Ignite Creation Date:
2024-05-06 @ 2:04 AM
Last Modification Date:
2024-10-26 @ 11:13 AM
Study NCT ID:
NCT01966029
Status:
COMPLETED
Last Update Posted:
2019-09-26
First Post:
2013-09-10
Brief Title:
BMN 110 Phase 3B in Australian Patients
Sponsor:
BioMarin Pharmaceutical
Organization:
BioMarin Pharmaceutical
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2019-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MOR-AUS
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 20 mgkgweek 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 12 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
The objective of this Phase 3B open label study 110-502 will be to evaluate the safety and tolerability of 20 mgkgweek 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 12 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 Description:
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 20 mgkg until BMN 110 becomes commercially available in Australia
Screening Week -4 After obtaining informed consent information on demographics concomitant medications 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 AEsSerious 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 AEsSAEs 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 AEsSAEs All assessments will be performed prior to treatment except AEsSAEs 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 AEsSAEs 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
Efficacy Assessment Visits Weeks 25 and 49 The following data will be collected during weeks 25 and 49 clinical laboratory tests urine KS and creatinine levels immunogenicity test ECG 6MW test 3MSC test RFTs and anthropometric measurements The patients will also complete the APPT testand PedsQL or SF-36 questionnaire as appropriate Patients who have abnormal overnight pulse oximetry readings will be assessed for sleep apnea Immunogenicity lab tests are completed only in the event of an Infusion Associated Reaction
Additional Safety Assessment during Week 49 Visit In addition to the efficacy and safety assessments listed above cervical spine radiographs flexion-extension or MRI or CT scan will also be collected during the Week 49 visit
Extension Phase Required Safety and Recommended Efficacy Assessments Treatment Visits Patients will be treated weekly with BMN110 starting at week 49 following completion of all applicable efficacy assessments until BMN110 becomes commercially available in Australia Patients will have vital signs concomitant medications and AEsSAEs collected at every visit Additional blood samples for total IgE and drug specific IgE testing will be drawn and analyzed for patients who experience a severe IAR experience an IAR requiring cessation of infusion anaphylaxis or a serious hypersensitivity event
Safety Assessments Treatment Visits Every 4 weeks Body weight will be obtained every 4 weeks after the Day 1 visit to confirm dose volume Treatment Visits Every 24 weeks In addition to the assessments performed at weekly treatment visits the patients will undergo pregnancy test as appropriate
Efficacy Assessments Recommended every 24 weeks starting with Week 73 Routine physical examination including standard neurological examination clinical laboratory assessments urine KS and creatinine levels ECG 6MW test 3MSC test RFTs and anthropometric measurements The patients will also complete the APPT test and PedsQL or SF-36 questionnaire as appropriate cervical spine imaging and sleep apnea test if applicable Patients who have abnormal overnight pulse oximetry readings will be assessed for sleep apnea
End of Study Visit EOS The patients will be monitored for AEs and SAEs for up to 30 days post drug infusion During Week 53 the EOS Visit patients will be evaluated for AEsSAEs and will have vital signs taken routine physical examination including standard neurological examination will be performed and information on concomitant medication use will be collected
Patient withdrawal Patients may withdraw voluntarily from receiving BMN 110 at any time in which case they will be encouraged to continue to undergo study assessments Data from such patients will be utilized for further characterization of the natural progression of MPS IVA Patients may also withdraw entirely from study participation at any time
Safety 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 Starting on the first Screening Day and continuing through the end of the study or Early Termination Visit AEsSAEs will be monitored and recorded and routine physical examination including standard neurological examination will be conducted in all patients During the Initial Phase routine physical examination including standard neurological examination will be conducted in all patients During the Extension phase physical examinations including neurologic examinations are recommended but not required
