Mucopolysaccharidosis IVAPhase 2NCT01609062
Safety and Exercise Study of Two Doses of BMN 110 for Morquio A Syndrome
A Phase 2 study testing BMN 110 in people with Mucopolysaccharidosis IVA and Morquio A Syndrome, run by BioMarin Pharmaceutical at 11 sites in 4 countries.
Trial summary
The primary objective of this study was to evaluate the safety of a 2.0 mg/kg/week and a 4.0 mg/kg/week of BMN 110 in patients with Morquio A syndrome for up to 196 weeks. Secondary objectives were to investigate the effect of the two doses on exercise capacity for up to 196 weeks. Read more about this study
- Who is it for?
- Ages 7 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
- 25 participants
- Where
- 11 sitesin 4 countries
- Study dates
- Apr 2012to Nov 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 7 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 patient's legally authorized representative) after the nature of the study has been explained and prior to performance of any research- related procedure. Also, patients who do not meet country and local age requirements for informed consent must be willing and able to 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 performance of any research-related procedure.
- Has documented clinical diagnosis of Morquio A Syndrome (MPS IVA) based on clinical signs and symptoms of MPS IVA and documented reduced fibroblast or leukocyte N-acetylgalactosamine-6-sulfatase (GALNS) enzyme activity or genetic testing confirming diagnosis of MPS IVA.
- Is at least 7 years of age
- Is able to walk ≥ 200 meters as assessed by the 6-minute Walk Test (6MWT)
- If sexually active, is 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 the Screening Visit and be willing to have additional pregnancy tests during the study
- Is willing and able to perform all study procedures, including cardiopulmonary exercise testing (CPET)
Who cannot join
- Inability to perform an exercise test due to limited mobility
- Body weight greater than 95 kg at Screening
- Severe, untreated sleep apnea as measured during Screening with a home sleep testing device
- Patients with a history of, or current condition of sleep apnea or sleep disordered breathing under adequate treatment may be enrolled if approved by the medical monitor.
- Requirement for supplemental oxygen
- Use of ventilator assistance in the 3 months prior to study entry
Show all 17Show fewer
- Use of positive airway pressure (continuous positive airway pressure, CPAP, or bilevel airway pressure) for treatment of sleep apnea or sleep disordered breathing is allowed if settings have been stable for at least 1 month prior to study entry, and is approved by the medical monitor.
- 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 previous hematopoietic stem cell transplant (HSCT)
- Has received previous treatment with BMN 110
- Has a known hypersensitivity to BMN 110 or its excipients
- Has had major surgery within 3 months prior to study entry or is planning to have a major surgery during the duration of the study
- Use of any other investigational product (IP) or investigational medical device within 30 days prior to the beginning of the Screening Period or requires any investigational agent prior to completion of all scheduled study assessments
- Is pregnant or breastfeeding during the Screening Period or planning to become pregnant (self or partner) at any time during the study
- Has a concurrent disease or condition that may interfere with study participation or safety, and/or ability to perform study procedures as determined by the Investigator
- Has any condition that, in the view of the Investigator, poses a safety risk to the patient
- 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
11 sites in 4 countries.
11 sites in 4 countries
United States4 sites
Study site
Chicago, Illinois
Study site
Houston, Texas
Study site
New York, New York
Study site
Oakland, California
Canada4 sites
Study site
Calgary, Alberta
Study site
Montreal, Quebec
Study site
Sherbrook, Quebec
Study site
Toronto, Ontario
United Kingdom2 sites
Study site
Belfast, Northern Ireland
Study site
Manchester
About this study
Official title: A Randomized, Double-Blind, Pilot Study of the Safety and Physiological Effects of Two Doses of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
The primary objective of this study was to evaluate the safety of a 2.0 mg/kg/week and a 4.0 mg/kg/week of BMN 110 in patients with Morquio A syndrome for up to 196 weeks. Secondary objectives were to investigate the effect of the two doses on exercise capacity for up to 196 weeks. In addition, the pharmacokinetic (PK) parameters of both doses of BMN 110 was assessed.
