Pompe Disease
Conditions
Brief summary
This is a Phase 2 open-label, multiple dose study of BMN 701 administered by IV infusion every 2 weeks (qow) to patients with late-onset Pompe disease.
Interventions
BIOLOGICALBMN 701
GILT-tagged recombinant human GAA
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have completed a prior BMN 701 clinical development study; * Have provided written informed consent after the nature of the study has been explained prior to performance of any study-related procedures. Minors may participate as long as they provide written assent after the nature of the study has been explained to them and after their parent, or legal guardian has provided written informed consent, prior to the performance of any study-related procedures; * Have been diagnosed with late-onset Pompe Disease, based on the entry criteria of a prior BMN 701 study; * If sexually active, be willing to use 2 known effective methods of contraception from Screening until 4 months after the last dose of study-drug; * If female, and not considered to be of childbearing potential, be at least 2 years post-menopausal, or have had tubal ligation at least 1 year prior to screening, or have had a total hysterectomy; * If female, and of childbearing potential, have a negative pregnancy test during the Screening Period and at the Baseline visit, and be willing to have additional pregnancy tests during the study; * Have the ability to comply with the protocol requirements, in the opinion of the Investigator.
Exclusion criteria
* Have received any experimental or approved therapy for Pompe disease, other than BMN 701, subsequent to completion of a BMN 701 study and prior to entry into POM-002; * Have received, or are anticipated to receive, any investigational medication, other than BMN 701, within 30 days prior to the first dose of study-drug; * Are breastfeeding at screening or planning to become pregnant (self or partner) at any time during the study; * Have 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Positive Anti-BMN 701 Antibody | Baseline, Week 144 | Status of Anti-BMN 701 antibody is corresponding to the test results of blood samples. |
| Number of Participants With a Positive Anti-BMN 701 Antibody Response | Baseline, Week 144 | Status of Anti-IGF-I antibody is corresponding to the test results of blood samples |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 6 Minutes Walk Test (Meters) | Baseline, Week 144 | Distance walked within 6 minutes |
| Maximum Voluntary Ventilation (MVV) | Baseline, Week 144 | Pulmonary function test: Maximum Voluntary Ventilation (MVV) |
| Percent Predicted Upright Forced Vital Capacity (FVC) | Baseline, Week 144 | Pulmonary function test: Percent Predicted Upright Forced Vital Capacity |
| Percent Predicted Maximal Inspiratory Pressure (MIP) | Baseline, Week 144 | Pulmonary Function Test: Percent Predicted Maximal Inspiratory Pressure |
| Plasma IGF-I Concentration | Baseline, Week 144 | Plasma IGF-I concentration from lab |
| Plasma IGF-II Concentration | Baseline, Week 144 | Plasma IGF-II concentration from lab |
| Insulin-like Growth Factor Binding Protein 3 (IGFBP3) | Baseline, Week 144 | insulin-like growth factor binding protein 3 from lab |
| Change From Baseline in Urine Tetrasaccharide Concentration at Week 144 | Baseline, Week 144 | Change from Baseline in Urine Tetrasaccharide Concentration at Week 144 |
| Percent Predicted Maximum Expiratory Pressure (MEP) | Baseline, Week 144 | Pulmonary Function Test: Percent Predicted Maximum Expiratory Pressure |
Countries
Australia, France, Germany, New Zealand, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BMN 701 5 mg/kg IV infusion at dose levels of 5 mg/kg | 3 |
| BMN 701 10 mg/kg IV infusion at dose levels of 10 mg/kg | 3 |
| BMN 701 20 mg/kg IV infusion at dose levels of 20 mg/kg | 15 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 2 |
| Overall Study | Other - study termination | 2 | 2 | 10 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 3 |
Baseline characteristics
| Characteristic | BMN 701 5 mg/kg | BMN 701 10 mg/kg | BMN 701 20 mg/kg | Total |
|---|---|---|---|---|
| Age, Continuous | 52.3 years STANDARD_DEVIATION 6.66 | 42.7 years STANDARD_DEVIATION 13.05 | 50.1 years STANDARD_DEVIATION 5.28 | 49.4 years STANDARD_DEVIATION 7.03 |
| Age, Customized 18-65 years | 3 Participants | 3 Participants | 15 Participants | 21 Participants |
| 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 | 15 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 3 Participants | 3 Participants | 14 Participants | 20 Participants |
| Region of Enrollment Australia | 1 Participants | 1 Participants | 4 Participants | 6 Participants |
| Region of Enrollment France | 0 Participants | 0 Participants | 1 Participants | 1 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 | 2 Participants | 2 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 6 Participants | 8 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 9 Participants | 13 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 / 15 | 0 / 21 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 15 / 15 | 21 / 21 |
| serious Total, serious adverse events | 2 / 3 | 1 / 3 | 7 / 15 | 10 / 21 |
Outcome results
Primary
Number of Participants With a Positive Anti-BMN 701 Antibody
Status of Anti-BMN 701 antibody is corresponding to the test results of blood samples.
Time frame: Baseline, Week 144
Population: Full Analysis Set. Please note the overall number of participants reflects the number of patients in that arm, while the outcome measurement number of participants reflects the number of patients for which data is available and analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMN 701 5 mg/kg | Number of Participants With a Positive Anti-BMN 701 Antibody | Baseline | 2 Participants |
| BMN 701 5 mg/kg | Number of Participants With a Positive Anti-BMN 701 Antibody | Week 144 | 2 Participants |
| BMN 701 10 mg/kg | Number of Participants With a Positive Anti-BMN 701 Antibody | Baseline | 1 Participants |
| BMN 701 10 mg/kg | Number of Participants With a Positive Anti-BMN 701 Antibody | Week 144 | 2 Participants |
| BMN 701 20 mg/kg | Number of Participants With a Positive Anti-BMN 701 Antibody | Baseline | 11 Participants |
| BMN 701 20 mg/kg | Number of Participants With a Positive Anti-BMN 701 Antibody | Week 144 | 10 Participants |
Primary
Number of Participants With a Positive Anti-BMN 701 Antibody Response
Status of Anti-IGF-I antibody is corresponding to the test results of blood samples
Time frame: Baseline, Week 144
Population: Full Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMN 701 5 mg/kg | Number of Participants With a Positive Anti-BMN 701 Antibody Response | Baseline | 0 Participants |
| BMN 701 5 mg/kg | Number of Participants With a Positive Anti-BMN 701 Antibody Response | Week 144 | 0 Participants |
| BMN 701 10 mg/kg | Number of Participants With a Positive Anti-BMN 701 Antibody Response | Baseline | 2 Participants |
| BMN 701 10 mg/kg | Number of Participants With a Positive Anti-BMN 701 Antibody Response | Week 144 | 1 Participants |
| BMN 701 20 mg/kg | Number of Participants With a Positive Anti-BMN 701 Antibody Response | Baseline | 0 Participants |
| BMN 701 20 mg/kg | Number of Participants With a Positive Anti-BMN 701 Antibody Response | Week 144 | 5 Participants |
Primary
Number of Participants With a Positive Anti-BMN 701 Antibody Response
Status of Anti-IGF-II antibody is corresponding to the test results of blood samples
Time frame: Baseline, Week 144
Population: Full Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMN 701 5 mg/kg | Number of Participants With a Positive Anti-BMN 701 Antibody Response | Baseline | 1 Participants |
| BMN 701 5 mg/kg | Number of Participants With a Positive Anti-BMN 701 Antibody Response | Week 144 | 0 Participants |
| BMN 701 10 mg/kg | Number of Participants With a Positive Anti-BMN 701 Antibody Response | Baseline | 2 Participants |
| BMN 701 10 mg/kg | Number of Participants With a Positive Anti-BMN 701 Antibody Response | Week 144 | 2 Participants |
| BMN 701 20 mg/kg | Number of Participants With a Positive Anti-BMN 701 Antibody Response | Baseline | 2 Participants |
| BMN 701 20 mg/kg | Number of Participants With a Positive Anti-BMN 701 Antibody Response | Week 144 | 7 Participants |
Secondary
6 Minutes Walk Test (Meters)
Distance walked within 6 minutes
Time frame: Baseline, Week 144
Population: Full Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN 701 5 mg/kg | 6 Minutes Walk Test (Meters) | Baseline | 334 meter | Standard Deviation 227.119 |
| BMN 701 5 mg/kg | 6 Minutes Walk Test (Meters) | Change from Baseline to Week 144 | -36 meter | Standard Deviation 90.508 |
| BMN 701 10 mg/kg | 6 Minutes Walk Test (Meters) | Baseline | 360 meter | Standard Deviation 51.403 |
| BMN 701 10 mg/kg | 6 Minutes Walk Test (Meters) | Change from Baseline to Week 144 | -120.75 meter | Standard Deviation 67.529 |
| BMN 701 20 mg/kg | 6 Minutes Walk Test (Meters) | Baseline | 363.8 meter | Standard Deviation 157.818 |
| BMN 701 20 mg/kg | 6 Minutes Walk Test (Meters) | Change from Baseline to Week 144 | 9.5 meter | Standard Deviation 77.572 |
Secondary
Change From Baseline in Urine Tetrasaccharide Concentration at Week 144
Change from Baseline in Urine Tetrasaccharide Concentration at Week 144
Time frame: Baseline, Week 144
