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CompletedNCT00884949Updated Jun 30, 2014Results posted

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

A Phase 1/2 interventional study of BMN 110 in MPS IV A, sponsored by BioMarin Pharmaceutical. Completed at 3 sites in United Kingdom. Open to participants aged 5 Years to 18 Years. Per ClinicalTrials.gov, last updated 2014-06-30.

Sponsored by BioMarin Pharmaceutical · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
20
Allocation
Non-randomized
Ages
5 Years to 18 Years
Sex
All
01

Study 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).

02

Conditions studied

  • MPS IV A

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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
03

In context

Mucopolysaccharidoses

145 studies on the registry are indexed under Mucopolysaccharidoses; 11 are open to participants now.

This study's enrollment of 20 is above the median of 15 across 80 interventional studies indexed under Mucopolysaccharidoses.

Browse Mucopolysaccharidoses studies →

Lead sponsor

BioMarin Pharmaceutical is the lead sponsor of 110 studies on the registry; 13 are open to participants now.

Of its 17 completed or terminated interventional studies of FDA-regulated products, 12 (71%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
5 Years to 18 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
20 participants (actual)

Study arms

  • Experimental
    BMN 110

    Within-patient Dose-Escalation

    Drug: BMN 110

Interventions

  • DrugBMN 110

    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.

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Entire Study, through week 84

Secondary outcomes

  1. 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.

    Time frame: Baseline to Weeks 12, 24, 36, 48, 72

  2. 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.

    Time frame: Baseline to Weeks 12, 24, 36, 48, 72

  3. 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%

    Time frame: Baseline to Weeks 12, 24, 36, 72

  4. Percent Change From Baseline in MVV

    Percent Change from baseline in Maximum Voluntary Ventilation.

    Time frame: Baseline to Weeks 12, 24, 36, 72

  5. Percent Change From Baseline in FVC

    Percent Change from baseline in Forced Vital Capacity.

    Time frame: Baseline to Weeks 12, 24, 36, 72

07

Results

Posted Jun 30, 2014

Participant flow

Weeks 1-12: 0.1 mg/kg/Week
Participant flow — Weeks 1-12: 0.1 mg/kg/Week
MilestoneBMN 110
Started20
Completed18
Not completed2
Withdrew: Adverse event1
Withdrew: Withdrawal by subject1
Weeks 13-24: 1.0 mg/kg/Week
Participant flow — Weeks 13-24: 1.0 mg/kg/Week
MilestoneBMN 110
Started18
Completed18
Not completed0
Weeks 25-36: 2.0 mg/kg/Week
Participant flow — Weeks 25-36: 2.0 mg/kg/Week
MilestoneBMN 110
Started18
Completed18
Not completed0
Continuation Period
Participant flow — Continuation Period
MilestoneBMN 110
Started18
Completed18
Not completed0

Outcome measures

SecondaryChange 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.

Time frame:
Baseline to Weeks 12, 24, 36, 48, 72
Reported as:
Mean · meters
Change From Baseline in 6MWT
metersBMN 110
Week 12 Change from Baseline (n=19)-20.7 ± 85.95
Week 24 Change from Baseline (n=17)16.3 ± 71.74
Week 36 Change from Baseline (n=17)13.8 ± 63.25
Week 48 Change from Baseline (n=17)-4.8 ± 64.70
Week 72 Change from Baseline (n=17)4.0 ± 87.24
SecondaryChange 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.

Time frame:
Baseline to Weeks 12, 24, 36, 48, 72
Reported as:
Mean · steps/min
Change From Baseline in 3MSCT
steps/minBMN 110
Week 12 Change from Baseline (n=19)0.3 ± 14.07
Week 24 Change from Baseline (n=17)6.1 ± 8.66
Week 36 Change from Baseline (n=17)7.8 ± 13.69
Week 48 Change from Baseline (n=17)9.7 ± 14.42
Week 72 Change from Baseline (n=17)9.7 ± 13.91
SecondaryPercent 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%

Time frame:
Baseline to Weeks 12, 24, 36, 72
Reported as:
Mean · percentage of uKS
Percent Change From Baseline in uKS
percentage of uKSBMN 110
Week 12 Percent Change from Baseline (n=19)-23.2 ± 19.04
Week 24 Percent Change from Baseline (n=18)-27.9 ± 17.92
Week 36 Percent Change from Baseline (n=18)-40.6 ± 20.16
Week 72 Percent Change from Baseline (n=17)-32.2 ± 17.10
SecondaryPercent Change From Baseline in MVV

Percent Change from baseline in Maximum Voluntary Ventilation.

Time frame:
Baseline to Weeks 12, 24, 36, 72
Reported as:
Mean · percentage of MVV
Percent Change From Baseline in MVV
percentage of MVVBMN 110
Week 12 Percent Change from Baseline (n=14)9.9 ± 21.29
Week 24 Percent Change from Baseline (n=13)11.0 ± 21.48
Week 36 Percent Change from Baseline (n=14)10.5 ± 17.43
Week 72 Percent Change from Baseline (n=14)18.4 ± 20.77
SecondaryPercent Change From Baseline in FVC

Percent Change from baseline in Forced Vital Capacity.

