A Phase 3 Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 110 in Patients with Mucopolysaccharidosis IVA (Morquio A Syndrome)

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2010-020199-45-GB
• Date of registration: 06/05/2011
• Prospective Registration: Yes
• Primary sponsor: BioMarin Pharmaceutical Inc.
• Public title: A Phase 3 Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 110 in Patients with Mucopolysaccharidosis IVA (Morquio A Syndrome)
• Scientific title: A Multicenter, Multinational, Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 110 in Patients with Mucopolysaccharidosis IVA (Morquio A Syndrome)
• Date of first enrolment: 08/06/2011
• Target sample size: 162
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020199-45
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Brazil, Canada, Colombia, Denmark, France, Germany, Italy, Japan, Korea, Republic of, Netherlands, Norway, Poland, Portugal, Qatar, Saudi Arabia, Spain, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Trials Information
• Affiliation: BioMarin Pharmaceutical Inc.

• Name: Clinical Trials Information
• Affiliation: BioMarin Pharmaceutical Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
• Must have completed MOR-004.
• Is 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, of childbearing potential, must have a negative pregnancy test at Baseline and be willing to have additional pregnancy tests done during the study.
Are the trial subjects under 18? yes
Number of subjects for this age range: 110
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Is pregnant or breastfeeding, at Baseline, or planning to become pregnant (self or partner) at any time during the study.
• Has used any investigational product (other than BMN 110 in MOR-004), 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.
• Was enrolled in a previous BMN 110 study, other than MOR-004.
• Has a concurrent disease or condition, including but not limited to, symptomatic cervical spine instability, clinically significant 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Mucopolysaccharidosis Type IVA
MedDRA version: 14.1 Level: PT Classification code 10028095 Term: Mucopolysaccharidosis IV System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Product Name: recombinant human N-acetylgalactosamine-6-sulfatase (rhGALNS)
Product Code: BMN 110
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not Available
CAS Number: 9025-60-9
Current Sponsor code: rhGALNS
Other descriptive name: recombinant human N-acetylgalactosamine-6-sulfatase, BMN 110 drug substance
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: To evaluate the long-term effect of BMN 110 administration at 2.0 mg/kg/qw and 2.0 mg/kg/qow on changes in biochemical markers of inflammation and bone and cartilage metabolism, in patients with MPS IVA.

Primary end point(s): Efficacy Variables:
• endurance tests:
- 6 minute walk (6MW) test
- 3 minute stair climb (3MSC) test
• urine KS concentration (normalized to creatinine)
• respiratory function tests:
- forced expiratory time (FET)
- forced expiratory volume in 1 second (FEV1)
- forced inspiratory vital capacity (FIVC)
- forced vital capacity (FVC)
- maximum voluntary ventilation (MVV)
• anthropometric measurements (standing height, length, sitting height, and weight)
• skeletal X-rays of lumbar spine and lower extremity
• MPS Health Assessment Questionnaire
• audiometry examinations
Safety Variables:
• adverse events (AEs)
• standard clinical laboratory tests (serum chemistry, hematology, and urinalysis)
• vital signs
• echocardiograms
• electrocardiograms (ECGs)
• routine physical examinations (including standard neurologic examination)
• concomitant medications
• immunogenicity tests
• cervical spine (flexion–extension) X-rays

Timepoint(s) of evaluation of this end point: • 6MW test, 3MSC test: baseline, wk 12, every 24 wks in Part 1, every 48 wks in Part 2
• respiratory function tests: baseline, every 24 wks in Part 1, every 48 wks in Part 2
• anthropometric measurements, MPS Health Assessment Questionnaire, audiometry examinations: baseline, every 24 wks in Part 1 and Part 2
• adverse events, vital signs, concomitant medications: baseline, weekly in Part 1, weekly or every other week in Part 2
• echocardiograms, electrocardiograms: baseline, every 48 wks in Part 2
• routine physical examinations, immunogenicity tests, standard clinical laboratory tests, urine KS concentration: baseline, every 12 wks in Part 1, every 24 wks in Part 2
• x-rays of cervical spine, lumbar spine and lower extremity: baseline, every 72 wks in Part 2

Main Objective: To evaluate the long-term safety and efficacy of BMN 110 administration at 2.0 mg/kg/qw and 2.0 mg/kg/qow in patients with MPS IVA.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Exploratory Variables:
• blood inflammatory biomarkers, and blood biochemical markers of bone and cartilage metabolism: baseline, every 24 wks in Part 1 and Part 2
•To evaluate patient perception of impairment and improvement in patients with MPS IVA.

Secondary end point(s): Exploratory Variables:
• blood inflammatory biomarkers
• blood biochemical markers of bone and cartilage metabolism

Secondary ID(s)

NCT01415427

MOR-005

Source(s) of Monetary Support

BioMarin Pharmaceutical Inc.

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 06/07/2018
• Date Completed: 16/06/2016
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-020199-45/results