Clinical Trial: BMN 110 Phase 3B in Australian Patients

Study Status: Enrolling by invitation
Recruit Status: Unknown status
Study Type: Interventional

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)

Brief Summary:

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


Detailed Summary:

STUDY DESIGN AND PLAN: This is a multicenter, open-label Phase 3B study designed to evaluate the safety and efficacy of BMN 110 in Australian patients with MPS IVA. Approximately 10 patients in Australia with a confirmed diagnosis of MPS IVA will be enrolled in this study. Eligible patients will receive weekly infusion of BMN 110 2.0 mg/kg until BMN 110 becomes commercially available in Australia.

Screening [Week -4]. After obtaining informed consent, information on demographics, concomitant medication(s) use and medical history (including pre-study growth data) will be collected; blood will be drawn for confirming MPS IVA diagnosis by enzymatic test (when applicable); and, blood and urine for clinical laboratory tests will be collected. Electrocardiogram (ECG), routine physical examination including standard neurological examination, vital signs; and cervical spine (flexion-extension) imaging by either radiographs, or a Magnetic Resonance Imaging (MRI) or CT scan may be collected during Screening visit. Adverse Events (AEs)/Serious Adverse Events (SAEs) will also be monitored and collected.

Baseline Visit [Week 1, Day -1]. Upon confirmation of eligibility by confirmed diagnosis of MPS IVA by enzymatic test, negative pregnancy tests at Baseline (in women of childbearing age) and medical history, patients will be enrolled in the study and will complete following assessments: urine KS and urine creatinine, vital signs, routine physical examination including standard neurological examination, body weight (for verifying dose), clinical laboratory assessments, immunogenicity tests, ECG, 6MW test, 3MSC test and RFT will be performed and AEs/SAEs and concomitant medication use will be collected. In addition, anthropometric parameters (including height) will be measured, pain assessment test (Adolescent Pediatric Pain Tool [APPT],
Sponsor: BioMarin Pharmaceutical

Current Primary Outcome: 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. ]

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.



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Efficacy Analysis [ Time Frame: Baseline, Week 25, Week 49 or Early Termination Visit ]

    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 ]
    The efficacy assessments as mentioned in Efficacy Analysis 2 above are all recommended in the Extension Phase per the protocol amendment dated 17Mar 2014


Original Secondary Outcome:

Information By: BioMarin Pharmaceutical

Dates:
Date Received: September 10, 2013
Date Started: July 2013
Date Completion: December 2015
Last Updated: January 27, 2015
Last Verified: August 2014