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A Study to Evaluate the Safety, Tolerability and Efficacy of BMN 110 in Subjects With Mucopolysaccharidosis IVA

Primary Purpose

MPS IV A

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

BMN 110

About this trial

This is an interventional treatment trial for MPS IV A focused on measuring 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

Eligibility Criteria

5 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Documented history of reduced GALNS activity relative to the normal range of the laboratory performing the assay, or documented result of molecular genetic testing confirming diagnosis of MPS IVA.
Willing and able to provide written, signed informed consent, or in the case of subjects under the age of 16 years, provide written assent (if required) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures.
Between 5 and 18 years of age, inclusive.
Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study.
Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study.
Willing to perform all study procedures as physically possible.

Exclusion Criteria:

Previous hematopoietic stem cell transplant (HSCT).
Has known hypersensitivity to BMN 110 or its excipients.
Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
Use of any investigational product or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
Concurrent disease or condition that would interfere with study participation or safety, including, but not limited to, symptomatic cervical spine instability.
Any condition that, in the view of the Principal Investigator (PI), places the subject at high risk of poor treatment compliance or of not completing the study.

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BMN 110

Arm Description

Within-patient Dose-Escalation

Outcomes

Primary Outcome Measures

Subject Incidence of Treatment Emergent AEs

The primary objective of the study was to evaluate the safety of weekly infusions of BMN 110 administered in escalating doses to subjects with MPS IVA. The safety variable incidence of TEAE is summarized.

Secondary Outcome Measures

Change From Baseline in 6MWT

Change from baseline in meters in 6-minute Walk Test. As a measure of endurance, a 6-minute walk test (6MWT) was performed according to the American Thoracic Society Guidelines. Patients were instructed to walk as far as possible in 6 minutes.

Change From Baseline in 3MSCT

Change from baseline in the 3-minute Stair Climb Test. Patients walked up stairs that have a railing, which could be used for support, for 3 minutes, with the number of stairs climbed recorded. The test result was the number of steps climbed per minute.

Percent Change From Baseline in uKS

Percent Change from baseline in Normalized Urine KS. The percent change was calculated (Week X value - baseline value)/baseline value *100%

Percent Change From Baseline in MVV

Percent Change from baseline in Maximum Voluntary Ventilation.

Percent Change From Baseline in FVC

Percent Change from baseline in Forced Vital Capacity.

Full Information

NCT ID

NCT00884949

First Posted

April 10, 2009

Last Updated

May 28, 2014

Sponsor

BioMarin Pharmaceutical

1. Study Identification

Unique Protocol Identification Number

NCT00884949

Brief Title

A Study to Evaluate the Safety, Tolerability and Efficacy of BMN 110 in Subjects With Mucopolysaccharidosis IVA

Official Title

A Phase 1/2, Multicenter, Open-label, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Efficacy of BMN 110 in Subjects With Mucopolysaccharidosis IVA (Morquio Syndrome)

Study Type

Interventional

2. Study Status

Record Verification Date

May 2014

Overall Recruitment Status

Completed

Study Start Date

April 2009 (undefined)

Primary Completion Date

February 2011 (Actual)

Study Completion Date

March 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

BioMarin Pharmaceutical

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This multicenter, open-label study is designed to assess safety, dose-response using pharmacokinetic (PK) and pharmacodynamic (PD) measures, and clinical efficacy of BMN 110 in subjects between 5 and 18 years of age, diagnosed with Mucopolysaccharidosis IVA (MPS IVA).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

MPS IV A

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BMN 110

Arm Type

Experimental

Arm Description

Within-patient Dose-Escalation

Intervention Type

Drug

Intervention Name(s)

BMN 110

Intervention Description

Subjects will receive a weekly 4- to 5-hour intravenous infusion of BMN 110 in 3 consecutive 12-week dosing intervals, using the following regimen: Weeks 1-12: 0.1 mg/kg/week Weeks 13-24: 1.0 mg/kg/week Weeks 25-36: 2.0 mg/kg/week Subjects who complete the 36-week Dose-Escalation Period will have the option to continue drug treatment for an additional 36 to 48 weeks. Subjects continuing on treatment after the Dose-Escalation period will receive weekly 4- to 5-hour intravenous infusions of BMN 110 at a dose of 1.0 mg/kg/week.

Primary Outcome Measure Information:

Title

Subject Incidence of Treatment Emergent AEs

Description

Time Frame

Entire Study, through week 84

Secondary Outcome Measure Information:

Title

Change From Baseline in 6MWT

Description

Time Frame

Baseline to Weeks 12, 24, 36, 48, 72

Title

Change From Baseline in 3MSCT

Description

Time Frame

Baseline to Weeks 12, 24, 36, 48, 72

Title

Percent Change From Baseline in uKS

Description

Percent Change from baseline in Normalized Urine KS. The percent change was calculated (Week X value - baseline value)/baseline value *100%

Time Frame

Baseline to Weeks 12, 24, 36, 72

Title

Percent Change From Baseline in MVV

Description

Percent Change from baseline in Maximum Voluntary Ventilation.

Time Frame

Baseline to Weeks 12, 24, 36, 72

Title

Percent Change From Baseline in FVC

Description

Percent Change from baseline in Forced Vital Capacity.

Time Frame

Baseline to Weeks 12, 24, 36, 72

10. Eligibility

Sex

All

Minimum Age & Unit of Time

5 Years

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Documented history of reduced GALNS activity relative to the normal range of the laboratory performing the assay, or documented result of molecular genetic testing confirming diagnosis of MPS IVA. Willing and able to provide written, signed informed consent, or in the case of subjects under the age of 16 years, provide written assent (if required) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures. Between 5 and 18 years of age, inclusive. Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study. Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Willing to perform all study procedures as physically possible. Exclusion Criteria: Previous hematopoietic stem cell transplant (HSCT). Has known hypersensitivity to BMN 110 or its excipients. Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study. Use of any investigational product or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments. Concurrent disease or condition that would interfere with study participation or safety, including, but not limited to, symptomatic cervical spine instability. Any condition that, in the view of the Principal Investigator (PI), places the subject at high risk of poor treatment compliance or of not completing the study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Celeste Decker, MD

Organizational Affiliation

BioMarin Pharmceutical Inc.

Official's Role

Study Director

Facility Information:

City

Birmingham

Country

United Kingdom

City

London

Country

United Kingdom

City

Manchester

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

29526614

Citation

Hendriksz C, Santra S, Jones SA, Geberhiwot T, Jesaitis L, Long B, Qi Y, Hawley SM, Decker C. Safety, immunogenicity, and clinical outcomes in patients with Morquio A syndrome participating in 2 sequential open-label studies of elosulfase alfa enzyme replacement therapy (MOR-002/MOR-100), representing 5 years of treatment. Mol Genet Metab. 2018 Apr;123(4):479-487. doi: 10.1016/j.ymgme.2018.02.011. Epub 2018 Feb 19.

Results Reference

derived

Links:

URL

http://www.bmrn.com

Description

BioMarin Pharmaceutical Inc. website

Learn more about this trial

A Study to Evaluate the Safety, Tolerability and Efficacy of BMN 110 in Subjects With Mucopolysaccharidosis IVA

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