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

• ClinicalTrials.gov Identifier: NCT01230801
• Recruitment Status: Completed
• First Posted: October 29, 2010
• Results First Posted: June 11, 2018
• Last Update Posted: June 11, 2018
• Sponsor: BioMarin Pharmaceutical
• Information provided by (Responsible Party): BioMarin Pharmaceutical

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pompe Disease	Biological: BMN 701	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 17, 2011
• Actual Primary Completion Date: March 6, 2013
• Actual Study Completion Date: March 6, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Adverse Events [ Time Frame: 24 weeks ]
   Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Secondary Outcome Measures :

1. Change From Baseline in Six Minutes Walk Test [ Time Frame: Baseline up to 24 weeks ]
   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

Other Outcome Measures:

1. Change From Baseline in Percent Predicted Upright Forced Vital Capacity [ Time Frame: Baseline up to 24 week ]
   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.
2. Change From Baseline in Percent Predicted Supine Forced Vital Capacity [ Time Frame: Baseline up to 24 weeks ]
   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.
3. Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure [ Time Frame: Baseline up to 24 weeks ]
   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.
4. Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure [ Time Frame: Baseline up to 24 weeks ]
   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.
5. Change From Baseline in Upright Maximum Ventilatory Volume [ Time Frame: Baseline up to 24 weeks ]
   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, California

Univ of California San Diego School of Medicine

La Jolla, California, United States, 92103-8765

United States, Florida

University of Florida College of Medicine

Gainesville, Florida, United States, 32610

United States, Kansas

University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

Australia, Adelaide, SA

Royal Adelaide Hospital, SA Pathology

Adelaide, Adelaide, SA, Australia, 5006

France

Hôpital de I´Archet- Centre Hospitalier Universitaire Nice

Nice, France, 06202

Hôpital Pitié-Salpêtrière

Paris Cedex 13, France, 75651

Germany

Zentrum für Kinder- und Jugenmedizin

Mainz, Rheinland-pfalz, Germany, 55131

United Kingdom

Old Queen Elizabeth Hospital, Department of Medicine

Birmingham, United Kingdom, B15 2TH

Royal Free Hospital

London, United Kingdom, NW3 2QG

Salford Royal Hospital NHS Trust

Salford, United Kingdom, M6 8HD

Sponsors and Collaborators

BioMarin Pharmaceutical

Investigators

• Study Director: Medical Monitor; BioMarin Pharmaceutical

More Information

• Responsible Party: BioMarin Pharmaceutical
• ClinicalTrials.gov Identifier: NCT01230801
• Other Study ID Numbers: POM-001; 2010-023561-22 ( EudraCT Number )
• First Posted: October 29, 2010
• Results First Posted: June 11, 2018
• Last Update Posted: June 11, 2018
• Last Verified: May 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Glycogen Storage Disease Type II; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases