Pompe Disease
Conditions
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.
Interventions
BIOLOGICALBMN 701
GILT-tagged recombinant human GAA
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | 24 weeks | Number of Participants with Adverse Events as a Measure of Safety and Tolerability |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Six Minutes Walk Test | 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
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure | 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. |
| Change From Baseline in Percent Predicted Upright Forced Vital Capacity | 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. |
| Change From Baseline in Upright Maximum Ventilatory Volume | 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. |
| Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure | 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. |
| Change From Baseline in Percent Predicted Supine Forced Vital Capacity | 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. |
Countries
Australia, France, Germany, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BMN 701 5 mg/kg BMN 701 5 mg/kg IV | 3 |
| BMN 701 10 mg/kg BMN 701 10 mg/kg IV | 3 |
| BMN 701 20 mg/kg BMN 701 20 mg/kg IV | 16 |
| Total | 22 |
Baseline characteristics
| Characteristic | BMN 701 5 mg/kg | BMN 701 10 mg/kg | BMN 701 20 mg/kg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 16 Participants | 22 Participants |
| Age, Continuous | 51.7 years STANDARD_DEVIATION 6.81 | 42.3 years STANDARD_DEVIATION 12.9 | 50.1 years STANDARD_DEVIATION 5.37 | 49.3 years STANDARD_DEVIATION 7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 2 Participants | 16 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 3 Participants | 15 Participants | 21 Participants |
| Region of Enrollment Australia | 0 Participants | 0 Participants | 4 Participants | 4 Participants |
| Region of Enrollment France | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Region of Enrollment Germany | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United Kingdom | 0 Participants | 0 Participants | 6 Participants | 6 Participants |
| Region of Enrollment United States | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 6 Participants | 8 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 10 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 16 | 0 / 22 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 15 / 16 | 21 / 22 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 4 / 16 | 4 / 22 |
Outcome results
Primary
Number of Participants With Adverse Events
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: 24 weeks
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BMN 701 5 mg/kg | Number of Participants With Adverse Events | 3 Participants |
| BMN 701 10 mg/kg | Number of Participants With Adverse Events | 3 Participants |
| BMN 701 20 mg/kg | Number of Participants With Adverse Events | 15 Participants |
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
Time frame: Baseline up to 24 weeks
Population: ITT Population. As some patients did not attend or all tests were not completed at each visit, some time points had different numbers of patients analyzed. The total number of patients analyzed for each arm is listed as the maximum patients analyzed at any given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN 701 5 mg/kg | Change From Baseline in Six Minutes Walk Test | Change from Baseline - Week 18 | 43.3 meter | Standard Deviation 89.44 |
| BMN 701 5 mg/kg | Change From Baseline in Six Minutes Walk Test | Change from Baseline - Week 6 | -2.5 meter | Standard Deviation 23.33 |
| BMN 701 5 mg/kg | Change From Baseline in Six Minutes Walk Test | Change from Baseline - Week 24 | 36.0 meter | Standard Deviation 76.02 |
| BMN 701 5 mg/kg | Change From Baseline in Six Minutes Walk Test | Change from Baseline - Week 12 | 31.2 meter | Standard Deviation 78.81 |
| BMN 701 5 mg/kg | Change From Baseline in Six Minutes Walk Test | Baseline | 334 meter | Standard Deviation 227.12 |
| BMN 701 10 mg/kg | Change From Baseline in Six Minutes Walk Test | Change from Baseline - Week 12 | -13.7 meter | Standard Deviation 8.04 |
| BMN 701 10 mg/kg | Change From Baseline in Six Minutes Walk Test | Change from Baseline - Week 18 | -79.0 meter | Standard Deviation 104.61 |
| BMN 701 10 mg/kg | Change From Baseline in Six Minutes Walk Test | Change from Baseline - Week 24 | -42.7 meter | Standard Deviation 12.57 |
| BMN 701 10 mg/kg | Change From Baseline in Six Minutes Walk Test | Change from Baseline - Week 6 | -30.3 meter | Standard Deviation 56.5 |
| BMN 701 10 mg/kg | Change From Baseline in Six Minutes Walk Test | Baseline | 360 meter | Standard Deviation 51.4 |
| BMN 701 20 mg/kg | Change From Baseline in Six Minutes Walk Test | Change from Baseline - Week 12 | 11.1 meter | Standard Deviation 42.67 |
| BMN 701 20 mg/kg | Change From Baseline in Six Minutes Walk Test | Baseline | 354.5 meter | Standard Deviation 156.94 |
| BMN 701 20 mg/kg | Change From Baseline in Six Minutes Walk Test | Change from Baseline - Week 6 | 19.8 meter | Standard Deviation 35.11 |
| BMN 701 20 mg/kg | Change From Baseline in Six Minutes Walk Test | Change from Baseline - Week 18 | 16.4 meter | Standard Deviation 55.09 |
| BMN 701 20 mg/kg | Change From Baseline in Six Minutes Walk Test | Change from Baseline - Week 24 | 22.3 meter | Standard Deviation 54.23 |
| Total | Change From Baseline in Six Minutes Walk Test | Change from Baseline - Week 18 | 6.6 meter | Standard Deviation 73.43 |
| Total | Change From Baseline in Six Minutes Walk Test | Change from Baseline - Week 6 | 10.5 meter | Standard Deviation 40.08 |
| Total | Change From Baseline in Six Minutes Walk Test | Baseline | 352.5 meter | Standard Deviation 151.05 |
| Total | Change From Baseline in Six Minutes Walk Test | Change from Baseline - Week 12 | 10.4 meter | Standard Deviation 45.32 |
| Total | Change From Baseline in Six Minutes Walk Test | Change from Baseline - Week 24 | 15.3 meter | Standard Deviation 56.97 |
Other Pre-specified
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.