Population: Full Analysis Set. No data collected for outcomes with 0 participants analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BMN 701 10 mg/kg | Change From Baseline in Urine Tetrasaccharide Concentration at Week 144 | -0.2 mmol/mol | Standard Deviation 3.394 |
| BMN 701 20 mg/kg | Change From Baseline in Urine Tetrasaccharide Concentration at Week 144 | -1.07 mmol/mol | Standard Deviation 0.975 |
Secondary
Insulin-like Growth Factor Binding Protein 3 (IGFBP3)
insulin-like growth factor binding protein 3 from lab
Time frame: Baseline, Week 144
Population: Full Analysis Set. No data collected for outcomes with 0 participants analyzed. Please note: the overall number of participants reflects the number of patients in that arm, while the outcome measurement number of participants reflects the number of patients for which data is available and analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN 701 5 mg/kg | Insulin-like Growth Factor Binding Protein 3 (IGFBP3) | Week 144 | 157.33 nmol/L | Standard Deviation 41.477 |
| BMN 701 10 mg/kg | Insulin-like Growth Factor Binding Protein 3 (IGFBP3) | Week 144 | 209 nmol/L | Standard Deviation 39.598 |
| BMN 701 20 mg/kg | Insulin-like Growth Factor Binding Protein 3 (IGFBP3) | Baseline | 150.45 nmol/L | Standard Deviation 23.914 |
| BMN 701 20 mg/kg | Insulin-like Growth Factor Binding Protein 3 (IGFBP3) | Week 144 | 146.64 nmol/L | Standard Deviation 33.587 |
Secondary
Maximum Voluntary Ventilation (MVV)
Pulmonary function test: Maximum Voluntary Ventilation (MVV)
Time frame: Baseline, Week 144
Population: Full Analysis Set. No data collected for outcomes with 0 participants analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN 701 10 mg/kg | Maximum Voluntary Ventilation (MVV) | Baseline | 76 L/min | Standard Deviation 41.037 |
| BMN 701 10 mg/kg | Maximum Voluntary Ventilation (MVV) | Change from Baseline to Week 144 | 13.5 L/min | Standard Deviation 13.435 |
| BMN 701 20 mg/kg | Maximum Voluntary Ventilation (MVV) | Baseline | 68.08 L/min | Standard Deviation 26.74 |
| BMN 701 20 mg/kg | Maximum Voluntary Ventilation (MVV) | Change from Baseline to Week 144 | 2.24 L/min | Standard Deviation 11.635 |
Secondary
Percent Predicted Maximal Inspiratory Pressure (MIP)
Pulmonary Function Test: Percent Predicted Maximal Inspiratory Pressure
Time frame: Baseline, Week 144
Population: Full Analysis Set. No data collected for outcomes with 0 participants analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN 701 10 mg/kg | Percent Predicted Maximal Inspiratory Pressure (MIP) | Baseline | 39.53 Percent of Predicted | Standard Deviation 21.868 |
| BMN 701 10 mg/kg | Percent Predicted Maximal Inspiratory Pressure (MIP) | Change from Baseline to Week 144 | 21.17 Percent of Predicted | Standard Deviation 14.537 |
| BMN 701 20 mg/kg | Percent Predicted Maximal Inspiratory Pressure (MIP) | Baseline | 40.2 Percent of Predicted | Standard Deviation 25.863 |
| BMN 701 20 mg/kg | Percent Predicted Maximal Inspiratory Pressure (MIP) | Change from Baseline to Week 144 | 18.48 Percent of Predicted | Standard Deviation 18.599 |
Secondary
Percent Predicted Maximum Expiratory Pressure (MEP)
Pulmonary Function Test: Percent Predicted Maximum Expiratory Pressure
Time frame: Baseline, Week 144
Population: Full Analysis Set. No data collected for outcomes with 0 participants analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN 701 10 mg/kg | Percent Predicted Maximum Expiratory Pressure (MEP) | Baseline | 31.07 Percent of Predicted | Standard Deviation 6.641 |
| BMN 701 10 mg/kg | Percent Predicted Maximum Expiratory Pressure (MEP) | Change from Baseline to Week 144 | -0.28 Percent of Predicted | Standard Deviation 5.841 |
| BMN 701 20 mg/kg | Percent Predicted Maximum Expiratory Pressure (MEP) | Baseline | 36.7 Percent of Predicted | Standard Deviation 15.939 |
| BMN 701 20 mg/kg | Percent Predicted Maximum Expiratory Pressure (MEP) | Change from Baseline to Week 144 | 5.11 Percent of Predicted | Standard Deviation 16.395 |
Secondary
Percent Predicted Upright Forced Vital Capacity (FVC)
