Mucopolysaccharidosis IVAPhase 2NCT01697319

Efficacy and Safety Study of BMN 110 for Morquio A Syndrome Patients Who Have Limited Ambulation

A Phase 2 study testing BMN 110 in people with Mucopolysaccharidosis IVA and Morquio A Syndrome, run by BioMarin Pharmaceutical at 7 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The primary objective of this study is to evaluate the effect of 2.0 mg/kg/week BMN 110 in a patient population that has limited ambulation, in a period of up to 144 weeks. Read more about this study

Who is it for?: Ages 5 years and older
Conditions the study is for: Mucopolysaccharidosis IVA, Morquio A Syndrome, MPS IVA
What is being tested?: BMN 110
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 7 sitesin 3 countries
Study dates: Aug 2012to Oct 2014
Phase: Phase 2
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

Is willing and able to provide written, signed informed consent (or their legally authorized representative) after the nature of the study has been explained and prior to performance of any research-related procedure. Patients who do not meet country and local age requirements for informed consent must be willing and able to provide written assent after the nature of the study has been explained and prior to performance of any research-related procedure.
Has 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.
Is ≥ 5 years of age.
If sexually active, is willing to use an acceptable method of contraception while participating in the study.
Females of childbearing potential must have a negative pregnancy test at the Screening Visit and be willing to have additional pregnancy tests during the study.
Is willing and able to perform all study procedures as physically possible.

Who cannot join

Is able to walk farther than a specified distance as assessed by the 6MWT.
Has previous hematopoietic stem cell transplant (HSCT).
Has received previous treatment with BMN 110.
Has a known hypersensitivity to any of the components of BMN 110.
Has had major surgery within 3 months prior to study entry or is planning to have a major surgery during the first 24 weeks of the study.
Has used any other investigational product or investigational medical device within 30 days prior to the Screening Visit or requires any investigational agent prior to completion of all scheduled study assessments.

Show all 9Show fewer

Is pregnant or breastfeeding at the Screening Visit or planning to become pregnant (self or partner) at any time during the study.
Has a concurrent disease or condition, including but not limited to symptomatic cervical spine instability or severe cardiac disease or complete paralysis due to a spinal cord injury (defined as an inability to move arms and legs), that would interfere with study participation or safety 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

7 sites in 3 countries.

Country

City, postcode or hospital

7 sites in 3 countries

United Kingdom3 sites

NIHR/Wellcome Trust Birmingham CRF, Queen Elizabeth Hospital
Birmingham
Central Manchester University Hospitals NHS Foundation Trust
Manchester
Salford Royal NHS Foundation Trust
Salford

Other trials in United Kingdom

United States2 sites

Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois
Children's Hospital & Research Center Oakland
Oakland, California

Other trials in United States

Germany2 sites

Universitätsklinikum Hamburg
Hamburg
University Medical Center Mainz, Center of Pediatric and Adolescent Medicine Villa Metabolica
Mainz

Other trials in Germany

About this study

Official title: A Phase 2, Open-label, Multinational Study to Evaluate the Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome) Who Have Limited Ambulation

The primary objective of this study is to evaluate the effect of 2.0 mg/kg/week BMN 110 in a patient population that has limited ambulation, in a period of up to 144 weeks.

Read the detailed description

Effect is defined by the following key domains:

Upper extremity function and dexterity
Mobility

Conditions: Mucopolysaccharidosis IVA, Morquio A Syndrome, MPS IVA
Being tested: BMN 110
Keywords: Mucopolysaccharidosis IVA Type A, MPS IVA 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, MOR-006, CPET, Limited ambulation, Grip/ Pinch
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 110Drug
Also called N-acetylgalactosamine-6-sulfatase, N-acetylgalactosamine-6-sulfate, sulfatase, galactose-6-sulfatase
Drug will be delivered through a 4 hour (approximate) IV infusion at a dosage amount of 2.0 mg/kg/week for up to 144 weeks of treatment.

Study groups in NCT01697319
Study group	Role	What they receive
BMN 110 at 2.0 mg/kg/week	Experimental	Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for up to 144 weeks. Receives: Drug: BMN 110

What is being measured

The primary outcome is the main question the study is designed to answer.

Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT)
FDT assesses the ability to use the hand in daily tasks. The test involves turning 16 wooden pegs over as quickly as possible on a hardwood pegboard with one hand requiring a three-jaw chuck prehension pattern between the fingers and thumb within a two-minute time limit. Hand function is evaluated by how fast a patient can turn over pegs in the given time limit, i.e. speed (number of pegs/minute).
Measured: Up to 96 weeks
Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT)
A grip-strength dynamometer and a pinch meter were used to measure grip strength and pinch strength. The results report change from baseline in strength for dominant and non-dominant hand in a forearm and wrist supported position.
Measured: Up to 96 weeks
Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT)
The timed 25-Foot Walk Test (25FWT) is an assessment of mobility and performance of leg function. The patient was instructed to walk a marked 25-foot course as quickly as possible in a time limit of 3 minutes and immediately walk back the same distance when reaching one end.The patient is allowed to use any ambulation method to move. The outcome measures the speed (feet / min) of moving.
Measured: Up to 96 weeks

Secondary outcomes (1)

Percent Change From Baseline in Normalized Urine Keratan Sulfate (uKS)
Urinary keratan sulfate and urinary creatinine were measured through quantitative analysis. uKS is normalized to creatinine.
Measured: Up to 96 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2012Oct 2014

First posted2 Oct 2012 (estimated)
Study startAug 2012
Primary completionOct 2014
Study completionOct 2014

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.
Other trials for Mucopolysaccharidosis IVAStudies 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 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01697319
Sponsor's protocol ID: MOR-006
Other IDs: 2011-005703-33
Status last verified: Dec 2015
First submitted: 17 Sep 2012
Last updated: 12 Jan 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Cardiac Structure and Function in MPS
MPS I, MPS IV A
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome
RecruitingObservational study
Non-invasive Functional Assessment and Pathogenesis of Morquio A
Mucopolysaccharidosis IV Type A, Morquio A Syndrome
RecruitingObservational study
Registry of Patients Diagnosed With Lysosomal Storage Diseases
Mucopolysaccharidosis I, Mucopolysaccharidosis II
RecruitingPhase 1
PEARL (PrEnAtal Enzyme Replacement Therapy for Lysosomal Storage Disorders)
MPS I, MPS II

All Mucopolysaccharidosis IVA trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, Open-label, Multinational Study to Evaluate the Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome) Who Have Limited Ambulation
ClinicalTrials.gov ID: NCT01697319
Acronym / sponsor ID: MOR-006
Conditions: Mucopolysaccharidosis IVA, Morquio A Syndrome, MPS IVA
Keywords: Mucopolysaccharidosis IVA Type A, MPS IVA Type A, Mucopolysaccharidosis IVA, MPS IVA, Morquio A Syndrome, Lysosomal Storage Disorder, LSD, N-acetylgalactosamine-6-sulfatase
Phase: Phase 2
Study type: Interventional
Recruitment status: Terminated
Enrolment: 16 participants (actual)
Lead sponsor: BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
Study start: Aug 2012
Primary completion: Oct 2014 (actual)
Study completion: Oct 2014 (actual)
First posted: 2 Oct 2012 (estimated)
Results: Posted 12 Jan 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The primary objective of this study is to evaluate the effect of 2.0 mg/kg/week BMN 110 in a patient population that has limited ambulation, in a period of up to 144 weeks.

Detailed description

Effect is defined by the following key domains:

Upper extremity function and dexterity
Mobility

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
BMN 110 at 2.0 mg/kg/week	Experimental	Drug: BMN 110Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for up to 144 weeks.

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)

Is willing and able to provide written, signed informed consent (or their legally authorized representative) after the nature of the study has been explained and prior to performance of any research-related procedure. Patients who do not meet country and local age requirements for informed consent must be willing and able to provide written assent after the nature of the study has been explained and prior to performance of any research-related procedure.
Has 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.
Is ≥ 5 years of age.
If sexually active, is willing to use an acceptable method of contraception while participating in the study.
Females of childbearing potential must have a negative pregnancy test at the Screening Visit and be willing to have additional pregnancy tests during the study.

Key exclusion criteria (9 listed)

Is able to walk farther than a specified distance as assessed by the 6MWT.
Has previous hematopoietic stem cell transplant (HSCT).
Has received previous treatment with BMN 110.
Has a known hypersensitivity to any of the components of BMN 110.
Has had major surgery within 3 months prior to study entry or is planning to have a major surgery during the first 24 weeks of 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 110Also: N-acetylgalactosamine-6-sulfatase, N-acetylgalactosamine-6-sulfate, sulfatase, galactose-6-sulfataseDrug will be delivered through a 4 hour (approximate) IV infusion at a dosage amount of 2.0 mg/kg/week for up to 144 weeks of treatment.	Drug	BMN 110 at 2.0 mg/kg/week

