Safety and Exercise Study of BMN 110 for Morquio A Syndrome

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT01609062
First received: May 24, 2012
Last updated: January 26, 2015
Last verified: January 2015
  Purpose

The primary objective of this study is 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 192 weeks. Secondary objectives will investigate the effect of the two doses on exercise capacity for up to 192 weeks. In addition, the pharmacokinetic (PK) parameters of both doses of BMN 110 will be assessed.


Condition Intervention Phase
Mucopolysaccharidosis IVA
Morquio A Syndrome
MPS IVA
Drug: BMN 110
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by BioMarin Pharmaceutical:

Primary Outcome Measures:
  • Descriptive summary of clinical safety assessments [ Time Frame: Continuously for up to 192 weeks/ETV ] [ Designated as safety issue: Yes ]

    Safety will be deteremined by the following factors:

    AEs, including SAEs, changes in physical examinations including neurological exams, vital signs, ECGs, Immunogenicity tests, standard clinical laboratory tests, and concomitant medications.



Secondary Outcome Measures:
  • Change in endurance using a summarized analysis of the percentage change in 6 Minute Walk Test (6MWT) and 3 Minute Stair Climb (3MSC) values from the Screening visit. [ Time Frame: Up to 192 weeks/ETV ] [ Designated as safety issue: No ]
    Timepoints: Screening Visit, Week 12, 24, 52, 96, 144, and 192/ETV

  • Change in absolute peak oxygen uptake from the Screening visit using cardio pulmonary exercise testing (CPET) to evaluate the effect on overall exercise capacity. [ Time Frame: Up to 29 weeks or more for Cohort A only ] [ Designated as safety issue: No ]

    All Cohort A will perform maximal exercise testing using an electronically braked up-right cycle ergometer. Expired oxygen and CO2 will be analyzed via an expired gas analysis system, heart rate will be monitored by continuous 3-lead ECG, and oxygen saturation will be measured bia pulse oximetry. A computer will be used to calculate breath by breath minute ventilation, oxygen uptake, CO@ production and respiratory exchange ratio (RER) from conventional equations.

    Timepoints: Screening and Week 25/ETV for Cohort A


  • Change in respiratory function using a summarized analysis of the percentage change in Spirometry, MVV, DLCO, and TLC values from the Screening visit. [ Time Frame: Up to 192 weeks/ETV ] [ Designated as safety issue: No ]
    Timepoints: Screening, Week 12, 24, 52, 96, 144, and 192/ETV

  • Correlation of the effect on muscle strength between Screening and Week 25 using an isokinetic dynamometer. [ Time Frame: Up to 29 weeks or more ] [ Designated as safety issue: No ]
    Timepoints: Screening and Week 25/ETV

  • Change in cardiac function as characterized by an Echocardiogram compared at Screening and Week 24 [ Time Frame: Up to week 192 ] [ Designated as safety issue: No ]
    Timepoints: Screening, week 24, 52, 96, 144, 192/ETV

  • Change in pain as determined by the Adolescent Pediatric Pain Tool, compared and correlated to the Screening Visit. [ Time Frame: Up to 29 weeks or more ] [ Designated as safety issue: No ]
    Timepoints: Screening, Week 12, and Week 24/ETV

  • Noncompartmental analysis of the area under the plasma concentration curve and the maximum observed plasma concentration of the pharmacokinetics for BMN 110 at 2.0 mg/kg/week and 4.0 mg/kg/week, over time. [ Time Frame: Up to 29 weeks or more ] [ Designated as safety issue: No ]
    Timepoints: Week 0 and Week 23

  • Change in plasma and urinary KS over time as determine by descriptive statistics. [ Time Frame: Up to 29 weeks (plasma KS)/ETV, or up to 192 weeks (urine KS)/ETV ] [ Designated as safety issue: No ]
    Timepoints: Plasma and Urine KS: Screening, Week 1, Week 2, Week 4, Week 6, Week 12, and Week 24/ETV; Urine KS: Week 52, Week 96, Week 120, Week 144, Week 168 and Week 192/ETV


Enrollment: 25
Study Start Date: April 2012
Study Completion Date: November 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BMN 110 Weekly at 2.0 mg/kg/week Drug: BMN 110
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.
Other Names:
  • N-acetylgalactosamine-6-sulfatase
  • N-acetylgalactosamine-6-sulfate
  • sulfatase
  • galactose-6-sulfatase
  • GALNS
  • enzyme replacement therapy
  • ERT
Experimental: BMN 110 Weekly at 4.0 mg/kg/week Drug: BMN 110
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.
Other Names:
  • N-acetylgalactosamine-6-sulfatase
  • N-acetylgalactosamine-6-sulfate
  • sulfatase
  • galactose-6-sulfatase
  • GALNS
  • enzyme replacement therapy
  • ERT

  Eligibility

Ages Eligible for Study:   7 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 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 at least 7 years of age
  • Is able to walk ≥ 200 meters as assessed by the 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 CPET

Exclusion Criteria:

  • 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
  • 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 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01609062

Locations
United States, California
Oakland, California, United States
United States, Illinois
Chicago, Illinois, United States
United States, New York
New York, New York, United States
United States, Texas
Houston, Texas, United States
Canada, Alberta
Calgary, Alberta, Canada
Canada, Ontario
Toronto, Ontario, Canada
Canada, Quebec
Montreal, Quebec, Canada
Sherbrook, Quebec, Canada
Germany
Hamburg, Germany
United Kingdom
Belfast, Northern Ireland, United Kingdom
Manchester, United Kingdom
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
Study Director: Adam Shaywitz, MD PhD BioMarin Pharmaceutical
  More Information

No publications provided

Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT01609062     History of Changes
Other Study ID Numbers: MOR-008
Study First Received: May 24, 2012
Last Updated: January 26, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Institute for Health Research
United Kingdom: Research Ethics Committee
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Canada: Health Canada

Keywords provided by BioMarin Pharmaceutical:
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

Additional relevant MeSH terms:
Mucopolysaccharidoses
Mucopolysaccharidosis IV
Syndrome
Carbohydrate Metabolism, Inborn Errors
Connective Tissue Diseases
Disease
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Mucinoses
Pathologic Processes

ClinicalTrials.gov processed this record on June 30, 2015