Time frame: Baseline up to 24 weeks
Population: ITT Population. As some patients did not attend or all tests were not completed at each visit, some time points had different numbers of patients analyzed. The total number of patients analyzed for each arm is listed as the maximum patients analyzed at any given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN 701 5 mg/kg | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Change from Baseline - Week 18 | 1.3 percentage of Predicted Supine FVC | Standard Deviation 1.53 |
| BMN 701 5 mg/kg | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Change from Baseline - Week 6 | 2.1 percentage of Predicted Supine FVC | Standard Deviation 1.2 |
| BMN 701 5 mg/kg | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Change from Baseline - Week 24 | 2.0 percentage of Predicted Supine FVC | Standard Deviation 3 |
| BMN 701 5 mg/kg | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Change from Baseline - Week 12 | 0.3 percentage of Predicted Supine FVC | Standard Deviation 4.22 |
| BMN 701 5 mg/kg | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Baseline | 36.7 percentage of Predicted Supine FVC | Standard Deviation 17.95 |
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Change from Baseline - Week 12 | -4.7 percentage of Predicted Supine FVC | Standard Deviation 2.89 |
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Change from Baseline - Week 18 | -1.3 percentage of Predicted Supine FVC | Standard Deviation 6.66 |
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Change from Baseline - Week 24 | -3.3 percentage of Predicted Supine FVC | Standard Deviation 5.51 |
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Change from Baseline - Week 6 | -1.3 percentage of Predicted Supine FVC | Standard Deviation 4.04 |
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Baseline | 47.7 percentage of Predicted Supine FVC | Standard Deviation 32.58 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Change from Baseline - Week 12 | 3.3 percentage of Predicted Supine FVC | Standard Deviation 3.87 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Baseline | 46.3 percentage of Predicted Supine FVC | Standard Deviation 21.93 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Change from Baseline - Week 6 | -0.8 percentage of Predicted Supine FVC | Standard Deviation 4.86 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Change from Baseline - Week 18 | 2.3 percentage of Predicted Supine FVC | Standard Deviation 3.14 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Change from Baseline - Week 24 | 1.1 percentage of Predicted Supine FVC | Standard Deviation 4.42 |
| Total | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Change from Baseline - Week 18 | 1.5 percentage of Predicted Supine FVC | Standard Deviation 3.7 |
| Total | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Change from Baseline - Week 6 | -0.6 percentage of Predicted Supine FVC | Standard Deviation 4.44 |
| Total | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Baseline | 45 percentage of Predicted Supine FVC | Standard Deviation 22.1 |
| Total | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Change from Baseline - Week 12 | 1.5 percentage of Predicted Supine FVC | Standard Deviation 4.7 |
| Total | Change From Baseline in Percent Predicted Supine Forced Vital Capacity | Change from Baseline - Week 24 | 0.5 percentage of Predicted Supine FVC | Standard Deviation 4.53 |
Other Pre-specified
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.
Time frame: Baseline up to 24 week
Population: ITT Population. As some patients did not attend or all tests were not completed at each visit, some time points had different numbers of patients analyzed. The total number of patients analyzed for each arm is listed as the maximum patients analyzed at any given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN 701 5 mg/kg | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Baseline | 69.3 percentage of Predicted Upright FVC | Standard Deviation 19.73 |
| BMN 701 5 mg/kg | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Change from Baseline - Week 24 | 1.0 percentage of Predicted Upright FVC | Standard Deviation 2.65 |
| BMN 701 5 mg/kg | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Change from Baseline - Week 12 | -2.6 percentage of Predicted Upright FVC | Standard Deviation 9.5 |
| BMN 701 5 mg/kg | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Change from Baseline - Week 6 | 4.0 percentage of Predicted Upright FVC | Standard Deviation 4.24 |
| BMN 701 5 mg/kg | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Change from Baseline - Week 18 | 1.5 percentage of Predicted Upright FVC | Standard Deviation 4.09 |
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Change from Baseline - Week 12 | -3.7 percentage of Predicted Upright FVC | Standard Deviation 2.89 |
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Change from Baseline - Week 6 | -2.0 percentage of Predicted Upright FVC | Standard Deviation 2.65 |
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Change from Baseline - Week 24 | -1.7 percentage of Predicted Upright FVC | Standard Deviation 3.06 |
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Change from Baseline - Week 18 | 0.3 percentage of Predicted Upright FVC | Standard Deviation 3.06 |
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Baseline | 67.3 percentage of Predicted Upright FVC | Standard Deviation 26.58 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Change from Baseline - Week 18 | 1.2 percentage of Predicted Upright FVC | Standard Deviation 4.49 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Baseline | 58.1 percentage of Predicted Upright FVC | Standard Deviation 18.42 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Change from Baseline - Week 12 | 1.6 percentage of Predicted Upright FVC | Standard Deviation 4.35 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Change from Baseline - Week 6 | 0.4 percentage of Predicted Upright FVC | Standard Deviation 3.3 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Change from Baseline - Week 24 | 1.2 percentage of Predicted Upright FVC | Standard Deviation 3.89 |
| Total | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Change from Baseline - Week 24 | 0.8 percentage of Predicted Upright FVC | Standard Deviation 3.65 |
| Total | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Baseline | 60.9 percentage of Predicted Upright FVC | Standard Deviation 19.21 |
| Total | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Change from Baseline - Week 6 | 0.4 percentage of Predicted Upright FVC | Standard Deviation 3.46 |
| Total | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Change from Baseline - Week 12 | 0.3 percentage of Predicted Upright FVC | Standard Deviation 5.25 |
| Total | Change From Baseline in Percent Predicted Upright Forced Vital Capacity | Change from Baseline - Week 18 | 1.1 percentage of Predicted Upright FVC | Standard Deviation 4.1 |
Other Pre-specified
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.
Time frame: Baseline up to 24 weeks
Population: ITT Population. As some patients did not attend or all tests were not completed at each visit, some time points had different numbers of patients analyzed. The total number of patients analyzed for each arm is listed as the maximum patients analyzed at any given time point. No patient had baseline assessment in group of BMN 701 5 mg/kg.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure | Change from Baseline - Week 12 | 1.4 percentage of Predicted MEP | Standard Deviation 4.53 |
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure | Change from Baseline - Week 6 | 6.8 percentage of Predicted MEP | Standard Deviation 4.06 |
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure | Change from Baseline - Week 24 | 2.5 percentage of Predicted MEP | Standard Deviation 10.4 |
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure | Baseline | 31.1 percentage of Predicted MEP | Standard Deviation 6.64 |
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure | Change from Baseline - Week 18 | 1.2 percentage of Predicted MEP | Standard Deviation 2.06 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure | Baseline | 36.3 percentage of Predicted MEP | Standard Deviation 15.46 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure | Change from Baseline - Week 24 | 5.2 percentage of Predicted MEP | Standard Deviation 8.25 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure | Change from Baseline - Week 18 | 6.9 percentage of Predicted MEP | Standard Deviation 7.21 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure | Change from Baseline - Week 12 | 2.2 percentage of Predicted MEP | Standard Deviation 8.68 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure | Change from Baseline - Week 6 | 3.2 percentage of Predicted MEP | Standard Deviation 5.38 |
| Total | Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure | Change from Baseline - Week 24 | 4.8 percentage of Predicted MEP | Standard Deviation 8.36 |
| Total | Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure | Change from Baseline - Week 12 | 2.0 percentage of Predicted MEP | Standard Deviation 8.07 |
| Total | Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure | Change from Baseline - Week 18 | 6.0 percentage of Predicted MEP | Standard Deviation 6.94 |
| Total | Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure | Change from Baseline - Week 6 | 3.8 percentage of Predicted MEP | Standard Deviation 5.27 |
| Total | Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure | Baseline | 35.5 percentage of Predicted MEP | Standard Deviation 14.42 |
Other Pre-specified
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.