Pulmonary function test: Percent Predicted Upright Forced Vital Capacity
Time frame: Baseline, Week 144
Population: Full Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN 701 5 mg/kg | Percent Predicted Upright Forced Vital Capacity (FVC) | Baseline | 69.33 Percent Predicted | Standard Deviation 19.732 |
| BMN 701 5 mg/kg | Percent Predicted Upright Forced Vital Capacity (FVC) | Change from Baseline to Week 144 | -8.33 Percent Predicted | Standard Deviation 7.095 |
| BMN 701 10 mg/kg | Percent Predicted Upright Forced Vital Capacity (FVC) | Baseline | 67.33 Percent Predicted | Standard Deviation 26.577 |
| BMN 701 10 mg/kg | Percent Predicted Upright Forced Vital Capacity (FVC) | Change from Baseline to Week 144 | -0.5 Percent Predicted | Standard Deviation 4.95 |
| BMN 701 20 mg/kg | Percent Predicted Upright Forced Vital Capacity (FVC) | Baseline | 57.13 Percent Predicted | Standard Deviation 18.677 |
| BMN 701 20 mg/kg | Percent Predicted Upright Forced Vital Capacity (FVC) | Change from Baseline to Week 144 | -2 Percent Predicted | Standard Deviation 8 |
Secondary
Percent Predicted Upright Forced Vital Capacity (FVC)
Pulmonary function test: Percent Predicted Upright Forced Vital capacity
Time frame: Baseline, Week 144
Population: Full Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN 701 5 mg/kg | Percent Predicted Upright Forced Vital Capacity (FVC) | Baseline | 36.67 Percent Predicted | Standard Deviation 17.954 |
| BMN 701 5 mg/kg | Percent Predicted Upright Forced Vital Capacity (FVC) | Change from Baseline to Week 144 | -4.33 Percent Predicted | Standard Deviation 9.452 |
| BMN 701 10 mg/kg | Percent Predicted Upright Forced Vital Capacity (FVC) | Baseline | 47.67 Percent Predicted | Standard Deviation 32.578 |
| BMN 701 10 mg/kg | Percent Predicted Upright Forced Vital Capacity (FVC) | Change from Baseline to Week 144 | 4.5 Percent Predicted | Standard Deviation 26.163 |
| BMN 701 20 mg/kg | Percent Predicted Upright Forced Vital Capacity (FVC) | Baseline | 44.25 Percent Predicted | Standard Deviation 21.55 |
| BMN 701 20 mg/kg | Percent Predicted Upright Forced Vital Capacity (FVC) | Change from Baseline to Week 144 | -3.43 Percent Predicted | Standard Deviation 6.901 |
Secondary
Plasma IGF-I Concentration
Plasma IGF-I concentration from lab
Time frame: Baseline, Week 144
Population: Full Analysis Set. No data collected for outcomes with 0 participants analyzed. Please note: the overall number of participants reflects the number of patients in that arm, while the outcome measurement number of participants reflects the number of patients for which data is available and analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN 701 5 mg/kg | Plasma IGF-I Concentration | Week 144 | 26.98 nmol/L | Standard Deviation 1.379 |
| BMN 701 10 mg/kg | Plasma IGF-I Concentration | Week 144 | 18.4 nmol/L | Standard Deviation 7.078 |
| BMN 701 20 mg/kg | Plasma IGF-I Concentration | Baseline | 20.26 nmol/L | Standard Deviation 6.465 |
| BMN 701 20 mg/kg | Plasma IGF-I Concentration | Week 144 | 17.62 nmol/L | Standard Deviation 5.878 |
Secondary
Plasma IGF-II Concentration
Plasma IGF-II concentration from lab
Time frame: Baseline, Week 144
Population: Full Analysis Set. No data collected for outcomes with 0 participants analyzed. Please note: the overall number of participants reflects the number of patients in that arm, while the outcome measurement number of participants reflects the number of patients for which data is available and analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN 701 5 mg/kg | Plasma IGF-II Concentration | Week 144 | 467.67 nmol/L | Standard Deviation 117.142 |
| BMN 701 10 mg/kg | Plasma IGF-II Concentration | Baseline | 702 nmol/L | Standard Deviation 0 |
| BMN 701 10 mg/kg | Plasma IGF-II Concentration | Week 144 | 559.5 nmol/L | Standard Deviation 140.714 |
| BMN 701 20 mg/kg | Plasma IGF-II Concentration | Baseline | 496.83 nmol/L | Standard Deviation 113.417 |
| BMN 701 20 mg/kg | Plasma IGF-II Concentration | Week 144 | 698.82 nmol/L | Standard Deviation 228.948 |