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

NCT01924845 | Terminated Phase 3 Results DMC

• 2 other identifiers: 701-3012013-001768-48
• Study Type: interventional
• Target: 24
• Locations: 8 countries
• Sites: 22

Brief 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.

Conditions

Late-onset Pompe Disease

Outcome Measures

Primary Outcomes (1)

• Percent Predicted Maximum Inspiratory Pressure (MIP)

  Pulmonary function test: Percent Predicted Maximum Inspiratory Pressure

  Baseline, Week 24

Secondary Outcomes (4)

• Percent Predicted Maximum Expiratory Pressure (MEP)

  Baseline, Week 24

• 6 Minute Walk Test (Meters)

  Baseline, Week 24

• Percent Predicted Upright Forced Vital Capacity (FVC)

  Baseline, Week 24

• Number of Participants With Non-Serious AEs

  Baseline through Week 24 +4 weeks follow-up

Study Arms (1)

BMN 701 20 mg/kg

EXPERIMENTAL

BMN 701 IV Infusion 20mg/kg every 2 weeks for 24 weeks followed by an optional extension of 240 weeks (total duration of therapy 264 weeks)

Drug: BMN 701

Interventions

BMN 701 DRUG

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).

BMN 701 20 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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).
• has received \> 80% of all scheduled treatments in the prior 48 weeks and ≥ 4 out of the prior 6 scheduled treatments.
• has received and completed the last two infusions without a drug-related adverse event resulting in dose interruption.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (22)

Neuromuscular Research Centre

Phoenix, Arizona, 85028, United States

Location

University of California, Irvine

Orange, California, 92868, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Washington University

St Louis, Missouri, 36110, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Ohio State University - Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Antwerp University Hospital (UZA)

Edegem, Belgium

Location

Hôpital Raymond Poincaré

Garches, 92380, France

Location

CHU de la Timone

Marseille, 13005, France

Location

Villa Metabolica, ZKJM MC University Mainz

Mainz, Germany

Location

Klinikum der Universität München

München, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Azienda Ospedaliera Universitaria Policlinico "G. Martino" - Messina

Messina, ME, 98125, Italy

Location

Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

Milan, 20133, Italy

Location

Erasmus MC University Medical Center

Rotterdam, 3015 GJ, Netherlands

Location

Centro Hospitalar de Sao Joao, EPE

Porto, 4200-319, Portugal

Location

University Hospital Birmingham

Birmingham, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

National Hospital for Neurology and Neurosurgery

London, United Kingdom

Location

Salford Royal NHS Foundation Trust

Salford, M5 5AP, United Kingdom

Location

Limitations and Caveats

Complete efficacy analyses were not able to be completed due to early study termination; however, efficacy results from interim analysis at week 24 are available, and thus have been reported.

Results Point of Contact

• Title: Debra Lounsbury, Principal Scientist, Clinical Sciences
• Organization: BioMarin Pharmaceuticals

DLounsbury@bmrn.com

415-506-6348

Study Officials

• Study Monitor

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2013
• First Posted: August 19, 2013
• Study Start: April 1, 2014
• Primary Completion: September 12, 2016
• Study Completion: September 12, 2016
• Last Updated: June 14, 2018
• Results First Posted: June 14, 2018

Record last verified: 2018-06

Locations

PT (1); DE (3); US (8); NL (1); BE (1); IT (2); FR (2); GB (4)