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)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 5
- 主要终点
- Safety Analysis
研究概览
简要总结
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
详细描述
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], pain tool in children, adolescents, and adults) will be administered; and PedsQL (QOL questionnaire for pediatric patients) or SF-36 (QOL questionnaire for adult patients) questionnaire will also be completed during this visit. Patients who have abnormal overnight pulse oximetry readings will be assessed for sleep apnea, the results of which will be calculated using the Apnea-Hypopnea Index (AHI) at Baseline, Week 25, Week 49 and ETV.
Treatment Visit 1 [Week 1, Day 1]. Patients will receive the first dose of BMN 110 by intravenous (IV) infusion. Assessments on Day 1 will include vital signs, routine physical examination including standard neurological examination, and concomitant medication use and AEs/SAEs. All assessments will be performed prior to treatment, except AEs/SAEs which are collected continuously throughout the study. Immunogenicity lab tests are completed only in the event of an Infusion Associated Reaction.
Treatment Visits [Weeks 2-48]. Patients will be treated weekly with BMN 110 for 48 weeks. Prior to each weekly treatment, patients will have vital signs and routine physical examination including standard neurological examination. Concomitant medications and AEs/SAEs are collected at every visit. Body weight will be determined every 4 weeks after the Day -1 visit to confirm dose volume. Immunogenicity lab tests are completed only in the event of an Infusion Associated Reaction.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
- •Age 12 months or older.
- •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.
- •If sexually active, must be willing to use an acceptable method of contraception while participating in the study.
- •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.
排除标准
- •Previous treatment with BMN
- •Has known hypersensitivity to any of the components of BMN
- •Major surgery within 3 months prior to study entry or planned major surgery during the 48-week treatment period.
- •Prior bone marrow transplant (BMT) or hematopoietic stem cell transplant (HSCT).
- •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.
- •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.
- •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.
- •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.
研究组 & 干预措施
Treatment
All patients receive treatment with BMN 110
干预措施: BMN 110 (Drug)
结局指标
主要结局
Safety Analysis
时间窗: 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.
次要结局
- Efficacy Analysis (recommended)(by Week 24, Week 52 and Early Termination Visit during Extension Phase)
- Efficacy Analysis(Baseline, Week 25, Week 49 or Early Termination Visit)