BMN 110 Phase 3B in Australian Patients (MOR-AUS)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT01966029
First received: September 10, 2013
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

There is currently no treatment for MPS IVA other than supportive care for the clinical manifestations of the disease. Enzyme replacement therapy (ERT) with BMN 110 to replace the deficient GALNS is a potential new treatment option for MPS IVA patients. BMN 110,containing recombinant human GALNS (rhGALNS) developed by BioMarin is expected to reduce the progressive, pathologic accumulation of KS, and improve signs and symptoms of the disease.

The objective of this Phase 3B open label study (110-502) will be to evaluate the safety and tolerability of 2.0 mg/kg/week (qw) of BMN 110 in Australian patients with MPS IVA. In addition, a number of secondary and tertiary efficacy endpoints will also be investigated. The dose and regimen of BMN 110 have been selected on the basis of data from a Phase 1/2 clinical study with BMN 110, nonclinical and in vitro studies with BMN 110, and clinical and nonclinical data from other enzyme replacement therapies.


Condition Intervention Phase
Mucopolysaccharidosis IVA (Morquio A Syndrome)
Drug: BMN 110
Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter Open-Label, Phase 3B Study to Evaluate the Efficacy and Safety of BMN 110 in Australian Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)

Resource links provided by NLM:


Further study details as provided by BioMarin Pharmaceutical:

Primary Outcome Measures:
  • Safety Analysis [ Time Frame: The study period during which all non-serious AEs and SAEs will be reported begins after informed consent is obtained and through 30 days after the last study visit or 30 days after the last drug infusion, whichever comes first. ] [ Designated as safety issue: Yes ]

    The analyses of safety will include all patients who receive any study drug. All safety data will be summarized descriptively. All AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). The incidence of AEs will be summarized by System Organ Class (SOC), Preferred Term (PT), relationship to study drug, and severity. Patient listings will be provided for SAEs, deaths, and AEs leading to study drug discontinuation, or study withdrawals. All AE summaries will include only treatment-emergent AEs (TEAEs) reported during the study period (AEs that occur after the first study drug infusion). Infusion-associated AEs will be summarized by SOC, PT and severity.

    The following safety measures will be summarized descriptively: concomitant medications, clinical laboratory tests, vital signs, ECGs, immunogenicity results, analgesic medication use, results from routine physical examinations (including standard neurologic examinations), and cervical spine imaging.



Secondary Outcome Measures:
  • Efficacy Analysis [ Time Frame: Baseline, Week 25, Week 49 or Early Termination Visit ] [ Designated as safety issue: No ]

    Efficacy assessments and procedures are the duplicate endurance testing (6MW and 3MSC tests) at Baseline and at week 25 and 49. Samples for urine KS and urine creatinine will be collected at Baseline and every 24 weeks.

    Anthropometric measurements, including standing height, length, sitting height, knee height (as clinically indicated), head circumference and weight, will be taken at Baseline and every 24 weeks.

    Respiratory function tests (RFTs) for assessment of forced expiratory volume for 1 second (FEV1), forced inspiratory vital capacity (FIVC), forced vital capacity (FVC), and maximum voluntary ventilation (MVV) will be performed at Baseline and Weeks 25 and 49. APPT (pain assessment tool), and the PedsQL (Pediatric Quality of Life Inventory) or SF-36® (QOL questionnaire for adult patients) will be done at Baseline, Week 25, and Week 49. The Sleep Apnea Test will be done at Baseline, Week 25 and Week 49, if applicable.



Estimated Enrollment: 14
Study Start Date: July 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
All patients receive treatment with BMN 110
Drug: BMN 110
All pateints receive treatment with BMN 110
Other Name: recombinant human N-acetylgalactosamine-6-sulfatase

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  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosed with MPS IVA as confirmed by a documented GALNS enzymatic test (GALNS activity in affected range, beta-galactosidase and a second lysosomal sulfatase activity within normal range).
  2. Age 12 months or older.
  3. 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 authorized representative, after the nature of the study has been explained, and prior to performance of research-related procedures.
  4. If sexually active, must be willing to use an acceptable method of contraception while participating in the study.
  5. If female, and of childbearing potential, must have a negative pregnancy test at Baseline and be willing to have additional pregnancy tests done during the study. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to Screening, or who have had total hysterectomy. Childbearing potential will be assessed by the investigator.

Exclusion Criteria:

  1. Previous treatment with BMN 110.
  2. Has known hypersensitivity to any of the components of BMN 110.
  3. Major surgery within 3 months prior to study entry or planned major surgery during the 48-week treatment period.
  4. Prior bone marrow transplant (BMT) or hematopoietic stem cell transplant (HSCT).
  5. Is pregnant or breastfeeding at Baseline, or planning to become pregnant (self orpartner) at any time during the study. Patients who become pregnant during the study will be discontinued from the study.
  6. Has used any investigational product, 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.
  7. Has a concurrent disease or condition, including but not limited to, symptomatic cervical spine instability, clinically significant and/or progressive spinal cord compression, or severe cardiac disease that would interfere with study participation, or pose a safety risk, as determined by the Investigator.
  8. 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: NCT01966029

Locations
Australia, New South Wales
Children's Hospital at Westmead
Westmead, New South Wales, Australia, 2145
Australia, Queensland
Royal Children's Hospital
Brisbane, Queensland, Australia, 4029
Australia, Victoria
Murdoch Childrens Research Institute and Royal Children's Hospital
Melbourne, Victoria, Australia, 3052
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6008
Australia
Pain and Anaesthesia Research Clinic, Royal Adelaide Hospital
Adelaide, Australia, 5OOO
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
Study Director: Eric He, MD BioMarin Pharmaceutical
  More Information

No publications provided

Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT01966029     History of Changes
Other Study ID Numbers: 110-502
Study First Received: September 10, 2013
Last Updated: August 11, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

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

ClinicalTrials.gov processed this record on August 21, 2014