Safety/Tolerability/Pharmacokinetic (PK)/Pharmacodynamics (PD) Study of BMN701 in Patients With Late-Onset Pompe Disease

A Phase 1/2 Open-label Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamic and Preliminary Efficacy of BMN 701 (GILT-tagged Recombinant Human GAA) in Patients With Late-onset Pompe Disease

A Phase 1/2, open-label, multicenter, multiple dose escalation study of BMN 701 administered by intravenous infusion every 2 weeks over a 24-week treatment period to patients with late-onset Pompe disease.

Study Overview

• Status: Completed
• Conditions: Pompe Disease
• Intervention / Treatment: Biological: BMN 701

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Adelaide, SA
    • Adelaide, Adelaide, SA, Australia, 5006
      • Royal Adelaide Hospital, SA Pathology
• France
  • Nice, France, 06202
    • Hôpital de I´Archet- Centre Hospitalier Universitaire Nice
  • Paris Cedex 13, France, 75651
    • Hopital Pitie-Salpetriere
• Germany
  • Rheinland-pfalz
    • Mainz, Rheinland-pfalz, Germany, 55131
      • Zentrum für Kinder- und Jugenmedizin
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Old Queen Elizabeth Hospital, Department of Medicine
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital
  • Salford, United Kingdom, M6 8HD
    • Salford Royal Hospital NHS Trust
• United States
  • California
    • La Jolla, California, United States, 92103-8765
      • Univ of California San Diego School of Medicine
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida College of Medicine
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Patient has been diagnosed with Pompe Disease prior to or during the screening period based on 2 GAA gene mutations and either: endogenous GAA activity <75% of the lower limit of the normal adult range reported by the testing laboratory, as assessed in cultured skin fibroblasts -or- endogenous GAA activity <75% of the lower limit of the normal adult range reported by the testing laboratory, as assessed by dried blood spot or whole blood assay;
• Patient is male or female and 13 years of age or older at the time of enrollment in the study;
• Sexually active patients must be willing to use an acceptable method of contraception while participating in the study and for at least 4 months following the last dose of BMN 701;
• If patient is female and not considered to be of childbearing potential, she is at least 2 years post-menopausal or had tubal ligation at least 1 year prior to screening, or who have had total hysterectomy;
• If patient is female and of childbearing potential, she has negative urine pregnancy tests during the Screening Period and at the Baseline visit and be willing to have additional pregnancy tests during the study;
• Patient has ≥30% predicted upright FVC and either <80% predicted upright FVC, or >10% reduction in supine FVC compared to upright FVC during the Screening Period;
• Patient is naïve to Enzyme Replacement Therapy (ERT) with rhGAA;
• Patient must be able to ambulate at least 40 meters (131.2 feet) on the 6MWT conducted at the Screening visit (use of assistive devices such as walker, cane, or crutches, is permitted); and
• If subject was female, she was not lactating

Exclusion criteria:

• Patient has a history of diabetes or other disease known to cause hypoglycemia and is currently receiving, or might anticipate receiving, hypoglycemic agents during the course of the study;
• Patient has been on any immunosuppressive medication other than glucocorticosteroids within 1 year prior to enrollment into this study;
• Patient requires invasive ventilatory assistance at the time of enrollment into the study;
• Patient has received any investigational medication within 30 days prior to the first dose of study drug or is scheduled to receive any investigational drug other than BMN 701 during the course of the study;
• Patient has previously been admitted to the study;
• Patient is breastfeeding at screening or planning to become pregnant (self or partner) at any time during the study;
• Patient has a medical condition or extenuating circumstance that, in the opinion of the Investigator, might compromise the patient's ability to comply with the protocol requirements or compromise the patient's well being or safety;
• Patient 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BMN 701; IV infusion	Biological: BMN 701; GILT-tagged recombinant human GAA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	Number of Participants with Adverse Events as a Measure of Safety and Tolerability	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Six Minutes Walk Test	Change from Baseline in Six Minutes Walk Test. The 6MWT measured the maximum distance the subject could walk on a flat, hard surface in a period of 6 minutes	Baseline up to 24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Percent Predicted Upright Forced Vital Capacity	Change from Baseline in Percent Predicted Upright Forced Vital Capacity. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.	Baseline up to 24 week
Change From Baseline in Percent Predicted Supine Forced Vital Capacity	Change from Baseline in Percent Predicted Supine Forced Vital Capacity. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.	Baseline up to 24 weeks
Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure	Change from Baseline in Percent Predicted Upright Maximum Expiratory Pressure. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.	Baseline up to 24 weeks
Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure	Change from Baseline in Percent Predicted Upright Maximum Inspiratory Pressure. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.	Baseline up to 24 weeks
Change From Baseline in Upright Maximum Ventilatory Volume	Change from Baseline in Upright Maximum Ventilatory Volume. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.	Baseline up to 24 weeks

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical
• Investigators: Study Director: Medical Monitor, BioMarin Pharmaceutical

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2011
• Primary Completion (Actual): March 6, 2013
• Study Completion (Actual): March 6, 2013

Study Registration Dates

• First Submitted: October 27, 2010
• First Submitted That Met QC Criteria: October 28, 2010
• First Posted (Estimate): October 29, 2010

Study Record Updates

• Last Update Posted (Actual): June 11, 2018
• Last Update Submitted That Met QC Criteria: May 8, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Lysosomal Storage Diseases, Nervous System; Glycogen Storage Disease; Glycogen Storage Disease Type II
• Other Study ID Numbers: POM-001; 2010-023561-22 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No