Pompe Disease
Conditions
Keywords
Pompe, rhGAA
Brief summary
This is an international, multi-center, open-label study designed to evaluate if the co-administration of investigational new drugs ATB200 and AT2221 is safe in adults with Pompe disease.
Detailed description
This is an open-label, fixed-sequence, ascending-dose, first-in-human study to evaluate the effect of a highly targeted rhGAA (ATB200) co-administered with an enzyme stabilizer (AT2221). The study aims to evaluate safety, tolerability, pharmacokinetics (PK), efficacy, pharmacodynamics (PD), and immunogenicity of ATB200 co-administered with AT2221. Stage 1: evaluation of safety, tolerability, and PK following sequential single ascending doses of intravenously infused ATB200 Stage 2: evaluation of safety, tolerability, and PK following single- and multiple-ascending dose combinations of ATB200 and AT2221 Stage 3: evaluation of long term safety, tolerability, and efficacy following 24 month treatment of ATB200 co-administered with AT2221 Stage 4: open-label extension period with functional assessments every 6 months
Sponsors
Amicus Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Adults with Diagnosis of Pompe disease Cohort 1: Enzyme Replacement Therapy (ERT)-experienced subject (ambulatory): * Male and female subjects between 18 and 65 years of age, inclusive * Received ERT with alglucosidase alfa (Myozyme/Lumizyme) for the previous 2-6 years, inclusive * Was receiving alglucosidase alfa at a frequency of once every other week * Must have been able to walk 200-500 meters on the 6-Minute Walk Test (6MWT) * Had upright Forced Vial Capacity (FVC) 30-80% of predicted normal value Cohort 2: ERT-experienced subjects (non-ambulatory): * Male and female subjects between 18 and 65 years of age, inclusive * Had been receiving ERT with alglucosidase alfa for ≥2 years at a regular or set frequency * Was wheelchair-bound Cohort 3: ERT-naïve subjects (ambulatory): * Male and female subjects between 18 and 65 years of age, inclusive * Must have been able to walk 200-500 meters on the 6MWT * Had upright FVC 30-80% of predicted normal value Cohort 4: ERT-experienced subject (ambulatory): * Male and female subjects between 18 and 75 years of age, inclusive * Had been receiving ERT with alglucosidase alfa for ≥7 years, inclusive * Was receiving alglucosidase alfa at a frequency of once every other week * Must have been able to walk 75-600 meters on the 6MWT * Had upright FVC 30-85% of predicted normal value
Exclusion criteria
* Received treatment with prohibited medications within 30 days of Baseline Visit * Subject, if female, was pregnant or breastfeeding at screening * Subject, whether male or female, planned to conceive a child during the study * Had a medical or any other extenuating condition or circumstance that may, in opinion of investigator, pose an undue safety risk to the subject or compromise his/her ability to comply with protocol requirements * Had a history of allergy or sensitivity to alglucosidase alfa, miglustat or other iminosugars (Cohorts 1, 2, and 4) * Required invasive ventilatory support, or used noninvasive ventilatory support ≥ 6 hours a day while awake (Cohorts 1, 3, and 4) * Had active systemic autoimmune disease such as lupus, scleroderma, or rheumatoid arthritis; subjects with autoimmune disease must have been discussed with the Amicus Medical Monitor * Had active bronchial asthma; subjects with bronchial asthma must have been discussed with the Amicus Medical Monitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events (AEs) Leading to Discontinuation of Study Drug | Stage 3 (2 year treatment) and Stage 4 (Extension) combined, (mean = 71 months on treatment) | Number of subjects with TEAE, TESAE, and AE leading to discontinuation during the 2 year treatment period and extension (Stage 3 and 4 combined) |
| Plasma Human Acid α-glucosidase (GAA) Activity Levels as Measured by Maximum Observed Plasma Concentration (Cmax). | 18 Weeks | Plasma GAA levels (Cmax) measured in Cohorts 1 and 3 following 1st and 3rd doses of cipaglucosidase alfa + miglustat |
| Plasma GAA Activity Levels as Measured by Time to Reach the Maximum Observed Plasma Concentration (Tmax). | 18 Weeks | Plasma GAA levels (Tmax) measured in Cohorts 1 and 3 following 1st and 3rd doses of cipaglucosidase alfa + miglustat |
| Plasma GAA Activity Levels as Measured by Area Under the Plasma Drug Concentration-time Curve (AUC). | 18 Weeks | Plasma GAA levels (AUC) measured in Cohorts 1 and 3 following 1st and 3rd doses of cipaglucosidase alfa + miglustat |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Overall Physical Wellbeing (Subject's Global Impression of Change [SGIC], Question1) | Baseline, Month 60 | The Subject's Global Impression of Change overall physical wellbeing (question 1) is scored on a 7-point rating scale. Improved = response of 5 or higher, No change = response of 4, and Declined = response of 3 or lower. |
| Change From Baseline in 6-minute Walk Distance (6MWD) | Baseline, Month 60 | Motor function was measured in ambulatory subjects using 6MWD (meters). |
| Change From Baseline in Overall Physical Wellbeing (Physician's Global Impression of Change [PGIC]) | Baseline, Month 60 | The Physician's Global Impression of Change overall physical wellbeing is scored on a 7-point rating scale. Improved = response of 5 or higher, No change = response of 4, and Declined = response of 3 or lower. |
| Change From Baseline in Pulmonary Function Tests | Baseline, Month 60 | Pulmonary function was measured by sitting and supine % predicted forced vital capacity (FVC) |
| Change From Baseline in Muscle Strength Tests | Baseline, Month 60 | Muscle strength was measured by total manual muscle test (MMT) score. Total MMT score ranges from 0 to 80 based on all 16 muscle groups, which are right/left shoulder abduction, right/left shoulder adduction, right/left elbow flexion, right/left elbow extension, right/left hip flexion, right/left hip abduction, right/left knee flexion, and right/left knee extension. Higher scores indicate less disease impact on muscle functions. |
| Change From Baseline in Fatigue Severity Score (FSS) | Baseline, Month 60 | The Fatigue Severity Score (FSS) consists of 9 questions, each scored on a scale from 1 (completely disagree) to 7 (completely agree). The total score ranges from 9 to 63, with higher values representing higher level of fatigue due to the disease condition. |
Countries
Australia, Germany, Netherlands, New Zealand, United Kingdom, United States
Participant flow
Pre-assignment details
The study was conducted in 4 stages and 4 cohorts, with Stages 1 and 2 only for Cohort 1 and Stages 3 and 4 for all 4 cohorts.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 ERT-experienced ambulatory subjects with Pompe disease who had been on ERT for 2 to 6 years prior to enrollment and were able to walk at least 200 meters in the 6-minute walk test (6MWT) | 11 |
| Cohort 2 ERT-experienced non-ambulatory subjects with Pompe disease who had been on ERT for at least 2 years prior to enrollment | 6 |
| Cohort 3 ERT-naive ambulatory subjects with Pompe disease who were able to walk at least 200 meters in the 6MWT | 6 |
| Cohort 4 ERT-experienced ambulatory subjects with Pompe disease who had been on ERT for at least 7 years prior to enrollment and were able to walk at least 75 meters in the 6MWT | 6 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Stage 3: 2 Year Treatment | Adverse Event | 0 | 0 | 1 | 1 | 0 | 0 |
| Stage 3: 2 Year Treatment | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 |
| Stage 4: Long Term Extension | Death | 0 | 0 | 0 | 1 | 0 | 0 |
| Stage 4: Long Term Extension | Physician Decision | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 6 Participants | 5 Participants | 5 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 3 Participants | 1 Participants | 5 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 5 Participants | 1 Participants | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 5 Participants | 1 Participants | 12 Participants |
| Race (NIH/OMB) White | 8 Participants | 3 Participants | 1 Participants | 5 Participants | 17 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 5 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Male | 9 Participants | 4 Participants | 1 Participants | 2 Participants | 16 Participants |
| Years since diagnosis with Pompe disease | 7.7 years STANDARD_DEVIATION 5.11 | 15.9 years STANDARD_DEVIATION 13.08 | 5.2 years STANDARD_DEVIATION 4.7 | 13.0 years STANDARD_DEVIATION 4.3 | 10.0 years STANDARD_DEVIATION 7.98 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 1 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 7 / 11 | 5 / 11 | 4 / 11 | 9 / 11 | 11 / 11 | 6 / 6 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 7 / 11 | 4 / 6 | 4 / 6 | 6 / 6 |
Outcome results
Primary
Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events (AEs) Leading to Discontinuation of Study Drug
Number of subjects with TEAE, TESAE, and AE leading to discontinuation during the 2 year treatment period and extension (Stage 3 and 4 combined)
Time frame: Stage 3 (2 year treatment) and Stage 4 (Extension) combined, (mean = 71 months on treatment)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events (AEs) Leading to Discontinuation of Study Drug | Number of subjects with TEAEs | 11 Participants |
| Cohort 1 | Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events (AEs) Leading to Discontinuation of Study Drug | Number of subjects with AEs leading to discontinuation | 1 Participants |
| Cohort 1 | Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events (AEs) Leading to Discontinuation of Study Drug | Number of subjects with TESAEs | 7 Participants |
| Cohort 2 | Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events (AEs) Leading to Discontinuation of Study Drug | Number of subjects with TEAEs | 6 Participants |
| Cohort 2 | Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events (AEs) Leading to Discontinuation of Study Drug | Number of subjects with AEs leading to discontinuation | 2 Participants |
| Cohort 2 | Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events (AEs) Leading to Discontinuation of Study Drug | Number of subjects with TESAEs | 4 Participants |
| Cohort 3 | Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events (AEs) Leading to Discontinuation of Study Drug | Number of subjects with TESAEs | 4 Participants |
| Cohort 3 | Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events (AEs) Leading to Discontinuation of Study Drug | Number of subjects with TEAEs | 6 Participants |
| Cohort 3 | Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events (AEs) Leading to Discontinuation of Study Drug | Number of subjects with AEs leading to discontinuation | 0 Participants |
| Cohort 4 | Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events (AEs) Leading to Discontinuation of Study Drug | Number of subjects with TEAEs | 6 Participants |
| Cohort 4 | Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events (AEs) Leading to Discontinuation of Study Drug | Number of subjects with AEs leading to discontinuation | 0 Participants |
| Cohort 4 | Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events (AEs) Leading to Discontinuation of Study Drug | Number of subjects with TESAEs | 6 Participants |
Primary
Plasma GAA Activity Levels as Measured by Area Under the Plasma Drug Concentration-time Curve (AUC).
Plasma GAA levels (AUC) measured in Cohorts 1 and 3 following 1st and 3rd doses of cipaglucosidase alfa + miglustat
Time frame: 18 Weeks
Population: PK analysis only performed in Cohort 1 and Cohort 3. One subject each in Cohort 1 and Cohort 3 did not have PK sample available following first dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Plasma GAA Activity Levels as Measured by Area Under the Plasma Drug Concentration-time Curve (AUC). | Cipaglucosidase alfa 20 mg/kg + miglustat 260 mg (1st Dose) | 608180 nmol*hr/mL | Geometric Coefficient of Variation 23.7 |
| Cohort 1 | Plasma GAA Activity Levels as Measured by Area Under the Plasma Drug Concentration-time Curve (AUC). | Cipaglucosidase alfa 20 mg/kg + miglustat 260 mg (3rd Dose) | 670754 nmol*hr/mL | Geometric Coefficient of Variation 29.4 |
| Cohort 2 | Plasma GAA Activity Levels as Measured by Area Under the Plasma Drug Concentration-time Curve (AUC). | Cipaglucosidase alfa 20 mg/kg + miglustat 260 mg (1st Dose) | 762484 nmol*hr/mL | Geometric Coefficient of Variation 22 |
| Cohort 2 | Plasma GAA Activity Levels as Measured by Area Under the Plasma Drug Concentration-time Curve (AUC). | Cipaglucosidase alfa 20 mg/kg + miglustat 260 mg (3rd Dose) | 638984 nmol*hr/mL | Geometric Coefficient of Variation 18.1 |
Primary
Plasma GAA Activity Levels as Measured by Time to Reach the Maximum Observed Plasma Concentration (Tmax).
Plasma GAA levels (Tmax) measured in Cohorts 1 and 3 following 1st and 3rd doses of cipaglucosidase alfa + miglustat
Time frame: 18 Weeks
Population: PK analysis only performed in Cohort 1 and Cohort 3. One subject each in Cohort 1 and Cohort 3 did not have PK sample available following first dose.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 | Plasma GAA Activity Levels as Measured by Time to Reach the Maximum Observed Plasma Concentration (Tmax). | Cipaglucosidase alfa 20 mg/kg + miglustat 260 mg (1st Dose) | 3.49 h |
| Cohort 1 | Plasma GAA Activity Levels as Measured by Time to Reach the Maximum Observed Plasma Concentration (Tmax). | Cipaglucosidase alfa 20 mg/kg + miglustat 260 mg (3rd Dose) | 3.57 h |
| Cohort 2 | Plasma GAA Activity Levels as Measured by Time to Reach the Maximum Observed Plasma Concentration (Tmax). | Cipaglucosidase alfa 20 mg/kg + miglustat 260 mg (1st Dose) | 3.97 h |
| Cohort 2 | Plasma GAA Activity Levels as Measured by Time to Reach the Maximum Observed Plasma Concentration (Tmax). | Cipaglucosidase alfa 20 mg/kg + miglustat 260 mg (3rd Dose) | 3.66 h |
Primary
Plasma Human Acid α-glucosidase (GAA) Activity Levels as Measured by Maximum Observed Plasma Concentration (Cmax).
Plasma GAA levels (Cmax) measured in Cohorts 1 and 3 following 1st and 3rd doses of cipaglucosidase alfa + miglustat
Time frame: 18 Weeks
Population: Pharmacokinetic (PK) analysis only performed in Cohort 1 and Cohort 3. One subject each in Cohort 1 and Cohort 3 did not have PK sample available following first dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Plasma Human Acid α-glucosidase (GAA) Activity Levels as Measured by Maximum Observed Plasma Concentration (Cmax). | Cipaglucosidase alfa 20 mg/kg + miglustat 260 mg (1st dose) | 108836 nmol/mL/hr | Geometric Coefficient of Variation 20.5 |
| Cohort 1 | Plasma Human Acid α-glucosidase (GAA) Activity Levels as Measured by Maximum Observed Plasma Concentration (Cmax). | Cipaglucosidase alfa 20 mg/kg + miglustat 260 mg (3rd dose) | 119624 nmol/mL/hr | Geometric Coefficient of Variation 25.7 |
| Cohort 2 | Plasma Human Acid α-glucosidase (GAA) Activity Levels as Measured by Maximum Observed Plasma Concentration (Cmax). | Cipaglucosidase alfa 20 mg/kg + miglustat 260 mg (1st dose) | 132400 nmol/mL/hr | Geometric Coefficient of Variation 14.3 |
| Cohort 2 | Plasma Human Acid α-glucosidase (GAA) Activity Levels as Measured by Maximum Observed Plasma Concentration (Cmax). | Cipaglucosidase alfa 20 mg/kg + miglustat 260 mg (3rd dose) | 105842 nmol/mL/hr | Geometric Coefficient of Variation 15.4 |
Secondary
Change From Baseline in 6-minute Walk Distance (6MWD)
Motor function was measured in ambulatory subjects using 6MWD (meters).
Time frame: Baseline, Month 60
Population: Motor function was evaluated using the Efficacy Population (consisting of subjects who took at least 1 dose of study drug (20 mg/kg cipaglucosidase alfa + 260 mg miglustat) and had both a baseline and at least 1 post-baseline assessment for any efficacy endpoint. 6-minute walk distance (6MWD) was only performed in ambulatory subjects (Cohorts 1, 3, and 4). Baseline and Month 60 assessment available for 9 subjects in Cohort 1, 6 subjects in Cohort 3, and 4 subjects in Cohort 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Change From Baseline in 6-minute Walk Distance (6MWD) | 9.2 meters | Standard Deviation 49.89 |
| Cohort 2 | Change From Baseline in 6-minute Walk Distance (6MWD) | -34.9 meters | Standard Deviation 118.8 |
| Cohort 3 | Change From Baseline in 6-minute Walk Distance (6MWD) | 27.7 meters | Standard Deviation 74.5 |
Secondary
Change From Baseline in Fatigue Severity Score (FSS)
The Fatigue Severity Score (FSS) consists of 9 questions, each scored on a scale from 1 (completely disagree) to 7 (completely agree). The total score ranges from 9 to 63, with higher values representing higher level of fatigue due to the disease condition.
Time frame: Baseline, Month 60
Population: The Efficacy Population consists of all enrolled subjects who took at least 1 dose of study drug (20 mg/kg cipaglucosidase alfa + 260 mg miglustat co-administration) in Stage 3 and had both a baseline and at least 1 post-baseline assessment for any efficacy endpoint. Number of participants analyzed for FSS are those in each cohort who completed the assessment at baseline and Month 60.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Change From Baseline in Fatigue Severity Score (FSS) | 0.9 score on a scale | Standard Deviation 11.48 |
| Cohort 2 | Change From Baseline in Fatigue Severity Score (FSS) | -4.3 score on a scale | Standard Deviation 7.23 |
| Cohort 3 | Change From Baseline in Fatigue Severity Score (FSS) | -0.5 score on a scale | Standard Deviation 8.67 |
| Cohort 4 | Change From Baseline in Fatigue Severity Score (FSS) | -14.0 score on a scale | Standard Deviation 15.25 |
Secondary
Change From Baseline in Muscle Strength Tests
Muscle strength was measured by total manual muscle test (MMT) score. Total MMT score ranges from 0 to 80 based on all 16 muscle groups, which are right/left shoulder abduction, right/left shoulder adduction, right/left elbow flexion, right/left elbow extension, right/left hip flexion, right/left hip abduction, right/left knee flexion, and right/left knee extension. Higher scores indicate less disease impact on muscle functions.
Time frame: Baseline, Month 60
Population: Total MMT score was evaluated using the Efficacy Population consisting of all enrolled subjects who took at least 1 dose of study drug (20 mg/kg cipaglucosidase alfa + 260 mg miglustat co-administration) in Stage 3 and had both a baseline and at least 1 post-baseline assessment for any efficacy endpoint. Number of participants analyzed per cohort represents the number of subjects assessed at the specific visit for the parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Change From Baseline in Muscle Strength Tests | 2.0 score on a scale | Standard Deviation 5.2 |
| Cohort 2 | Change From Baseline in Muscle Strength Tests | 0.0 score on a scale | Standard Deviation 4.36 |
| Cohort 3 | Change From Baseline in Muscle Strength Tests | 1.0 score on a scale | Standard Deviation 3.54 |
| Cohort 4 | Change From Baseline in Muscle Strength Tests | 3.4 score on a scale | Standard Deviation 4.83 |
Secondary
Change From Baseline in Overall Physical Wellbeing (Physician's Global Impression of Change [PGIC])
The Physician's Global Impression of Change overall physical wellbeing is scored on a 7-point rating scale. Improved = response of 5 or higher, No change = response of 4, and Declined = response of 3 or lower.
Time frame: Baseline, Month 60
Population: Number of participants analyzed per cohort represents the number of subjects assessed at the specific visit for the parameter. Eight subjects in Cohort 1, 3 subjects in Cohort 2, and 5 subjects in Cohort 4 had PGIC values reported at Month 60.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Change From Baseline in Overall Physical Wellbeing (Physician's Global Impression of Change [PGIC]) | Improved | 2 Participants |
| Cohort 1 | Change From Baseline in Overall Physical Wellbeing (Physician's Global Impression of Change [PGIC]) | Declined | 3 Participants |
| Cohort 1 | Change From Baseline in Overall Physical Wellbeing (Physician's Global Impression of Change [PGIC]) | No change | 3 Participants |
| Cohort 2 | Change From Baseline in Overall Physical Wellbeing (Physician's Global Impression of Change [PGIC]) | Improved | 1 Participants |
| Cohort 2 | Change From Baseline in Overall Physical Wellbeing (Physician's Global Impression of Change [PGIC]) | Declined | 0 Participants |
| Cohort 2 | Change From Baseline in Overall Physical Wellbeing (Physician's Global Impression of Change [PGIC]) | No change | 2 Participants |
| Cohort 3 | Change From Baseline in Overall Physical Wellbeing (Physician's Global Impression of Change [PGIC]) | No change | 4 Participants |
| Cohort 3 | Change From Baseline in Overall Physical Wellbeing (Physician's Global Impression of Change [PGIC]) | Improved | 2 Participants |
| Cohort 3 | Change From Baseline in Overall Physical Wellbeing (Physician's Global Impression of Change [PGIC]) | Declined | 0 Participants |
| Cohort 4 | Change From Baseline in Overall Physical Wellbeing (Physician's Global Impression of Change [PGIC]) | Improved | 2 Participants |
| Cohort 4 | Change From Baseline in Overall Physical Wellbeing (Physician's Global Impression of Change [PGIC]) | Declined | 0 Participants |
| Cohort 4 | Change From Baseline in Overall Physical Wellbeing (Physician's Global Impression of Change [PGIC]) | No change | 3 Participants |
Secondary
Change From Baseline in Overall Physical Wellbeing (Subject's Global Impression of Change [SGIC], Question1)
The Subject's Global Impression of Change overall physical wellbeing (question 1) is scored on a 7-point rating scale. Improved = response of 5 or higher, No change = response of 4, and Declined = response of 3 or lower.
