MPS IV APhase 3NCT01275066
A Double-Blind Study to Evaluate the Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
A Phase 3 study testing BMN 110 Weekly and BMN 110 Every Other Week in people with MPS IV A, run by BioMarin Pharmaceutical at 28 sites in 17 countries.
Trial summary
This Phase 3 study will evaluate the efficacy and safety of 2.0 mg/kg/week BMN 110 and 2.0 mg/kg/every other week BMN 110 in patients with mucopolysaccharidosis IVA (Morquio A Syndrome). There is currently no standard accepted treatment for MPS IVA other than supportive care. Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- MPS IV A
- What is being tested?
- BMN 110 Weekly and BMN 110 Every Other Week
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 177 participants
- Where
- 28 sitesin 17 countries
- Study dates
- Feb 2011to Aug 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- At least 5 years of age.
- Documented clinical diagnosis of MPS IVA based on clinical signs and symptoms of MPS IVA and documented reduced fibroblast or leukocyte GALNS enzyme activity or genetic testing confirming diagnosis of MPS IVA.
- Willing and able to provide written, signed informed consent, or in the case of patients under the age of 18 (or 16 years, depending on the region), 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.
- Must meet the study entrance requirements for the 6-minute walk test.
- Sexually active patients 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.
Who cannot join
- Previous hematopoietic stem cell transplant (HSCT).
- Previous treatment with BMN 110.
- Has known hypersensitivity to any of the components of BMN 110.
- Major surgery within 3 months prior to study entry or planned major surgery during the 24-week treatment period.
- 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, 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 safety as determined by the Investigator.
- 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.
Trial locations and contacts
28 sites in 17 countries.
28 sites in 17 countries
United States6 sites
Study site
Chicago, Illinois
Study site
New York, New York
Study site
Oakland, California
Study site
Seattle, Washington
Study site
Washington D.C., District of Columbia
Study site
Wilmington, Delaware
United Kingdom3 sites
Study site
Birmingham
Study site
London
Study site
Manchester
About this study
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multinational Clinical Study to Evaluate the Efficacy and Safety of 2.0 mg/kg/Week and 2.0 mg/kg/Every Other Week BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
This Phase 3 study will evaluate the efficacy and safety of 2.0 mg/kg/week BMN 110 and 2.0 mg/kg/every other week BMN 110 in patients with mucopolysaccharidosis IVA (Morquio A Syndrome).
There is currently no standard accepted treatment for MPS IVA other than supportive care. Enzyme replacement therapy (ERT) may be a potential new treatment option for MPS IVA patients. BMN 110 is administered to MPS IVA patients by IV infusion, allowing cellular uptake by the mannose-6-phosphate receptor and transportation to the lysosomes.
This enzyme uptake into the lysosomes is hypothesized to promote increased catabolism of keratan sulfate (KS) in tissue macrophages, hyaline cartilage, other connective tissues, and heart valve, and reduce the progressive accumulation of KS which is responsible for the clinical manifestations of the disorders.
- Conditions
- MPS IV A
- Being tested
- BMN 110 Weekly, Placebo, BMN 110 Every Other Week
- 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
- Medical subject headings
- Mucopolysaccharidosis IV, Lysosomal Storage Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMN 110 WeeklyDrug
Also called recombinant human N-acetylgalactosamine-6-sulfatase, rhGALNS
BMN 110 Weekly: Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours once a week.
PlaceboDrug
Intravenous infusion of placebo solution at a volume equivalent to that needed for 2.0 mg/kg dose of BMN 110 administered over a period of approximately 4 hours once a week.
BMN 110 Every Other WeekDrug
Also called recombinant human N-acetylgalactosamine-6-sulfatase, rhGALNS
BMN 110 Every Other Week: 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 infusions of placebo on alternating weeks.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| BMN 110 Weekly | Experimental | Not described Receives: Drug: BMN 110 Weekly |
| BMN 110 Every Other Week | Experimental | Not described Receives: Drug: BMN 110 Every Other Week |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Endurance as Measured by the 6-minute Walk Test
Measured: Baseline to Week 24
Secondary outcomes (2)
Change From Baseline in Endurance as Measured by the 3-minute Stair Climb Test
Measured: Baseline to Week 24
Percent Change From Baseline in Urine Keratan Sulfate Normalized for Urine Creatinine
Measured: Baseline to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2011 (estimated)
- Study startFeb 2011
- Primary completionAug 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MPS IV AStudies of the same condition, open and under way.