Some patients may experience infusion associated reactions IARs associated with the administration of study drug thus it will be required that prophylactic antihistamine will be administered prior to each study drug infusion Antipyretic pretreatment may be given at the Investigators discretion The internal Data Monitoring Committee DMC will monitor the safety of BMN 110 in patients and may review any severe or serious IARs that occur in patients during the study until approval from the United States Food and Drug Administration or the European Medicines Agency to commercialize BMN 110 is received Vital signs will be measured just before during and immediately following the study drug infusion Adverse events and changes in concomitant medication Safety assessments will be performed throughout the study Physical examinations including neurological examination will be performed at Screening and all visits up to and including the Week 49 Visit
Radiographs flexion-extension or MRI or CT scans of the cervical spine are required at Screening and at Week 49 Clinical laboratory tests Electrocardiograms ECG are required at Screening Baseline Weeks 25 and 49 Visits Blood samples will be collected at Baseline Weeks 25 and 49 for TAb and NAb testing NAb will not be performed if TAb is negative Samples for Total IgE will be collected at Baseline and stored for testing For patients who experience a severe infusion associated reaction IAR experience an IAR requiring cessation of infusion anaphylaxis or a serious hypersensitivity event shortly after cessation of the infusion the Baseline total IgE sample will be analyzed and additional blood samples for total IgE and drug-specific IgE testing will be drawn and run Immediate testing for total IgE will be taken shortly after cessation of the study drug infusion Drug-specific IgE will also be tested but must be collected no sooner than 8 hours post infusion and no later than just before the next scheduled infusion the following week due to rhGALNS interference with the detection assay A sample taken the day after the IAR anaphylactic or serious hypersensitivity event would be preferred but may not be practical If the sample is positive the extra volume of serum may be used to further characterize the drug-specific IgE assay As patients may experience hypersensitivity reactions associated with the administration of BMN 110 all patients will be pretreated with an appropriate dose of antihistamine medication approximately 30 minutes to 1 hour prior to infusion Antipyretic medications may also be given at the discretion of the Investigator On infusion days vital signs will be measured at a minimum of immediately before less than 30 minutes the infusion every 30 minutes for the first hour of the infusion every hour for the remainder of the infusion and immediately less than 30 minutes after the infusion Patients will also be monitored by continuous pulse oximetry during infusion and for at least 60 minutes after the infusion is completed AEsSAEs and changes in concomitant medication will be recorded throughout the study AEsSAEs will be graded according to the National Cancer Institute NCI Common Terminology Criteria for Adverse Events CTCAE
Screening Week -4 After obtaining informed consent information on demographics concomitant medications 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 AEsSerious 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 AEsSAEs 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 AEsSAEs All assessments will be performed prior to treatment except AEsSAEs 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 AEsSAEs 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
Efficacy Assessment Visits Weeks 25 and 49 The following data will be collected during weeks 25 and 49 clinical laboratory tests urine KS and creatinine levels immunogenicity test ECG 6MW test 3MSC test RFTs and anthropometric measurements The patients will also complete the APPT testand PedsQL or SF-36 questionnaire as appropriate Patients who have abnormal overnight pulse oximetry readings will be assessed for sleep apnea Immunogenicity lab tests are completed only in the event of an Infusion Associated Reaction
Additional Safety Assessment during Week 49 Visit In addition to the efficacy and safety assessments listed above cervical spine radiographs flexion-extension or MRI or CT scan will also be collected during the Week 49 visit
Extension Phase Required Safety and Recommended Efficacy Assessments Treatment Visits Patients will be treated weekly with BMN110 starting at week 49 following completion of all applicable efficacy assessments until BMN110 becomes commercially available in Australia Patients will have vital signs concomitant medications and AEsSAEs collected at every visit Additional blood samples for total IgE and drug specific IgE testing will be drawn and analyzed for patients who experience a severe IAR experience an IAR requiring cessation of infusion anaphylaxis or a serious hypersensitivity event
Safety Assessments Treatment Visits Every 4 weeks Body weight will be obtained every 4 weeks after the Day 1 visit to confirm dose volume Treatment Visits Every 24 weeks In addition to the assessments performed at weekly treatment visits the patients will undergo pregnancy test as appropriate
