Efficacy and Safety Study of BMN 110 for Morquio A Syndrome Patients Who Have Limited Ambulation

NCT01697319 | Terminated Phase 2 Results DMC

• 2 other identifiers: MOR-0062011-005703-33
• Study Type: interventional
• Target: 16
• Locations: 3 countries
• Sites: 7

Brief Summary

The primary objective of this study is to evaluate the effect of 2.0 mg/kg/week BMN 110 in a patient population that has limited ambulation, in a period of up to 144 weeks.

Conditions

Mucopolysaccharidosis IVA; Morquio A Syndrome; MPS IVA

Keywords

Mucopolysaccharidosis IVA Type A; MPS IVA Type A; Mucopolysaccharidosis IVA; MPS IVA; Morquio A Syndrome; Lysosomal Storage Disorder; LSD; N-acetylgalactosamine-6-sulfatase; N-acetylgalactosamine-6-sulfate; sulfatase; galactose-6-sulfatase; GALNS; enzyme replacement therapy; ERT; MOR-006; CPET; Limited ambulation; Grip/ Pinch

Outcome Measures

Primary Outcomes (3)

• Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT)

  FDT assesses the ability to use the hand in daily tasks. The test involves turning 16 wooden pegs over as quickly as possible on a hardwood pegboard with one hand requiring a three-jaw chuck prehension pattern between the fingers and thumb within a two-minute time limit. Hand function is evaluated by how fast a patient can turn over pegs in the given time limit, i.e. speed (number of pegs/minute).

  Up to 96 weeks

• Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT)

  A grip-strength dynamometer and a pinch meter were used to measure grip strength and pinch strength. The results report change from baseline in strength for dominant and non-dominant hand in a forearm and wrist supported position.

  Up to 96 weeks

• Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT)

  The timed 25-Foot Walk Test (25FWT) is an assessment of mobility and performance of leg function. The patient was instructed to walk a marked 25-foot course as quickly as possible in a time limit of 3 minutes and immediately walk back the same distance when reaching one end.The patient is allowed to use any ambulation method to move. The outcome measures the speed (feet / min) of moving.

  Up to 96 weeks

Secondary Outcomes (1)

• Percent Change From Baseline in Normalized Urine Keratan Sulfate (uKS)

  Up to 96 weeks

Study Arms (1)

BMN 110 at 2.0 mg/kg/week

EXPERIMENTAL

Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for up to 144 weeks.

Drug: BMN 110

Interventions

BMN 110 DRUG

Drug will be delivered through a 4 hour (approximate) IV infusion at a dosage amount of 2.0 mg/kg/week for up to 144 weeks of treatment.

Also known as: N-acetylgalactosamine-6-sulfatase, N-acetylgalactosamine-6-sulfate, sulfatase, galactose-6-sulfatase, GALNS, enzyme replacement therapy, ERT, elosulfase alfa

BMN 110 at 2.0 mg/kg/week

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Is willing and able to provide written, signed informed consent (or their legally authorized representative) after the nature of the study has been explained and prior to performance of any research-related procedure. Patients who do not meet country and local age requirements for informed consent must be willing and able to provide written assent after the nature of the study has been explained and prior to performance of any research-related procedure.
• Has documented clinical diagnosis of MPS IVA based on clinical signs and symptoms of MPS IVA and documented reduced fibroblast or leukocyte GALNS enzyme activity or genetic testing confirming diagnosis of MPS IVA.
• Is ≥ 5 years of age.
• If sexually active, is willing to use an acceptable method of contraception while participating in the study.
• Females of childbearing potential must have a negative pregnancy test at the Screening Visit and be willing to have additional pregnancy tests during the study.
• Is willing and able to perform all study procedures as physically possible.

You may not qualify if:

• Is able to walk farther than a specified distance as assessed by the 6MWT.
• Has previous hematopoietic stem cell transplant (HSCT).
• Has received previous treatment with BMN 110.
• Has a known hypersensitivity to any of the components of BMN 110.
• Has had major surgery within 3 months prior to study entry or is planning to have a major surgery during the first 24 weeks of the study.
• Has used any other investigational product or investigational medical device within 30 days prior to the Screening Visit or requires any investigational agent prior to completion of all scheduled study assessments.
• Is pregnant or breastfeeding at the Screening Visit or planning to become pregnant (self or partner) at any time during the study.
• Has a concurrent disease or condition, including but not limited to symptomatic cervical spine instability or severe cardiac disease or complete paralysis due to a spinal cord injury (defined as an inability to move arms and legs), that would interfere with study participation or safety 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 (7)

Children's Hospital & Research Center Oakland

Oakland, California, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Location

Universitätsklinikum Hamburg

Hamburg, Germany

Location

University Medical Center Mainz, Center of Pediatric and Adolescent Medicine Villa Metabolica

Mainz, Germany

Location

NIHR/Wellcome Trust Birmingham CRF, Queen Elizabeth Hospital

Birmingham, United Kingdom

Location

Central Manchester University Hospitals NHS Foundation Trust

Manchester, United Kingdom

Location

Salford Royal NHS Foundation Trust

Salford, United Kingdom

Location

MeSH Terms

Conditions

Mucopolysaccharidosis IV; Lysosomal Storage Diseases

Interventions

GALNS protein, human; Chondroitinases and Chondroitin Lyases; Galns protein, mouse; Sulfatases; Enzyme Replacement Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Esterases; Hydrolases; Enzymes; Enzymes and Coenzymes; Polysaccharide-Lyases; Carbon-Oxygen Lyases; Lyases; Enzyme Therapy; Drug Therapy; Therapeutics

Results Point of Contact

• Title: BioMarin Medical Information Services
• Organization: BioMarin Pharmaceutical Inc.

medinfo@bmrn.com

800-983-4587

Study Officials

• Celeste Decker, M.D.

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2012
• First Posted: October 2, 2012
• Study Start: August 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: January 12, 2016
• Results First Posted: January 12, 2016

Record last verified: 2015-12

Locations

DE (2); GB (3); US (2)