Mucopolysaccharidosis IV APhase 3NCT01415427
Long-Term Efficacy and Safety Extension Study 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 Mucopolysaccharidosis IV A and Morquio A Syndrome, run by BioMarin Pharmaceutical at 43 sites in 20 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Mucopolysaccharidosis IV A, Morquio A Syndrome, MPS IVA
- What is being tested?
- BMN 110 - Weekly and BMN 110 - Every Other Week
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 173 participants
- Where
- 43 sitesin 20 countries
- Study dates
- Jul 2011to 16 Jun 2016
- 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
- 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.
Who cannot join
- 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.
Trial locations and contacts
43 sites in 20 countries.
43 sites in 20 countries
United States10 sites
Study site
Chicago, Illinois
Study site
Honolulu, Hawaii
Study site
New York, New York
Study site
Oakland, California
Study site
Orange, California
Study site
Orlando, Florida
Study site
Phoenix, Arizona
Study site
Seattle, Washington
Study site
Washington D.C., District of Columbia
Study site
Wilmington, Delaware
United Kingdom7 sites
Study site
Belfast, BT9 7AB
Study site
Birmingham, B15 2TH
Study site
Birmingham, B4 6NH
Study site
London, NW3 2PF
Study site
London, WC1N 3BG
Study site
London, WC1N 3JH
Study site
Manchester, M13 9WL
France4 sites
Study site
Lyon
Study site
Marseille
Study site
Paris, Cedex 12
Study site
Paris, Cedex 15
Brazil3 sites
Study site
Campina Grande
Study site
Porto Alegre
Study site
Rio de Janeiro
About this study
Official title: 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).
Read the 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
- Conditions
- Mucopolysaccharidosis IV A, Morquio A Syndrome, MPS IVA
- Being tested
- BMN 110 - Weekly, 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 N-acetylgalactosamine-6-sulfatase, N-acetylgalactosamine-6-sulfate sulfatase, galactose-6-sulfatase, GALNS
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 WeekDrug
Also called N-acetylgalactosamine-6-sulfatase, N-acetylgalactosamine-6-sulfate sulfatase, galactose-6-sulfatase, GALNS
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.
| Study group | Role | What they receive |
|---|---|---|
| BMN 110 Weekly | Experimental | 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. Receives: Drug: BMN 110 - Weekly |
| BMN 110 Every Other Week | Experimental | 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. 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 6-minute Walk (6MW) Test - ITT
Efficacy was assessed by changes from baseline in 6-minute walk test
Measured: 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
Measured: Baseline to week 168
Secondary outcomes (4)
Change From Baseline in 3-minute Stair Climb Test - ITT
Efficacy was assessed by changes from baseline in 3-minute stair climb test.
Measured: 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.
Measured: 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.)
Measured: 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.)
Measured: Baseline to week 168
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2011 (estimated)
- Study startJul 2011
- Primary completion16 Jun 2016
- Study completion16 Jun 2016
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 (3)Papers the sponsor has linked to this study.
- Other trials for Mucopolysaccharidosis 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
- 173 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
- NCT01415427
- Sponsor's protocol ID
- MOR-005
- Status last verified
- Apr 2017
- First submitted
- 8 Aug 2011
- Last updated
- 21 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 29248359Hughes 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.
PubMed 28535791Long 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.
PubMed 27955919
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Multinational, Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
- ClinicalTrials.gov ID
- NCT01415427
- Acronym / sponsor ID
- MOR-005
- Conditions
- Mucopolysaccharidosis IV A, Morquio A Syndrome, MPS IVA
- 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
- 173 participants (actual)
- Lead sponsor
- BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- Jul 2011
- Primary completion
- 16 Jun 2016 (actual)
- Study completion
- 16 Jun 2016 (actual)
- First posted
- 12 Aug 2011 (estimated)
- Results
- Posted 19 May 2017
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 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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BMN 110 Weekly | Experimental | Drug: BMN 110 - WeeklyBMN 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. |
| BMN 110 Every Other Week | Experimental | Drug: BMN 110 - Every Other WeekBMN 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. |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
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: N-acetylgalactosamine-6-sulfatase, N-acetylgalactosamine-6-sulfate sulfatase, galactose-6-sulfatase, GALNSIn 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. | Drug | BMN 110 Weekly |
| BMN 110 - Every Other WeekAlso: N-acetylgalactosamine-6-sulfatase, N-acetylgalactosamine-6-sulfate sulfatase, galactose-6-sulfatase, GALNSIn 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. | Drug | BMN 110 Every Other Week |
Primary outcome
Change From Baseline in 6-minute Walk (6MW) Test - ITT
Time frame: Baseline to week 168
Efficacy was assessed by changes from baseline in 6-minute walk test
Change From Baseline in 6-minute Walk (6MW) Test - MPP
Time frame: Baseline to week 168
Efficacy was assessed by changes from baseline in 6-minute walk test
4 secondary outcomes
Change From Baseline in 3-minute Stair Climb Test - ITT
Time frame: Baseline to week 168
Change From Baseline in 3-minute Stair Climb Test - MPP
Time frame: Baseline to week 168
Change From Baseline in Urine Keratan Sulfate - ITT
Time frame: Baseline to week 168
Change From Baseline in Urine Keratan Sulfate - MPP
Time frame: Baseline to week 168
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29248359Hendriksz 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.
- Derived from this study: PubMed 28535791Hughes 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.
- Derived from this study: PubMed 27955919Long 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.
Related trials for Mucopolysaccharidosis IV A
RecruitingObservational study
Cardiac Structure and Function in MPS
MPS I, MPS IV A
Not yet recruitingPhase 3
A Study to Investigate the Safety, Pharmacokinetics (PK), and Efficacy of Garetosmab in Children and Adolescents With Fibrodysplasia Ossificans Progressiva (FOP)
Fibrodysplasia Ossificans Progressiva, FOP
Enrolling by invitationObservational study
ScreenPlus: A Comprehensive, Flexible, Multi-disorder Newborn Screening Program
Acid Sphingomyelinase Deficiency, Ceroid Lipofuscinosis, Neuronal, 2
Enrolling by invitationPhase 2/3
An Interventional Study of Infigratinib in Children With Hypochondroplasia
Hypochondroplasia
RecruitingPhase 2
Interventional Study of Infigratinib in Children < 3 Years Old With Achondroplasia (ACH)
Achondroplasia
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
43 sites in 20 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 Mucopolysaccharidosis IV A and Morquio A Syndrome, run by BioMarin Pharmaceutical at 43 sites in 20 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 4 inclusion and 5 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 21 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 43 sites in United States, United Kingdom, France, Brazil, Canada and 15 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. 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 19 May 2017). 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 6-minute Walk (6MW) Test - ITT (time frame: Baseline to week 168). The study lists 2 primary outcomes in all. 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 NCT01415427, which also lists 3 linked publications.
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 21 Jul 2021.