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

Pompe Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01230801
• Other study ID #: POM-001
• Secondary ID: 2010-023561-22
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 17, 2011
• Est. completion date: March 6, 2013

Study information

• Verified date: May 2018
• Source: BioMarin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: March 6, 2013
• Est. primary completion date: March 6, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glycogen Storage Disease Type II
• Pompe Disease

Intervention

Biological:
• BMN 701
GILT-tagged recombinant human GAA

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital, SA Pathology	Adelaide	Adelaide, SA
France	Hôpital de I´Archet- Centre Hospitalier Universitaire Nice	Nice
France	Hôpital Pitié-Salpêtrière	Paris Cedex 13
Germany	Zentrum für Kinder- und Jugenmedizin	Mainz	Rheinland-pfalz
United Kingdom	Old Queen Elizabeth Hospital, Department of Medicine	Birmingham
United Kingdom	Royal Free Hospital	London
United Kingdom	Salford Royal Hospital NHS Trust	Salford
United States	University of Florida College of Medicine	Gainesville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Univ of California San Diego School of Medicine	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Countries where clinical trial is conducted

United States,  Australia,  France,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	Number of Participants With Adverse Events	Number of Participants with Adverse Events as a Measure of Safety and Tolerability	24 weeks
Secondary	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