Time frame: Baseline up to 24 weeks
Population: ITT Population. As some patients did not attend or all tests were not completed at each visit, some time points had different numbers of patients analyzed. The total number of patients analyzed for each arm is listed as the maximum patients analyzed at any given time point. No patient had baseline assessment in group of BMN 701 5 mg/kg.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure | Change from baseline at week 24 | 0.7 percentage of Predicted MIP | Standard Deviation 6.69 |
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure | Change from baseline at week 6 | 1.7 percentage of Predicted MIP | Standard Deviation 1.46 |
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure | Change from baseline at week 18 | 2.9 percentage of Predicted MIP | Standard Deviation 11.77 |
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure | Baseline | 39.5 percentage of Predicted MIP | Standard Deviation 21.87 |
| BMN 701 10 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure | Change from baseline at week 12 | 3.4 percentage of Predicted MIP | Standard Deviation 6.74 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure | Baseline | 40.5 percentage of Predicted MIP | Standard Deviation 25.01 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure | Change from baseline at week 24 | 11.1 percentage of Predicted MIP | Standard Deviation 8.31 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure | Change from baseline at week 12 | 11.4 percentage of Predicted MIP | Standard Deviation 10.92 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure | Change from baseline at week 6 | 5.3 percentage of Predicted MIP | Standard Deviation 9.8 |
| BMN 701 20 mg/kg | Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure | Change from baseline at week 18 | 14.5 percentage of Predicted MIP | Standard Deviation 14.48 |
| Total | Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure | Change from baseline at week 24 | 9.5 percentage of Predicted MIP | Standard Deviation 8.81 |
| Total | Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure | Change from baseline at week 6 | 4.7 percentage of Predicted MIP | Standard Deviation 9.06 |
| Total | Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure | Change from baseline at week 12 | 10.1 percentage of Predicted MIP | Standard Deviation 10.65 |
| Total | Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure | Change from baseline at week 18 | 12.6 percentage of Predicted MIP | Standard Deviation 14.45 |
| Total | Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure | Baseline | 40.3 percentage of Predicted MIP | Standard Deviation 23.97 |
Other Pre-specified
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.
Time frame: Baseline up to 24 weeks
Population: ITT Population. As some patients did not attend or all tests were not completed at each visit, some time points had different numbers of patients analyzed. The total number of patients analyzed for each arm is listed as the maximum patients analyzed at any given time point. No patient had baseline assessment in group of BMN 701 5 mg/kg.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN 701 10 mg/kg | Change From Baseline in Upright Maximum Ventilatory Volume | Change from Baseline - Week 18 | -3.9 L/min | Standard Deviation 2.86 |
| BMN 701 10 mg/kg | Change From Baseline in Upright Maximum Ventilatory Volume | Change from Baseline - Week 12 | -1.1 L/min | Standard Deviation 2.73 |
| BMN 701 10 mg/kg | Change From Baseline in Upright Maximum Ventilatory Volume | Baseline | 76 L/min | Standard Deviation 41.04 |
| BMN 701 10 mg/kg | Change From Baseline in Upright Maximum Ventilatory Volume | Change from Baseline - Week 6 | -1.0 L/min | Standard Deviation 0.35 |
| BMN 701 10 mg/kg | Change From Baseline in Upright Maximum Ventilatory Volume | Change from Baseline - Week 24 | -0.7 L/min | Standard Deviation 9.1 |
| BMN 701 20 mg/kg | Change From Baseline in Upright Maximum Ventilatory Volume | Baseline | 67.6 L/min | Standard Deviation 25.9 |
| BMN 701 20 mg/kg | Change From Baseline in Upright Maximum Ventilatory Volume | Change from Baseline - Week 6 | 1.5 L/min | Standard Deviation 11.1 |
| BMN 701 20 mg/kg | Change From Baseline in Upright Maximum Ventilatory Volume | Change from Baseline - Week 12 | 3.8 L/min | Standard Deviation 11.64 |
| BMN 701 20 mg/kg | Change From Baseline in Upright Maximum Ventilatory Volume | Change from Baseline - Week 18 | 4.7 L/min | Standard Deviation 10.89 |
| BMN 701 20 mg/kg | Change From Baseline in Upright Maximum Ventilatory Volume | Change from Baseline - Week 24 | 2.3 L/min | Standard Deviation 10.71 |
| Total | Change From Baseline in Upright Maximum Ventilatory Volume | Change from Baseline - Week 24 | 1.8 L/min | Standard Deviation 10.28 |
| Total | Change From Baseline in Upright Maximum Ventilatory Volume | Change from Baseline - Week 18 | 3.3 L/min | Standard Deviation 10.46 |
| Total | Change From Baseline in Upright Maximum Ventilatory Volume | Baseline | 68.9 L/min | Standard Deviation 27.5 |
| Total | Change From Baseline in Upright Maximum Ventilatory Volume | Change from Baseline - Week 12 | 3.0 L/min | Standard Deviation 10.82 |
| Total | Change From Baseline in Upright Maximum Ventilatory Volume | Change from Baseline - Week 6 | 1.1 L/min | Standard Deviation 10.18 |