BMN 701 Phase 3 in rhGAA Exposed Subjects With Late Onset Pompe Disease (INSPIRE Study)

Late-onset Pompe Disease Clinical Trial

Official title:

A Phase 3 Switchover Study of the Efficacy and Safety of BMN 701 (GILT-tagged Recombinant Human GAA) and Long-Term Study for Extended Treatment in rhGAA Exposed Subjects With Late-onset Pompe Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01924845
• Other study ID #: 701-301
• Secondary ID: 2013-001768-48
• Status: Terminated
• Phase: Phase 3
• Start date: April 2014
• Est. completion date: September 12, 2016

Study information

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

Clinical Trial Summary

Study 701-301 is a single-arm, open-label, switchover study in patients with late-onset Pompe disease who have been receiving treatment with recombinant human acid alpha-glucosidase (rhGAA) for 48 weeks or longer. Ambulatory patients who have mild to moderate respiratory impairment will switch directly to receive BMN 701 20 mg/kg by IV infusion every other week. All participants will receive active drug. No dose of existing therapy will be missed - experimental drug is started immediately.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: September 12, 2016
• Est. primary completion date: September 12, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Willing and able to provide written informed consent, after the nature of the study has been explained, and prior to any study-related procedures.

• Diagnosed with late-onset Pompe disease based on 2 currently or previously documented GAA gene mutations, and 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.

• Has received prior treatment with commercial rhGAA as defined by ALL of the following:

1. has received treatment with commercial rhGAA for = 48 weeks (but no more than 20% of the study population can have received treatment for = 6 years).

2. has received > 80% of all scheduled treatments in the prior 48 weeks and = 4 out of the prior 6 scheduled treatments.

3. has received and completed the last two infusions without a drug-related adverse event resulting in dose interruption.

4. has received last treatment of commercial rhGAA = 10 and = 31 days prior to anticipated initiation of treatment with BMN 701.

• = 18 years of age at the time of enrollment in the study.

• Sexually active subjects must be willing to use two known effective methods of contraception while participating in the study and for at least 4 months following the last dose of BMN 701.

• Females of childbearing potential must have a negative pregnancy test at Screening and Baseline visits and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to Screening, or who have had total hysterectomy.

• Has = 30% predicted upright FVC and < 80% predicted upright FVC.

• Has =60% predicted MIP.

• Is able to ambulate =75 meters and =500 meters on the 6MWT conducted during the Screening visit (use of assistive devices such as walker, cane, or crutches, is permitted with consistent use throughout the study).

• Is willing and able to comply with all study procedures.

Exclusion Criteria:

• Use of any investigational product or investigational medical device within 4 weeks prior to Screening, or requirement for any investigational agent other than BMN 701 prior to completion of at least the first 24 weeks of all scheduled study assessments.

• Received any investigational medication for Pompe disease within the prior 12 months.

• Has a diagnosis of diabetes and/or is currently being treated with or anticipated to require treatment with hypoglycemic agents during the course of the study.

• Has been treated with any immunosuppressive medication other than glucocorticosteroids within the prior 12 months.

• Requires noninvasive ventilatory support while awake and in the upright position.

• Has previously been enrolled to this study.

• Breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.

• Concurrent disease, medical condition, or extenuating circumstance that, in the opinion of the Investigator, might compromise subject safety, study treatment compliance and completion of the study, or the integrity of the data collected for the study.

• Has known hypersensitivity to BMN 701 or its excipients.

Related Conditions & MeSH terms

• Glycogen Storage Disease Type II
• Late-onset Pompe Disease

Intervention

Drug:
• BMN 701
BMN 701 20 mg/kg for intravenous administration over approximately 4 hours every 2 weeks over a 24-week Treatment Period (total of 13 doses), and every 2 weeks over a 240-week Extension Period (up to 120 additional doses).

Locations

Country	Name	City	State
Belgium	Antwerp University Hospital (UZA)	Edegem
France	Hôpital Raymond Poincaré	Garches
France	CHU de la Timone	Marseille
Germany	Villa Metabolica, ZKJM MC University Mainz	Mainz
Germany	Klinikum der Universität München	München
Germany	Universitätsklinikum Münster	Münster
Italy	Azienda Ospedaliera Universitaria Policlinico "G. Martino" - Messina	Messina	ME
Italy	Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta	Milano
Netherlands	Erasmus MC University Medical Center	Rotterdam
Portugal	Centro Hospitalar de Sao Joao, EPE	Porto
United Kingdom	University Hospital Birmingham	Birmingham
United Kingdom	National Hospital for Neurology and Neurosurgery	London
United Kingdom	Royal Free Hospital	London
United Kingdom	Salford Royal NHS Foundation Trust	Salford
United States	The Ohio State University - Wexner Medical Center	Columbus	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Florida	Gainesville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of California, Irvine	Orange	California
United States	Neuromuscular Research Centre	Phoenix	Arizona
United States	Washington University	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Italy,  Netherlands,  Portugal,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Predicted Maximum Inspiratory Pressure (MIP)	Pulmonary function test: Percent Predicted Maximum Inspiratory Pressure	Baseline, Week 24
Secondary	Percent Predicted Maximum Expiratory Pressure (MEP)	Pulmonary function test: Percent Predicted Maximum Expiratory Pressure	Baseline, Week 24
Secondary	6 Minute Walk Test (Meters)	Distance walked within 6 minutes	Baseline, Week 24
Secondary	Percent Predicted Upright Forced Vital Capacity (FVC)	Pulmonary function test: Percent Predicted Upright Forced Vital Capacity	Baseline, Week 24
Secondary	Number of Participants With Non-Serious AEs	Number of participants with non-serious Adverse Events. Data is taken at final time point of Week 24, compared to baseline. For full AE data, please see AE section.	Baseline through Week 24 +4 weeks follow-up