Sarcopenia
Conditions
Keywords
Sarcopenia, muscle wasting, elderly, strength, physical function, lean body mass, gait speed
Brief summary
This extension study was a 24-week off-drug follow-up of the core CBYM338E2202 (NCT ) study and the main objective was to determine the long-term durability of bimagrumab (BYM338) effect after a 6-month treatment period.
Detailed description
Two populations were defined as below: * Population I: Patients enrolled prior to the protocol amendment 1, who received bimagrumab 70 mg, 210 mg or 700 mg in the core study, were randomly assigned to two subgroups within each of three treatment arms to either receive bimagrumab at the same dose level or placebo. Patients receiving placebo in the core study continued receiving placebo in the extension study. * Population II: Patients enrolled after protocol amendment 1, who received bimagrumab 700 mg or placebo in the core study, did not receive study medication in the extension study and were followed-up per schedule defined in this protocol amendment.
Interventions
DRUGbimagrumab
bimagrumab low dose bimagrumab moderate dose bimagrumab high dose Patients enrolled prior to the protocol amendment 1 (Population I ), who received bimagrumab in the core study, entered the extension study at Week 25 and were randomly assigned to two subgroups within each of three treatment arms to either receive bimagrumab at the same dose level or placebo. Study medication was administered as an intravenous infusion starting at Week 25 after treatment was initiated in the core study until week 45.
DRUGPlacebo
Placebo Patients enrolled prior to the protocol amendment 1 (Population I), who received placebo in core study, entered the extension study at Week 25 and received placebo as an intravenous infusion starting at Week 25 after treatment was initiated in the core study until week 45.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion criterion: \- Men and postmenopausal women aged 70 years or older that have participated in, and have completed the full study treatment period per protocol (24 weeks/EOT visit) in the preceding core study (CBYM338E2202) Exclusion criterion: \- Any condition which should have led to treatment discontinuation per protocol in the core study (CBYM338E2202)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Population I: Short Physical Performance Battery (SPPB) Total Score at Week 49 | Week 49 | SPPB evaluates lower extremities in three functional components: maintenance of standing balance, usual gait speed and chair stand. Each test yields a score on a scale from 0 to 4 (total score 0-12, with the higher score reflecting a higher level of function). |
| Population II: Short Physical Performance Battery (SPPB) Total Score at Week 49 | Week 49 | SPPB evaluates lower extremities in three functional components: maintenance of standing balance, usual gait speed and chair stand. Each test yields a score on a scale from 0 to 4 (total score 0-12, with the higher score reflecting a higher level of function). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Population I: Gait Speed at Week 49 | Week 49 | Gait Speed was assessed as part of SPPB, over a 4 meter distance of a 6 meter course. Gait speed assesses a person's usual walking speed, which is defined as the speed a person normally walks from one place to another. Poor functional performance is measured by slow or declining gait speed. |
| Population II: Gait Speed at Week 49 | Week 49 | Gait Speed was assessed as part of SPPB, over a 4 meter distance of a 6 meter course. Gait speed assesses a person's usual walking speed, which is defined as the speed a person normally walks from one place to another. Poor functional performance is measured by slow or declining gait speed. |
| Population I: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | Week 49 | ASMI is a core requirement for determining the presence of sarcopenia and is calculated as the sum of the appendicular lean mass (kg) of the two upper and two lower limbs quantified by DXA, divided by height (m2). Therefore, an increase in ASMI indicates an increase in the quantity of an individual's lean mass. |
| Population I: 6-minute Walking Distance (6MWT) at Week 49 | Week 49 | The 6MWT measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is able to self-pace and rest as needed as they traverse back and forth along a marked walkway. A high 6MWT represent better physical condition. |
| Population I: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | Week 49 | LBM is defined as the Total soft tissue fat-free body mass. A high LBM represents better pharmacodynamic effect |
| Population II: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | Week 49 | LBM is defined as the Total soft tissue fat-free body mass. A high LBM represents better pharmacodynamic effect |
| Population II: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | Week 49 | ASMI is a core requirement for determining the presence of sarcopenia and is calculated as the sum of the appendicular lean mass (kg) of the two upper and two lower limbs quantified by DXA, divided by height (m2). Therefore, an increase in ASMI indicates an increase in the quantity of an individual's lean mass. |
| Population II: 6-minute Walking Distance (6MWT) at Week 49 | Week 49 | The 6MWT measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is able to self-pace and rest as needed as they traverse back and forth along a marked walkway. A high 6MWT represent better physical condition. |
Countries
Australia, Belgium, Czechia, Denmark, France, Japan, Russia, South Korea, Spain, Switzerland, Taiwan, United States
Participant flow
Recruitment details
This study was conducted in 30 centers in 12 countries: Australia (1), Belgium (1), Czech Republic (1), Denmark (1), France (2), Japan (10), Russia (4), South Korea (1), Spain (2), Switzerland (1), Taiwan (1), United States (5).
