extension study to evaluate 2 dose regimens of BMN 110 treatment in patients with MPS IVA who completed MOR-004.

The last study visit assessments for MOR-004 will constitute Baseline for this study. The first study drug dose of this protocol will occur on Week 0 of MOR-005, which is the same as the last visit (Week 24) of MOR-004. Initially, the study will be double-blind with patients previously randomized to BMN 110 in MOR-004 remaining on their assigned BMN 110 dose regimen (qw or qow dosing). The MOR-004 placebo patients will be re-randomized (1:1 ratio) to one of the 2 BMN 110 dose regimen groups: 2.0 mg/kg/qw or 2.0 mg/kg/qow.

There will be two study parts:

• Part 1 - randomized double-blind until the optimal BMN 110 dose regimen has been determined, based on the final primary efficacy analysis from MOR-004
• Part 2 - open-label BMN 110 treatment with the single optimal dose regimen

• Study Type: Interventional
• Enrollment (Actual): 173
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina
• Brazil
  • Campina Grande, Brazil
  • Porto Alegre, Brazil
  • Rio de Janeiro, Brazil
• Canada
  • Montreal, Canada
  • Sherbrooke, Canada
  • Toronto, Canada
• Colombia
  • Bogota, Colombia
• Denmark
  • Copenhagen, Denmark
• France
  • Lyon, France
  • Marseille, France
  • Paris, France, Cedex 12
  • Paris, France, Cedex 15
• Germany
  • Mainz, Germany
• Italy
  • Monza, Italy
• Japan
  • Tokyo, Japan
• Korea, Republic of
  • Seoul, Korea, Republic of
• Netherlands
  • Amsterdam, Netherlands
• Norway
  • Oslo, Norway
• Portugal
  • Coimbra, Portugal
  • Lisbon, Portugal
• Qatar
  • Doha, Qatar
• Saudi Arabia
  • Riyadh, Saudi Arabia
• Spain
  • Santiago de Compostela, Spain
• Taiwan
  • Taipei, Taiwan
• Turkey
  • Ankara, Turkey
• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
  • Birmingham, United Kingdom, B15 2TH
  • Birmingham, United Kingdom, B4 6NH
  • London, United Kingdom, WC1N 3BG
  • London, United Kingdom, WC1N 3JH
  • London, United Kingdom, NW3 2PF
  • Manchester, United Kingdom, M13 9WL
• United States
  • Arizona
    • Phoenix, Arizona, United States
  • California
    • Oakland, California, United States
    • Orange, California, United States
  • Delaware
    • Wilmington, Delaware, United States
  • District of Columbia
    • Washington, District of Columbia, United States
  • Florida
    • Orlando, Florida, United States
  • Hawaii
    • Honolulu, Hawaii, United States
  • Illinois
    • Chicago, Illinois, United States
  • New York
    • New York, New York, United States
  • Washington
    • Seattle, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BMN 110 Weekly; 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; 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.; Other Names: ERT; N-acetylgalactosamine-6-sulfatase; N-acetylgalactosamine-6-sulfate sulfatase; galactose-6-sulfatase; GALNS; enzyme replacement therapy
Experimental: BMN 110 Every Other Week; 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; 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.; Other Names: ERT; N-acetylgalactosamine-6-sulfatase; N-acetylgalactosamine-6-sulfate sulfatase; galactose-6-sulfatase; GALNS; enzyme replacement therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 3-minute Stair Climb Test - ITT	Efficacy was assessed by changes from baseline in 3-minute stair climb test.	Baseline to week 168
Change From Baseline in 3-minute Stair Climb Test - MPP	Efficacy was assessed by changes from baseline in 3-minute stair climb test.	Baseline to week 168
Change From Baseline in Urine Keratan Sulfate - ITT	Efficacy was assessed by changes from baseline in urine keratan sulfate (normalized to urine creatinine.)	Baseline to week 168
Change From Baseline in Urine Keratan Sulfate - MPP	Efficacy was assessed by changes from baseline in urine keratan sulfate (normalized to urine creatinine.)	Baseline to week 168

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): June 16, 2016
• Study Completion (Actual): June 16, 2016

Study Registration Dates

• First Submitted: August 8, 2011
• First Submitted That Met QC Criteria: August 11, 2011
• First Posted (Estimate): August 12, 2011

Study Record Updates

• Last Update Posted (Actual): July 21, 2021
• Last Update Submitted That Met QC Criteria: July 19, 2021
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: enzyme replacement therapy; Lysosomal Storage Disorder; GALNS; Mucopolysaccharidosis IV type A; MPS IV Type A; Mucopolysaccharidosis IVA; MPS IVA; Morquio A Syndrome; LSD; N-acetylgalactosamine-6-sulfatase; N-acetylgalactosamine-6-sulfate sulfatase; galactose-6-sulfatase; ERT
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Disease; Genetic Diseases, Inborn; Musculoskeletal Diseases; Connective Tissue Diseases; Bone Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Bone Diseases, Developmental; Syndrome; Mucopolysaccharidoses; Osteochondrodysplasias; Mucopolysaccharidosis IV
• Other Study ID Numbers: MOR-005