- 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-008, CPET, MST, muscle strength test, physiological effect
- 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
Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for up to 192 weeks.
BMN 110Drug
Also called N-acetylgalactosamine-6-sulfatase, N-acetylgalactosamine-6-sulfate, sulfatase, galactose-6-sulfatase
Weekly IV infusions of BMN 110 at 4.0 mg/kg/week over a period of approximately 4 hours per infusion for 27 weeks, and will eventually transition to 2.0 mg/kg/week for up to an additional 166 weeks.
| Study group | Role | What they receive |
|---|---|---|
| BMN 110 Weekly at 2.0 mg/kg/week | Experimental | Not described Receives: Drug: BMN 110 |
| BMN 110 Weekly at 4.0 mg/kg/week | Experimental | Not described Receives: Drug: BMN 110 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety Evaluation
The primary objective of the study is to evaluate the safety of weekly infusions of BMN 110; the safety variables included Adverse Events (AEs).
The primary outcome measure data is presented in more detail under the Adverse Events section.
Measured: Entire Study Period, up to 192 weeks or ETV (early termination visit)
Secondary outcomes (12)
6-minute Walk Test (6MWT)
Change from baseline to Week 12, 24, and 52 as measured in distance walked (meters) in 6MWT.
Measured: Baseline, Week 12, 24, and 52
3-minute Stair Climb Test (3MSCT)
Change from baseline to Week 12, 24, and 52 as measured in speed (stairs/min) in 3MSCT.
Measured: Baseline, Week 12, 24, and 52
Respiratory Function Test (MVV and FVC)
Respiratory Function was assessed by spirometry in accordance with American Thoracic Society standards.
Percent change from baseline to Week 12, 24, and 52 as measured by Maximum Voluntary Ventilation (MVV, L/min) Percent change from baseline to Week 12, 24, and 52 as measured by Forced Vital Capacity (FVC, L)
Measured: Baseline, Week 12, 24, and 52
Normalized Urine Keratan Sulfate (uKS)
Urinary KS was measured by a quantitative method and normalized using the sample urinary creatinine measurement.
Percent change from baseline to Week 12, 24, and 52 in normalized urine keratan sulfate (ug/mg).
Measured: Baseline, Week 12, 24, and 52
Cardiopulmonary Exercise Testing (CPET) - Duration of Exercise
Subjects performed maximal incremental exercise testing using an electronically braked upright cycle ergometer. Cycle ergometry is a method of CPET that may be feasible in subjects who have orthopedic, peripheral vascular, or neurological limitations that restrict weight bearing.
Change from baseline to Week 25 and 52 as measured by the CPET Duration of Exercise (min)
Measured: Baseline, Week 25 and 52
Cardiopulmonary Exercise Testing (CPET) - Peak Workload
Subjects performed maximal incremental exercise testing using an electronically braked upright cycle ergometer. Cycle ergometry is a method of CPET that may be feasible in subjects who have orthopedic, peripheral vascular, or neurological limitations that restrict weight bearing.
Percent change from baseline to Week 25 and 52 as measured by the CPET Peak workload (watt)
Measured: Baseline, Week 25 and 52
Cardiopulmonary Exercise Testing (CPET) - O2 Pulse
Subjects performed maximal incremental exercise testing using an electronically braked upright cycle ergometer. Cycle ergometry is a method of CPET that may be feasible in subjects who have orthopedic, peripheral vascular, or neurological limitations that restrict weight bearing.
Percent change from baseline to Week 25 and 52 as measured by the CPET O2 pulse (ml/beat)
Measured: Baseline, Week 25 and 52
Cardiopulmonary Exercise Testing (CPET) - Aerobic Efficiency
Subjects performed maximal incremental exercise testing using an electronically braked upright cycle ergometer. Cycle ergometry is a method of CPET that may be feasible in subjects who have orthopedic, peripheral vascular, or neurological limitations that restrict weight bearing.
Percent change from baseline to Week 25 and 52 as measured by the CPET Aerobic Efficiency (ml/watt).