Participants by arm
| Arm | Count |
|---|---|
| Population I: BYM338 700 mg Follow-up (arm 1): Patients in Population I received 6 doses of bimagrumab 70 mg, 210 mg, 700 mg or placebo - one approximately every four weeks - over a 20-week period providing drug exposure for a total of 24 weeks. | 5 |
| Population I BYM338: 700 mg to Placebo Follow-up (arm 1): Patients in Population I received 6 doses of bimagrumab 70 mg, 210 mg, 700 mg or placebo - one approximately every four weeks - over a 20-week period providing drug exposure for a total of 24 weeks. | 5 |
| Population I: BYM338 210 mg Follow-up (arm 1): Patients in Population I received 6 doses of bimagrumab 70 mg, 210 mg, 700 mg or placebo - one approximately every four weeks - over a 20-week period providing drug exposure for a total of 24 weeks. | 5 |
| Population I BYM338: 210 mg to Placebo Follow-up (arm 1): Patients in Population I received 6 doses of bimagrumab 70 mg, 210 mg, 700 mg or placebo - one approximately every four weeks - over a 20-week period providing drug exposure for a total of 24 weeks. | 4 |
| Population I: BYM338 70 mg Follow-up (arm 1): Patients in Population I received 6 doses of bimagrumab 70 mg, 210 mg, 700 mg or placebo - one approximately every four weeks - over a 20-week period providing drug exposure for a total of 24 weeks. | 7 |
| Population I: BYM338 70 mg to Placebo Follow-up (arm 1): Patients in Population I received 6 doses of bimagrumab 70 mg, 210 mg, 700 mg or placebo - one approximately every four weeks - over a 20-week period providing drug exposure for a total of 24 weeks. | 7 |
| Population I: Placebo Follow-up (arm 1): Patients in Population I received 6 doses of bimagrumab 70 mg, 210 mg, 700 mg or placebo - one approximately every four weeks - over a 20-week period providing drug exposure for a total of 24 weeks. | 15 |
| Population: II BYM338 700 mg Follow-up (arm 2): Patients in Population II received either bimagrumab 700 mg or placebo in the core study and did not receive any investigational treatment in the extension study. | 69 |
| Population: II Placebo Follow-up (arm 2): Patients in Population II received either bimagrumab 700 mg or placebo in the core study and did not receive any investigational treatment in the extension study. | 43 |
| Total | 160 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Patient/Guardian Decision | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Deviation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Population I BYM338: 700 mg to Placebo | Population I: BYM338 700 mg | Population I: BYM338 210 mg | Population I BYM338: 210 mg to Placebo | Population I: BYM338 70 mg | Population I: BYM338 70 mg to Placebo | Population I: Placebo | Total | Population: II BYM338 700 mg | Population: II Placebo |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 79.4 Years STANDARD_DEVIATION 7.27 | 80.0 Years STANDARD_DEVIATION 4.9 | 79.0 Years STANDARD_DEVIATION 1.58 | 74.8 Years STANDARD_DEVIATION 2.63 | 77.6 Years STANDARD_DEVIATION 6.75 | 81.6 Years STANDARD_DEVIATION 4.58 | 79.9 Years STANDARD_DEVIATION 4.22 | 79.2 Years STANDARD_DEVIATION 5.18 | 79.8 Years STANDARD_DEVIATION 5.05 | 78.2 Years STANDARD_DEVIATION 5.29 |
| Population I: 6-minute walking distance (6MWT) at Week 25 | 353.10 meters STANDARD_DEVIATION 66.17 | 302.73 meters STANDARD_DEVIATION 130.22 | 313.67 meters STANDARD_DEVIATION 71.39 | 361.07 meters STANDARD_DEVIATION 80.11 | 305.24 meters STANDARD_DEVIATION 111.34 | 286.94 meters STANDARD_DEVIATION 119.37 | 352.18 meters STANDARD_DEVIATION 123.55 | 327.49 meters STANDARD_DEVIATION 106.64 | — | — |
| Population I: Gait speed at Week 25 | 0.9 m/sec STANDARD_DEVIATION 0.13 | 0.8 m/sec STANDARD_DEVIATION 0.2 | 0.9 m/sec STANDARD_DEVIATION 0.27 | 0.9 m/sec STANDARD_DEVIATION 0.12 | 0.8 m/sec STANDARD_DEVIATION 0.19 | 0.6 m/sec STANDARD_DEVIATION 0.28 | 0.8 m/sec STANDARD_DEVIATION 0.19 | 0.8 m/sec STANDARD_DEVIATION 0.21 | — | — |
| Population II: 6-minute walking distance (6MWT) at Week 25 | — | — | — | — | — | — | — | 310.81 meters STANDARD_DEVIATION 98.01 | 307.84 meters STANDARD_DEVIATION 99.96 | 315.61 meters STANDARD_DEVIATION 95.74 |