Efficacy Assessments Recommended every 24 weeks starting with Week 73 Routine physical examination including standard neurological examination clinical laboratory assessments urine KS and creatinine levels ECG 6MW test 3MSC test RFTs and anthropometric measurements The patients will also complete the APPT test and PedsQL or SF-36 questionnaire as appropriate cervical spine imaging and sleep apnea test if applicable Patients who have abnormal overnight pulse oximetry readings will be assessed for sleep apnea
End of Study Visit EOS The patients will be monitored for AEs and SAEs for up to 30 days post drug infusion During Week 53 the EOS Visit patients will be evaluated for AEsSAEs and will have vital signs taken routine physical examination including standard neurological examination will be performed and information on concomitant medication use will be collected
Patient withdrawal Patients may withdraw voluntarily from receiving BMN 110 at any time in which case they will be encouraged to continue to undergo study assessments Data from such patients will be utilized for further characterization of the natural progression of MPS IVA Patients may also withdraw entirely from study participation at any time
Safety 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 Starting on the first Screening Day and continuing through the end of the study or Early Termination Visit AEsSAEs will be monitored and recorded and routine physical examination including standard neurological examination will be conducted in all patients During the Initial Phase routine physical examination including standard neurological examination will be conducted in all patients During the Extension phase physical examinations including neurologic examinations are recommended but not required
Some patients may experience infusion associated reactions IARs associated with the administration of study drug thus it will be required that prophylactic antihistamine will be administered prior to each study drug infusion Antipyretic pretreatment may be given at the Investigators discretion The internal Data Monitoring Committee DMC will monitor the safety of BMN 110 in patients and may review any severe or serious IARs that occur in patients during the study until approval from the United States Food and Drug Administration or the European Medicines Agency to commercialize BMN 110 is received Vital signs will be measured just before during and immediately following the study drug infusion Adverse events and changes in concomitant medication Safety assessments will be performed throughout the study Physical examinations including neurological examination will be performed at Screening and all visits up to and including the Week 49 Visit
Radiographs flexion-extension or MRI or CT scans of the cervical spine are required at Screening and at Week 49 Clinical laboratory tests Electrocardiograms ECG are required at Screening Baseline Weeks 25 and 49 Visits Blood samples will be collected at Baseline Weeks 25 and 49 for TAb and NAb testing NAb will not be performed if TAb is negative Samples for Total IgE will be collected at Baseline and stored for testing For patients who experience a severe infusion associated reaction IAR experience an IAR requiring cessation of infusion anaphylaxis or a serious hypersensitivity event shortly after cessation of the infusion the Baseline total IgE sample will be analyzed and additional blood samples for total IgE and drug-specific IgE testing will be drawn and run Immediate testing for total IgE will be taken shortly after cessation of the study drug infusion Drug-specific IgE will also be tested but must be collected no sooner than 8 hours post infusion and no later than just before the next scheduled infusion the following week due to rhGALNS interference with the detection assay A sample taken the day after the IAR anaphylactic or serious hypersensitivity event would be preferred but may not be practical If the sample is positive the extra volume of serum may be used to further characterize the drug-specific IgE assay As patients may experience hypersensitivity reactions associated with the administration of BMN 110 all patients will be pretreated with an appropriate dose of antihistamine medication approximately 30 minutes to 1 hour prior to infusion Antipyretic medications may also be given at the discretion of the Investigator On infusion days vital signs will be measured at a minimum of immediately before less than 30 minutes the infusion every 30 minutes for the first hour of the infusion every hour for the remainder of the infusion and immediately less than 30 minutes after the infusion Patients will also be monitored by continuous pulse oximetry during infusion and for at least 60 minutes after the infusion is completed AEsSAEs and changes in concomitant medication will be recorded throughout the study AEsSAEs will be graded according to the National Cancer Institute NCI Common Terminology Criteria for Adverse Events CTCAE
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None