Note that decline in Aerobic Efficiency translate into an improvement
Measured: Baseline, Week 25 and 52
Muscle Strength Testing (MST) - Knee Extension Test
Change from baseline to Week 25 and 52 as measured by the peak force in MST knee extension test (newton meters).
Measured: Baseline, Week 25 and 52
Muscle Strength Testing (MST) - Knee Flexion Test
Percent change from baseline to Week 25 and 52 as measured by the peak force in MST knee flexion test (newton meters).
Measured: Baseline, Week 25 and 52
Muscle Strength Testing (MST) - Elbow Flexion Test
Percent change from baseline to Week 25 and 52 as measured by the peak force in MST elbow flexion test (newton meters).
Measured: Baseline, Week 25 and 52
Adolescent Pediatric Pain Tool (APPT) - Pain Intensity
The APPT is a validated, multidimensional tool to evaluate pain in children, adolescents, and young adults. The complete APPT is measured in three parts - Part 1 of the APPT scale determines the subject's pain locations using a body template. Part 2 of the APPT scale determines the intensity of the pain using a 10 cm visual analog scale (VAS) with the lowest point of the scale (0) labeled No Pain and the highest point on the scale (10) labeled Worst Possible Pain. Intermediate regions of the sale were labeled with 3 intermediate descriptors (Little Pain, Medium Pain, and Large Pain). Part 3 of the APPT scale characterizes the pain by tracking the number and percentage of words selected by subjects to describe their pain from a total of 57 choices. Part 2 corresponds most closely to other typically used pain scales (based on VAS) and for this reason the results from Part 2 are presented here.
Change from baseline to Week 12, 24, and 52 in pain intensity.
Measured: Baseline, Week 12, 24, and 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2012 (estimated)
- Study startApr 2012
- Primary completionNov 2014
- Study completionNov 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.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioMarin Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Adam Shaywitz, MD PhD, Study director, BioMarin Pharmaceutical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01609062
- Sponsor's protocol ID
- MOR-008
- Status last verified
- Dec 2015
- First submitted
- 24 May 2012
- Last updated
- 1 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Berger KI, Burton BK, Lewis GD, Tarnopolsky M, Harmatz PR, Mitchell JJ, Muschol N, Jones SA, Sutton VR, Pastores GM, Lau H, Sparkes R, Shaywitz AJ. Cardiopulmonary Exercise Testing Reflects Improved Exercise Capacity in Response to Treatment in Morquio A Patients: Results of a 52-Week Pilot Study of Two Different Doses of Elosulfase Alfa. JIMD Rep. 2018;42:9-17. doi: 10.1007/8904_2017_70. Epub 2017 Nov 21.
PubMed 29159458
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Pilot Study of the Safety and Physiological Effects of Two Doses of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
- ClinicalTrials.gov ID
- NCT01609062
- Acronym / sponsor ID
- MOR-008
- 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
- 25 participants (actual)
- Lead sponsor
- BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- Apr 2012
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 31 May 2012 (estimated)
- Results
- Posted 1 Feb 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 was to evaluate the safety of a 2.0 mg/kg/week and a 4.0 mg/kg/week of BMN 110 in patients with Morquio A syndrome for up to 196 weeks. Secondary objectives were to investigate the effect of the two doses on exercise capacity for up to 196 weeks. In addition, the pharmacokinetic (PK) parameters of both doses of BMN 110 was assessed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BMN 110 Weekly at 2.0 mg/kg/week | Experimental | Drug: BMN 110 |
| BMN 110 Weekly at 4.0 mg/kg/week | Experimental | Drug: BMN 110 |
Who may qualify
- Ages
- 7 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Is willing and able to provide written, signed informed consent (or patient's legally authorized representative) after the nature of the study has been explained and prior to performance of any research- related procedure. Also, patients who do not meet country and local age requirements for informed consent must be willing and able to 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 performance of any research-related procedure.
