Safety and Exercise Study of Two Doses of BMN 110 for Morquio A Syndrome

NCT01609062 | Terminated Phase 2 Results DMC

• 1 other identifier: MOR-008
• Study Type: interventional
• Target: 25
• Locations: 4 countries
• Sites: 11

Brief Summary

The primary objective of this study was to evaluate the safety of a 2.0 mg/kg/week and a 4.0 mg/kg/week of BMN 110 in patients with Morquio A syndrome for up to 196 weeks. Secondary objectives were to investigate the effect of the two doses on exercise capacity for up to 196 weeks. In addition, the pharmacokinetic (PK) parameters of both doses of BMN 110 was assessed.

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-008; CPET; MST; muscle strength test; physiological effect

Outcome Measures

Primary Outcomes (1)

• Safety Evaluation

  The primary objective of the study is to evaluate the safety of weekly infusions of BMN 110; the safety variables included Adverse Events (AEs). The primary outcome measure data is presented in more detail under the Adverse Events section.

  Entire Study Period, up to 192 weeks or ETV (early termination visit)

Secondary Outcomes (12)

• 6-minute Walk Test (6MWT)

  Baseline, Week 12, 24, and 52

• 3-minute Stair Climb Test (3MSCT)

  Baseline, Week 12, 24, and 52

• Respiratory Function Test (MVV and FVC)

  Baseline, Week 12, 24, and 52

• Normalized Urine Keratan Sulfate (uKS)

  Baseline, Week 12, 24, and 52

• Cardiopulmonary Exercise Testing (CPET) - Duration of Exercise

  Baseline, Week 25 and 52

Study Arms (2)

BMN 110 Weekly at 2.0 mg/kg/week

EXPERIMENTAL

Drug: BMN 110

BMN 110 Weekly at 4.0 mg/kg/week

EXPERIMENTAL

Drug: BMN 110

Interventions

BMN 110 DRUG

Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for up to 192 weeks.

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

BMN 110 Weekly at 2.0 mg/kg/week

Eligibility Criteria

• Age: 7 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 patient's legally authorized representative) after the nature of the study has been explained and prior to performance of any research- related procedure. Also, patients who do not meet country and local age requirements for informed consent must be willing and able to provide written assent (if required) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to performance of any research-related procedure.
• Has documented clinical diagnosis of Morquio A Syndrome (MPS IVA) based on clinical signs and symptoms of MPS IVA and documented reduced fibroblast or leukocyte N-acetylgalactosamine-6-sulfatase (GALNS) enzyme activity or genetic testing confirming diagnosis of MPS IVA.
• Is at least 7 years of age
• Is able to walk ≥ 200 meters as assessed by the 6-minute Walk Test (6MWT)
• If sexually active, is 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 the Screening Visit and be willing to have additional pregnancy tests during the study
• Is willing and able to perform all study procedures, including cardiopulmonary exercise testing (CPET)

You may not qualify if:

• Inability to perform an exercise test due to limited mobility
• Body weight greater than 95 kg at Screening
• Severe, untreated sleep apnea as measured during Screening with a home sleep testing device
• Patients with a history of, or current condition of sleep apnea or sleep disordered breathing under adequate treatment may be enrolled if approved by the medical monitor.
• Requirement for supplemental oxygen
• Use of ventilator assistance in the 3 months prior to study entry
• Use of positive airway pressure (continuous positive airway pressure, CPAP, or bilevel airway pressure) for treatment of sleep apnea or sleep disordered breathing is allowed if settings have been stable for at least 1 month prior to study entry, and is approved by the medical monitor.
• 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 previous hematopoietic stem cell transplant (HSCT)
• Has received previous treatment with BMN 110
• Has a known hypersensitivity to BMN 110 or its excipients
• Has had major surgery within 3 months prior to study entry or is planning to have a major surgery during the duration of the study
• Use of any other investigational product (IP) or investigational medical device within 30 days prior to the beginning of the Screening Period or requires any investigational agent prior to completion of all scheduled study assessments
• Is pregnant or breastfeeding during the Screening Period or planning to become pregnant (self or partner) at any time during the study
• Has a concurrent disease or condition that may interfere with study participation or safety, and/or ability to perform study procedures as determined by the Investigator

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (11)

Unknown Facility

Oakland, California, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

New York, New York, United States

Location

Unknown Facility

Houston, Texas, United States

Location

Unknown Facility

Calgary, Alberta, Canada

Location

Unknown Facility

Toronto, Ontario, Canada

Location

Unknown Facility

Montreal, Quebec, Canada

Location

Unknown Facility

Sherbrook, Quebec, Canada

Location

Unknown Facility

Hamburg, Germany

Location

Unknown Facility

Belfast, Northern Ireland, United Kingdom

Location

Unknown Facility

Manchester, United Kingdom

Location

Related Publications (1)

• Berger KI, Burton BK, Lewis GD, Tarnopolsky M, Harmatz PR, Mitchell JJ, Muschol N, Jones SA, Sutton VR, Pastores GM, Lau H, Sparkes R, Shaywitz AJ. Cardiopulmonary Exercise Testing Reflects Improved Exercise Capacity in Response to Treatment in Morquio A Patients: Results of a 52-Week Pilot Study of Two Different Doses of Elosulfase Alfa. JIMD Rep. 2018;42:9-17. doi: 10.1007/8904_2017_70. Epub 2017 Nov 21.

  PMID: 29159458 DERIVED

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

• Adam Shaywitz, MD PhD

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2012
• First Posted: May 31, 2012
• Study Start: April 1, 2012
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: February 1, 2016
• Results First Posted: February 1, 2016

Record last verified: 2015-12

Locations

CA (4); US (4); GB (2); DE (1)