Time frame:
Baseline to Weeks 12, 24, 36, 72
Reported as:
Mean · percentage of FVC
Percent Change From Baseline in FVC
percentage of FVCBMN 110
Week 12 Percent Change from Baseline (n=18)3.4 ± 10.85
Week 24 Percent Change from Baseline (n=16)0.2 ± 16.60
Week 36 Percent Change from Baseline (n=16)10.7 ± 20.82
Week 72 Percent Change from Baseline (n=16)12.5 ± 14.88
PrimarySubject 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.

Time frame:
Entire Study, through week 84
Reported as:
Number · participants
Subject Incidence of Treatment Emergent AEs
participants0.1 mg/kg/Week1.0 mg/kg/Week2.0 mg/kg/WeekContinuation PeriodEntire Study
Any AEs1818171720
Any Study Drug-Related AEs12107814
Any SAEs628614
Any Study Drug-Related SAEs21214
Any AEs During Infusion1513101517
Any SAEs During Infusion50116
Any AEs Causing Study Discontinuation10001
Any Study Drug-Related AE Causing Study Discont.10001
AEs Causing Permanent Study Drug Discont.10001
Drug-Related AE Causing Permanent StudyDrug Discon10001
Any SAEs Causing Study Discontinuation10001
Any SAEs Causing Permanent Study Drug Discont.10001
Study Drug-Related SAE Causing Study Discont.10001
StudyDrug-Related SAE Causing Permanent DrugDiscon10001
Death00000

Adverse events

Collected over Study Period, through 84 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
0.1 mg/kg/Week—6/20 (30%)18/20 (90%)
1.0 mg/kg/Week—2/18 (11.1%)18/18 (100%)
2.0 mg/kg/Week—8/18 (44.4%)16/18 (88.9%)
Continuation Period—6/18 (33.3%)17/18 (94.4%)
Entire Study—14/20 (70%)20/20 (100%)
Most frequent serious events
Showing 10 of 19
Most frequent serious events
Event0.1 mg/kg/Week1.0 mg/kg/Week2.0 mg/kg/WeekContinuation PeriodEntire Study
Knee deformityMusculoskeletal and connective tissue disorders1/200/182/182/185/20
Poor venous accessVascular disorders3/200/181/181/184/20
Catheterisation venousSurgical and medical procedures0/200/183/180/183/20
Lower respiratory tract infectionInfections and infestations0/200/181/181/182/20
Otitis mediaInfections and infestations2/200/180/180/182/20
Gait disturbanceGeneral disorders0/200/181/180/181/20
Infusion related reactionGeneral disorders0/200/181/181/181/20
Abscess limbInfections and infestations0/201/180/180/181/20
Catheter site infectionInfections and infestations0/200/181/180/181/20
Implant site infectionInfections and infestations0/200/181/180/181/20
Most frequent other events
Showing 10 of 158
Most frequent other events
Event0.1 mg/kg/Week1.0 mg/kg/Week2.0 mg/kg/WeekContinuation PeriodEntire Study
PyrexiaGeneral disorders6/209/185/1810/1814/20
VomitingGastrointestinal disorders2/207/184/1812/1813/20
CoughRespiratory, thoracic and mediastinal disorders1/205/183/1810/1813/20
Pain in extremityMusculoskeletal and connective tissue disorders4/203/181/184/1810/20
HeadacheNervous system disorders4/202/181/186/189/20
Abdominal pain upperGastrointestinal disorders4/201/183/184/188/20
NasopharyngitisInfections and infestations2/203/181/184/188/20
ArthralgiaMusculoskeletal and connective tissue disorders3/203/180/184/188/20
DiarrhoeaGastrointestinal disorders0/202/183/181/186/20
Nuclear magnetic resonance imagingInvestigations1/202/180/184/186/20

Baseline characteristics

Age, Continuous
Age, Continuous(years)BMN 110
Mean8.0 ± 2.89
Age, Customized
Age, Customized(participants)BMN 110
>=4 to <8 years10
>=8 to <10 years6
>=10 to <=18 years4
Sex: Female, Male
Sex: Female, Male(Participants)BMN 110
Female8
Male12
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)BMN 110
Hispanic or Latino0
Not Hispanic or Latino20
Unknown or Not Reported0
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)BMN 110
American Indian or Alaska Native0
Asian9
Native Hawaiian or Other Pacific Islander0
Black or African American0
White9
Other2
Region of Enrollment
Region of Enrollment(participants)BMN 110
United Kingdom20
08

Study locations

3 sites
  • Birmingham, United Kingdom
  • London, United Kingdom
  • Manchester, United Kingdom
09

References and documents

Publications

  • 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. PubMed 29526614 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 30, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00884949
Lead sponsor
BioMarin Pharmaceutical
Responsible party
Sponsor
First posted
Apr 21, 2009
Start date
Apr 2009
Primary completion
Feb 2011
Completion
Mar 2011
Results posted
Jun 30, 2014
Last update
Jun 30, 2014

Study contacts

Celeste Decker, MD
study director · BioMarin Pharmceutical Inc.

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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