BMN 110 Phase 3B in Australian Patients (MOR-AUS)
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.
Extension Phase is included per amendment dated 10Mar 2014: To provide patients enrolled in the Initial Phase access to BMN 110 until commercial product becomes available in Australia and continue to assess long-term safety
|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)|
- 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.
- 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.
- Efficacy Analysis (recommended) [ Time Frame: by Week 24, Week 52 and Early Termination Visit during Extension Phase ] [ Designated as safety issue: No ]The efficacy assessments as mentioned in Efficacy Analysis 2 above are all recommended in the Extension Phase per the protocol amendment dated 17Mar 2014
|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)|
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
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01966029
|Australia, New South Wales|
|Children's Hospital at Westmead|
|Westmead, New South Wales, Australia, 2145|
|Royal Children's Hospital|
|Brisbane, Queensland, Australia, 4029|
|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|
|Pain and Anaesthesia Research Clinic, Royal Adelaide Hospital|
|Adelaide, Australia, 5OOO|
|Study Director:||Eric He, MD||BioMarin Pharmaceutical|