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

NCT ID: NCT01415427

Last Updated: 2021-07-21

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

173 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-07-31

Study Completion Date

2016-06-16

Brief Summary

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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).

Detailed Description

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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

Conditions

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Mucopolysaccharidosis IV A Morquio A Syndrome MPS IVA

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

BMN 110 - Weekly

Intervention Type 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.

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.

Group Type EXPERIMENTAL

BMN 110 - Every Other Week

Intervention Type 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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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N-acetylgalactosamine-6-sulfatase N-acetylgalactosamine-6-sulfate sulfatase galactose-6-sulfatase GALNS enzyme replacement therapy ERT N-acetylgalactosamine-6-sulfatase N-acetylgalactosamine-6-sulfate sulfatase galactose-6-sulfatase GALNS enzyme replacement therapy ERT

Eligibility Criteria

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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.
Minimum Eligible Age

5 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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BioMarin Pharmaceutical

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Debra Lounsbury

Role: STUDY_DIRECTOR

BioMarin Pharmaceutical

Locations

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Phoenix, Arizona, United States

Site Status

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, , France

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Paris, , 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, , United Kingdom

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Birmingham, , United Kingdom

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Birmingham, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

Site Status

Countries

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United States Argentina Brazil Canada Colombia Denmark France Germany Italy Japan Netherlands Norway Portugal Qatar Saudi Arabia South Korea Spain Taiwan Turkey (Türkiye) United Kingdom

References

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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.

Reference Type DERIVED
PMID: 29248359 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28535791 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27955919 (View on PubMed)

Other Identifiers

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MOR-005

Identifier Type: -

Identifier Source: org_study_id

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