- Has documented clinical diagnosis of Morquio A Syndrome (MPS IVA) based on clinical signs and symptoms of MPS IVA and documented reduced fibroblast or leukocyte N-acetylgalactosamine-6-sulfatase (GALNS) enzyme activity or genetic testing confirming diagnosis of MPS IVA.
- Is at least 7 years of age
- Is able to walk ≥ 200 meters as assessed by the 6-minute Walk Test (6MWT)
- If sexually active, is willing to use an acceptable method of contraception while participating in the study
Key exclusion criteria (17 listed)
- Inability to perform an exercise test due to limited mobility
- Body weight greater than 95 kg at Screening
- Severe, untreated sleep apnea as measured during Screening with a home sleep testing device
- Patients with a history of, or current condition of sleep apnea or sleep disordered breathing under adequate treatment may be enrolled if approved by the medical monitor.
- Requirement for supplemental oxygen
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-sulfataseWeekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for up to 192 weeks. | Drug | BMN 110 Weekly at 2.0 mg/kg/week |
| BMN 110Also: N-acetylgalactosamine-6-sulfatase, N-acetylgalactosamine-6-sulfate, sulfatase, galactose-6-sulfataseWeekly IV infusions of BMN 110 at 4.0 mg/kg/week over a period of approximately 4 hours per infusion for 27 weeks, and will eventually transition to 2.0 mg/kg/week for up to an additional 166 weeks. | Drug | BMN 110 Weekly at 4.0 mg/kg/week |
Primary outcome
Safety Evaluation
Time frame: Entire Study Period, up to 192 weeks or ETV (early termination visit)
The primary objective of the study is to evaluate the safety of weekly infusions of BMN 110; the safety variables included Adverse Events (AEs). The primary outcome measure data is presented in more detail under the Adverse Events section.
12 secondary outcomes
6-minute Walk Test (6MWT)
Time frame: Baseline, Week 12, 24, and 52
3-minute Stair Climb Test (3MSCT)
Time frame: Baseline, Week 12, 24, and 52
Respiratory Function Test (MVV and FVC)
Time frame: Baseline, Week 12, 24, and 52
Normalized Urine Keratan Sulfate (uKS)
Time frame: Baseline, Week 12, 24, and 52
Cardiopulmonary Exercise Testing (CPET) - Duration of Exercise
Time frame: Baseline, Week 25 and 52
Cardiopulmonary Exercise Testing (CPET) - Peak Workload
Time frame: Baseline, Week 25 and 52
Cardiopulmonary Exercise Testing (CPET) - O2 Pulse
Time frame: Baseline, Week 25 and 52
Cardiopulmonary Exercise Testing (CPET) - Aerobic Efficiency
Time frame: Baseline, Week 25 and 52
Muscle Strength Testing (MST) - Knee Extension Test
Time frame: Baseline, Week 25 and 52
Muscle Strength Testing (MST) - Knee Flexion Test
Time frame: Baseline, Week 25 and 52
Muscle Strength Testing (MST) - Elbow Flexion Test
Time frame: Baseline, Week 25 and 52
Adolescent Pediatric Pain Tool (APPT) - Pain Intensity
Time frame: Baseline, Week 12, 24, and 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29159458Berger KI, Burton BK, Lewis GD, Tarnopolsky M, Harmatz PR, Mitchell JJ, Muschol N, Jones SA, Sutton VR, Pastores GM, Lau H, Sparkes R, Shaywitz AJ. Cardiopulmonary Exercise Testing Reflects Improved Exercise Capacity in Response to Treatment in Morquio A Patients: Results of a 52-Week Pilot Study of Two Different Doses of Elosulfase Alfa. JIMD Rep. 2018;42:9-17. doi: 10.1007/8904_2017_70. Epub 2017 Nov 21.
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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.
Adam Shaywitz, MD PhD study director
BioMarin Pharmaceutical
11 sites in 4 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 11 sites in 4 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 7 inclusion and 17 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 1 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Canada, United Kingdom, 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 1 Feb 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?
Safety Evaluation (time frame: Entire Study Period, up to 192 weeks or ETV (early termination visit)). 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 NCT01609062, 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 1 Feb 2016.