BMN 110 Phase 3B in Australian Patients

NCT01966029 | Completed Phase 3 DMC

• 1 other identifier: 110-502
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 5

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

Conditions

Mucopolysaccharidosis IVA (Morquio A Syndrome)

Outcome Measures

Primary Outcomes (1)

• Safety Analysis

  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.

  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.

Secondary Outcomes (2)

• Efficacy Analysis

  Baseline, Week 25, Week 49 or Early Termination Visit

• Efficacy Analysis (recommended)

  by Week 24, Week 52 and Early Termination Visit during Extension Phase

Study Arms (1)

Treatment

EXPERIMENTAL

All patients receive treatment with BMN 110

Drug: BMN 110

Interventions

BMN 110 DRUG

All pateints receive treatment with BMN 110

Also known as: recombinant human N-acetylgalactosamine-6-sulfatase

Treatment

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Previous treatment with BMN 110.
• Has known hypersensitivity to any of the components of BMN 110.
• 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.

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (5)

Children's Hospital at Westmead

Westmead, New South Wales, 2145, Australia

Location

Lady Cilento Children's Hospital (previous: Royal Children's Hospital)

Brisbane, Queensland, 4101 (4029), Australia

Location

Murdoch Childrens Research Institute and Royal Children's Hospital

Melbourne, Victoria, 3052, Australia

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6008, Australia

Location

Pain and Anaesthesia Research Clinic, Royal Adelaide Hospital

Adelaide, 5OOO, Australia

Location

MeSH Terms

Conditions

Mucopolysaccharidosis IV

Interventions

GALNS protein, human; Chondroitinsulfatases

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Chondroitinases and Chondroitin Lyases; Sulfatases; Esterases; Hydrolases; Enzymes; Enzymes and Coenzymes

Study Officials

• Tristan Zhang, MD

  BioMarin Pharmaceutical

  STUDY DIRECTOR

• Eric He, MD

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2013
• First Posted: October 21, 2013
• Study Start: July 1, 2013
• Primary Completion: July 1, 2016
• Study Completion: December 1, 2016
• Last Updated: September 26, 2019

Record last verified: 2019-09

Locations

AU (5)