Late-onset Pompe Disease
Conditions
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.
Interventions
DRUGBMN 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).
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Predicted Maximum Inspiratory Pressure (MIP) | Baseline, Week 24 | Pulmonary function test: Percent Predicted Maximum Inspiratory Pressure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Predicted Maximum Expiratory Pressure (MEP) | Baseline, Week 24 | Pulmonary function test: Percent Predicted Maximum Expiratory Pressure |
| 6 Minute Walk Test (Meters) | Baseline, Week 24 | Distance walked within 6 minutes |
| Percent Predicted Upright Forced Vital Capacity (FVC) | Baseline, Week 24 | Pulmonary function test: Percent Predicted Upright Forced Vital Capacity |
| Number of Participants With Non-Serious AEs | Baseline through Week 24 +4 weeks follow-up | 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. |
Countries
Belgium, France, Germany, Italy, Netherlands, Portugal, United Kingdom, United States
Participant flow
Pre-assignment details
The study consisted of a 31-day Screening and Baseline Period (26-day Screening Period, a 5-day Baseline/Enrollment Period), a 24-week Treatment Period, and a 30-day Safety Follow-up Period. Following the Screening and Baseline assessments, qualified subjects were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| BMN 701 20 mg/kg BMN 701 20 mg/kg | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | BMN 701 20 mg/kg |
|---|---|
| Age, Continuous | 47.9 years STANDARD_DEVIATION 13.27 |
| Age, Customized 18-65 | 22 Participants |
| Age, Customized > 65 | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants |
| Race/Ethnicity, Customized White | 24 Participants |
| Region of Enrollment Belgium | 1 Participants |
| Region of Enrollment Germany | 9 Participants |
| Region of Enrollment United Kingdom | 7 Participants |
| Region of Enrollment United States | 7 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 24 |
| other Total, other adverse events | 23 / 24 |
| serious Total, serious adverse events | 10 / 24 |
Outcome results
Primary
Percent Predicted Maximum Inspiratory Pressure (MIP)
Pulmonary function test: Percent Predicted Maximum Inspiratory Pressure
Time frame: Baseline, Week 24
Population: Full Analysis Set. Please note the Overall Number of Participants reflects the number of patients in the Analysis Population, while the Number Analyzed of patients at specific visit in the Outcome Measure Table reflects the participants who had data at that visit .
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN701 20 mg/kg | Percent Predicted Maximum Inspiratory Pressure (MIP) | Baseline | 50.0 Percent Predicted | Standard Deviation 17.5 |
| BMN701 20 mg/kg | Percent Predicted Maximum Inspiratory Pressure (MIP) | Change from Baseline to Week 24 | 2.2 Percent Predicted | Standard Deviation 8.3 |
Secondary
6 Minute Walk Test (Meters)
Distance walked within 6 minutes
Time frame: Baseline, Week 24
Population: Full Analysis Set. Please note the Overall Number of Participants reflects the number of patients in the Analysis Population, while the Number Analyzed of patients at specific visit in the Outcome Measure Table reflects the participants who had data at that visit .
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN701 20 mg/kg | 6 Minute Walk Test (Meters) | Baseline | 345.8 Meter | Standard Deviation 95.3 |
| BMN701 20 mg/kg | 6 Minute Walk Test (Meters) | Change from Baseline to Week 24 | 26.1 Meter | Standard Deviation 40.6 |
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.
Time frame: Baseline through Week 24 +4 weeks follow-up
Population: Full Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BMN701 20 mg/kg | Number of Participants With Non-Serious AEs | 23 Participants |
Secondary
Percent Predicted Maximum Expiratory Pressure (MEP)
Pulmonary function test: Percent Predicted Maximum Expiratory Pressure
Time frame: Baseline, Week 24
Population: Full Analysis Set. Please note the Overall Number of Participants reflects the number of patients in the Analysis Population, while the Number Analyzed of patients at specific visit in the Outcome Measure Table reflects the participants who had data at that visit .
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN701 20 mg/kg | Percent Predicted Maximum Expiratory Pressure (MEP) | Baseline | 38.9 Percent Predicted | Standard Deviation 12.3 |
| BMN701 20 mg/kg | Percent Predicted Maximum Expiratory Pressure (MEP) | Change from Baseline to Week 24 | 3.1 Percent Predicted | Standard Deviation 8.7 |
Secondary
Percent Predicted Upright Forced Vital Capacity (FVC)
Pulmonary function test: Percent Predicted Upright Forced Vital Capacity
Time frame: Baseline, Week 24
Population: Full Analysis Set. Please note the Overall Number of Participants reflects the number of patients in the Analysis Population, while the Number Analyzed of patients at specific visit in the Outcome Measure Table reflects the participants who had data at that visit .
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN701 20 mg/kg | Percent Predicted Upright Forced Vital Capacity (FVC) | Baseline | 60.7 Percent Predicted | Standard Deviation 15.1 |
| BMN701 20 mg/kg | Percent Predicted Upright Forced Vital Capacity (FVC) | Change from Baseline to Week 24 | -3.7 Percent Predicted | Standard Deviation 4.4 |