Time frame: Baseline, Month 60
Population: Number of participants analyzed per cohort represents the number of subjects assessed at the specific visit for the parameter. Eight subjects in Cohort 1, 2 subjects in Cohort 2, and 5 subjects in Cohort 4 had SGIC values reported at Month 60.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Change From Baseline in Overall Physical Wellbeing (Subject's Global Impression of Change [SGIC], Question1) | Declined | 3 Participants |
| Cohort 1 | Change From Baseline in Overall Physical Wellbeing (Subject's Global Impression of Change [SGIC], Question1) | No change | 2 Participants |
| Cohort 1 | Change From Baseline in Overall Physical Wellbeing (Subject's Global Impression of Change [SGIC], Question1) | Improved | 3 Participants |
| Cohort 2 | Change From Baseline in Overall Physical Wellbeing (Subject's Global Impression of Change [SGIC], Question1) | Declined | 0 Participants |
| Cohort 2 | Change From Baseline in Overall Physical Wellbeing (Subject's Global Impression of Change [SGIC], Question1) | Improved | 0 Participants |
| Cohort 2 | Change From Baseline in Overall Physical Wellbeing (Subject's Global Impression of Change [SGIC], Question1) | No change | 2 Participants |
| Cohort 3 | Change From Baseline in Overall Physical Wellbeing (Subject's Global Impression of Change [SGIC], Question1) | Improved | 3 Participants |
| Cohort 3 | Change From Baseline in Overall Physical Wellbeing (Subject's Global Impression of Change [SGIC], Question1) | Declined | 2 Participants |
| Cohort 3 | Change From Baseline in Overall Physical Wellbeing (Subject's Global Impression of Change [SGIC], Question1) | No change | 1 Participants |
| Cohort 4 | Change From Baseline in Overall Physical Wellbeing (Subject's Global Impression of Change [SGIC], Question1) | No change | 0 Participants |
| Cohort 4 | Change From Baseline in Overall Physical Wellbeing (Subject's Global Impression of Change [SGIC], Question1) | Declined | 1 Participants |
| Cohort 4 | Change From Baseline in Overall Physical Wellbeing (Subject's Global Impression of Change [SGIC], Question1) | Improved | 4 Participants |
Secondary
Change From Baseline in Pulmonary Function Tests
Pulmonary function was measured by sitting and supine % predicted forced vital capacity (FVC)
Time frame: Baseline, Month 60
Population: Number of participants analyzed per cohort represents the number of subjects assessed at the specific visit for the parameter. Eight subjects in Cohort 1, 1 subject in Cohort 2, and 5 subjects in Cohort 4 had FVC values reported at Month 60.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Change From Baseline in Pulmonary Function Tests | Sitting % predicted FVC: Change from Baseline to Month 60 | -2.8 percent predicted FVC | Standard Deviation 10.93 |
| Cohort 1 | Change From Baseline in Pulmonary Function Tests | Supine % predicted FVC: Change from Baseline to Month 60 | 0.8 percent predicted FVC | Standard Deviation 7.59 |
| Cohort 2 | Change From Baseline in Pulmonary Function Tests | Supine % predicted FVC: Change from Baseline to Month 60 | -1.0 percent predicted FVC | Standard Deviation 0 |
| Cohort 2 | Change From Baseline in Pulmonary Function Tests | Sitting % predicted FVC: Change from Baseline to Month 60 | -8.0 percent predicted FVC | Standard Deviation 0 |
| Cohort 3 | Change From Baseline in Pulmonary Function Tests | Sitting % predicted FVC: Change from Baseline to Month 60 | 5.0 percent predicted FVC | Standard Deviation 8.07 |
| Cohort 3 | Change From Baseline in Pulmonary Function Tests | Supine % predicted FVC: Change from Baseline to Month 60 | 1.2 percent predicted FVC | Standard Deviation 9.34 |
| Cohort 4 | Change From Baseline in Pulmonary Function Tests | Sitting % predicted FVC: Change from Baseline to Month 60 | 3.8 percent predicted FVC | Standard Deviation 3.27 |
| Cohort 4 | Change From Baseline in Pulmonary Function Tests | Supine % predicted FVC: Change from Baseline to Month 60 | 5.5 percent predicted FVC | Standard Deviation 5.8 |