Primary outcome

Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT)
Time frame: Up to 96 weeks
FDT assesses the ability to use the hand in daily tasks. The test involves turning 16 wooden pegs over as quickly as possible on a hardwood pegboard with one hand requiring a three-jaw chuck prehension pattern between the fingers and thumb within a two-minute time limit. Hand function is evaluated by how fast a patient can turn over pegs in the given time limit, i.e. speed (number of pegs/minute).
Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT)
Time frame: Up to 96 weeks
A grip-strength dynamometer and a pinch meter were used to measure grip strength and pinch strength. The results report change from baseline in strength for dominant and non-dominant hand in a forearm and wrist supported position.
Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT)
Time frame: Up to 96 weeks
The timed 25-Foot Walk Test (25FWT) is an assessment of mobility and performance of leg function. The patient was instructed to walk a marked 25-foot course as quickly as possible in a time limit of 3 minutes and immediately walk back the same distance when reaching one end.The patient is allowed to use any ambulation method to move. The outcome measures the speed (feet / min) of moving.

1 secondary outcome

Percent Change From Baseline in Normalized Urine Keratan Sulfate (uKS)
Time frame: Up to 96 weeks

Results and safety

Results posted to the registry on 12 Jan 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
BMN 110 at 2.0 mg/kg/Week	16	15

Primary outcome: Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT)

Time frame: Up to 96 weeks. Mean (Standard Deviation). Unit: % of change

Measure	BMN 110 at 2.0 mg/kg/Week n = 15
Dominant Hand Wk 24 % Chg from Baseline	1.8 (45.60)
Dominant Hand Wk 48 % Chg from Baseline	23.1 (53.88)
Dominant Hand Wk 72 % Chg from Baseline	37.2 (54.94)
Dominant Hand Wk 96 % Chg from Baseline	22.5 (42.21)
Non-Dominant Hand Wk 24 % Chg from Baseline	13.8 (32.54)
Non-Dominant Hand Wk 48 % Chg from Baseline	6.0 (35.78)
Non-Dominant Hand Wk 72 % Chg from Baseline	49.3 (126.26)
Non-Dominant Hand Wk 96 % Chg from Baseline	-2.0 (2.83)

Population analysed: Modified ITT Population

Primary outcome: Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT)

Time frame: Up to 96 weeks. Mean (Standard Deviation). Unit: kg

Measure	BMN 110 at 2.0 mg/kg/Week n = 15
Grip Dominant Hand Wk 24 Chg from Baseline	0.1 (0.89)
Grip Dominant Hand Wk 48 Chg from Baseline	-0.3 (0.90)
Grip Dominant Hand Wk 72 Chg from Baseline	-0.1 (0.33)
Grip Dominant Hand Wk 96 Chg from Baseline	0.3 (0.23)
Grip Non-Dominant Hand Wk24 Chg from Baseline	-0.0 (0.70)
Grip Non-Dominant Hand Wk 48 Chg from Baseline	-0.1 (0.66)
Grip Non-Dominant Hand Wk 72 Chg from Baseline	0.1 (0.79)
Grip Non-Dominant Hand Wk 96 Chg from Baseline	0.4 (0.87)

Population analysed: Modified ITT Population

Primary outcome: Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT)

Time frame: Up to 96 weeks. Mean (Standard Deviation). Unit: % of change

Measure	BMN 110 at 2.0 mg/kg/Week n = 15
Wk 24 % Change from Baseline Two Attempts Combined	95.7 (142.37)
Wk 48 % Change from Baseline Two Attempts Combined	53.5 (102.74)
Wk 72 % Change from Baseline Two Attempts Combined	48.3 (145.01)
Wk 96 % Change from Baseline Two Attempts Combined	NA (NA)

Population analysed: Modified ITT Population

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Study Period. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
BMN 110 at 2.0 mg/kg/Week	7 of 15 (46.7%)	15 of 15 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Mucopolysaccharidosis IVA

RecruitingObservational study
Cardiac Structure and Function in MPS
MPS I, MPS IV A
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome
RecruitingObservational study
Non-invasive Functional Assessment and Pathogenesis of Morquio A
Mucopolysaccharidosis IV Type A, Morquio A Syndrome
RecruitingObservational study
Registry of Patients Diagnosed With Lysosomal Storage Diseases
Mucopolysaccharidosis I, Mucopolysaccharidosis II
RecruitingPhase 1
PEARL (PrEnAtal Enzyme Replacement Therapy for Lysosomal Storage Disorders)
MPS I, MPS II

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.

Celeste Decker, M.D. study director

BioMarin Pharmaceutical

7 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BMN 110 in people with Mucopolysaccharidosis IVA and Morquio A Syndrome, run by BioMarin Pharmaceutical at 7 sites in 3 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 9 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: stopped early, as of the sponsor's last update on 12 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United Kingdom, United States, Germany. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 12 Jan 2016). 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?

Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT) (time frame: Up to 96 weeks). The study lists 3 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 NCT01697319.

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 12 Jan 2016.