- More trials run by BioMarin PharmaceuticalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 177 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioMarin Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Debra Lounsbury, Study director, BioMarin Pharmaceutical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01275066
- Sponsor's protocol ID
- MOR-004
- Other IDs
- 2010-020198-18, 10/H1306/87, 18972/0213/001-0001, 2011_038#B201129, 145240, 2011-01-09, 20110012889, 0999935174
- Status last verified
- Jun 2014
- First submitted
- 10 Jan 2011
- Last updated
- 7 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Schweighardt B, Tompkins T, Lau K, Jesaitis L, Qi Y, Musson DG, Farmer P, Haller C, Shaywitz AJ, Yang K, O'Neill CA. Immunogenicity of Elosulfase Alfa, an Enzyme Replacement Therapy in Patients With Morquio A Syndrome: Results From MOR-004, a Phase III Trial. Clin Ther. 2015 May 1;37(5):1012-1021.e6. doi: 10.1016/j.clinthera.2014.11.005. Epub 2014 Dec 6.
PubMed 25487082
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multinational Clinical Study to Evaluate the Efficacy and Safety of 2.0 mg/kg/Week and 2.0 mg/kg/Every Other Week BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
- ClinicalTrials.gov ID
- NCT01275066
- Acronym / sponsor ID
- MOR-004
- Conditions
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 177 participants (actual)
- Lead sponsor
- BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- Feb 2011
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 12 Jan 2011 (estimated)
- Results
- Posted 15 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase 3 study will evaluate the efficacy and safety of 2.0 mg/kg/week BMN 110 and 2.0 mg/kg/every other week BMN 110 in patients with mucopolysaccharidosis IVA (Morquio A Syndrome).
There is currently no standard accepted treatment for MPS IVA other than supportive care. Enzyme replacement therapy (ERT) may be a potential new treatment option for MPS IVA patients. BMN 110 is administered to MPS IVA patients by IV infusion, allowing cellular uptake by the mannose-6-phosphate receptor and transportation to the lysosomes.
This enzyme uptake into the lysosomes is hypothesized to promote increased catabolism of keratan sulfate (KS) in tissue macrophages, hyaline cartilage, other connective tissues, and heart valve, and reduce the progressive accumulation of KS which is responsible for the clinical manifestations of the disorders.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo |
| BMN 110 Weekly | Experimental | Drug: BMN 110 Weekly |
| BMN 110 Every Other Week | Experimental | Drug: BMN 110 Every Other Week |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- At least 5 years of age.
- Documented clinical diagnosis of MPS IVA based on clinical signs and symptoms of MPS IVA and documented reduced fibroblast or leukocyte GALNS enzyme activity or genetic testing confirming diagnosis of MPS IVA.
- Willing and able to provide written, signed informed consent, or in the case of patients under the age of 18 (or 16 years, depending on the region), 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.
- Must meet the study entrance requirements for the 6-minute walk test.
- Sexually active patients must be willing to use an acceptable method of contraception while participating in the study.
Key exclusion criteria (8 listed)
- Previous hematopoietic stem cell transplant (HSCT).
- Previous treatment with BMN 110.
- Has known hypersensitivity to any of the components of BMN 110.
- Major surgery within 3 months prior to study entry or planned major surgery during the 24-week treatment period.
- Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BMN 110 WeeklyAlso: recombinant human N-acetylgalactosamine-6-sulfatase, rhGALNSBMN 110 Weekly: 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 |
| PlaceboIntravenous infusion of placebo solution at a volume equivalent to that needed for 2.0 mg/kg dose of BMN 110 administered over a period of approximately 4 hours once a week. | Drug | Placebo |
| BMN 110 Every Other WeekAlso: recombinant human N-acetylgalactosamine-6-sulfatase, rhGALNSBMN 110 Every Other Week: 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 infusions of placebo on alternating weeks. | Drug | BMN 110 Every Other Week |
Primary outcome
Change From Baseline in Endurance as Measured by the 6-minute Walk Test
Time frame: Baseline to Week 24
2 secondary outcomes
Change From Baseline in Endurance as Measured by the 3-minute Stair Climb Test
Time frame: Baseline to Week 24
Percent Change From Baseline in Urine Keratan Sulfate Normalized for Urine Creatinine
Time frame: Baseline to Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25487082Schweighardt B, Tompkins T, Lau K, Jesaitis L, Qi Y, Musson DG, Farmer P, Haller C, Shaywitz AJ, Yang K, O'Neill CA. Immunogenicity of Elosulfase Alfa, an Enzyme Replacement Therapy in Patients With Morquio A Syndrome: Results From MOR-004, a Phase III Trial. Clin Ther. 2015 May 1;37(5):1012-1021.e6. doi: 10.1016/j.clinthera.2014.11.005. Epub 2014 Dec 6.
- BioMarin Pharmaceutical Inc. websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Debra Lounsbury study director
BioMarin Pharmaceutical
28 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing BMN 110 Weekly and BMN 110 Every Other Week in people with MPS IV A, run by BioMarin Pharmaceutical at 28 sites in 17 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in United States, Canada, United Kingdom, Brazil, France and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Endurance as Measured by the 6-minute Walk Test (time frame: Baseline to Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01275066, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2014.