| Population II: Gait speed at Week 25 | — | — | — | — | — | — | — | 0.8 m/sec STANDARD_DEVIATION 0.22 | 0.8 m/sec STANDARD_DEVIATION 0.23 | 0.8 m/sec STANDARD_DEVIATION 0.22 |
| Population II: Short Physical Performance Battery (SPPB) total score at Week 25 | — | — | — | — | — | — | — | 8.4 Scores on a scale STANDARD_DEVIATION 2.2 | 8.5 Scores on a scale STANDARD_DEVIATION 2.17 | 8.2 Scores on a scale STANDARD_DEVIATION 2.25 |
| Population I: Short Physical Performance Battery (SPPB) total score at Week 25 | 10.4 Scores on a scale STANDARD_DEVIATION 1.34 | 8.8 Scores on a scale STANDARD_DEVIATION 2.17 | 8.6 Scores on a scale STANDARD_DEVIATION 1.67 | 8.5 Scores on a scale STANDARD_DEVIATION 1.91 | 8.9 Scores on a scale STANDARD_DEVIATION 2.04 | 8.0 Scores on a scale STANDARD_DEVIATION 3.27 | 9.1 Scores on a scale STANDARD_DEVIATION 1.58 | 8.9 Scores on a scale STANDARD_DEVIATION 2.01 | — | — |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 6 Participants | 12 Participants | 11 Participants | 3 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | — | — |
| Race/Ethnicity, Customized Caucasian | 5 Participants | 4 Participants | 5 Participants | 3 Participants | 4 Participants | 4 Participants | 8 Participants | 96 Participants | 56 Participants | 40 Participants |
| Race/Ethnicity, Customized Native American | — | — | — | — | — | — | — | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Pacific Islander | — | — | — | — | — | — | — | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 5 Participants | 8 Participants | 23 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 3 Participants | 2 Participants | 4 Participants | 2 Participants | 0 Participants | 43 Participants | 29 Participants | 14 Participants |
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 | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 4 | 0 / 7 | 0 / 7 | 0 / 15 | 0 / 69 | 0 / 43 |
| other Total, other adverse events | 4 / 5 | 4 / 5 | 3 / 5 | 2 / 4 | 5 / 7 | 3 / 7 | 11 / 15 | 0 / 69 | 0 / 43 |
| serious Total, serious adverse events | 0 / 5 | 1 / 5 | 0 / 5 | 0 / 4 | 0 / 7 | 2 / 7 | 2 / 15 | 0 / 69 | 0 / 43 |
Outcome results
Primary
Population II: Short Physical Performance Battery (SPPB) Total Score at Week 49
SPPB evaluates lower extremities in three functional components: maintenance of standing balance, usual gait speed and chair stand. Each test yields a score on a scale from 0 to 4 (total score 0-12, with the higher score reflecting a higher level of function).
Time frame: Week 49
Population: The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered. For post Week 25 assessments, only the subjects with assessment available at both the Visit and Week 25 are included in the calculation of the respective Visit statistics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Population I: BYM338 700 mg | Population II: Short Physical Performance Battery (SPPB) Total Score at Week 49 | 8.6 Scores on a scale | Standard Deviation 2.4 |
| Population I BYM338: 700 mg to Placebo | Population II: Short Physical Performance Battery (SPPB) Total Score at Week 49 | 8.8 Scores on a scale | Standard Deviation 1.55 |
Comparison: Population II: SPPB total score at Week 49p-value: 0.839ANCOVA
Primary
Population I: Short Physical Performance Battery (SPPB) Total Score at Week 49
SPPB evaluates lower extremities in three functional components: maintenance of standing balance, usual gait speed and chair stand. Each test yields a score on a scale from 0 to 4 (total score 0-12, with the higher score reflecting a higher level of function).
Time frame: Week 49
Population: The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered. For post Week 25 assessments, only the subjects with assessment available at both the Visit and Week 25 are included in the calculation of the respective Visit statistics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Population I: BYM338 700 mg | Population I: Short Physical Performance Battery (SPPB) Total Score at Week 49 | 8.8 Scores on a scale | Standard Deviation 3.86 |
| Population I BYM338: 700 mg to Placebo | Population I: Short Physical Performance Battery (SPPB) Total Score at Week 49 | 10.2 Scores on a scale | Standard Deviation 1.92 |
| Population I: BYM338 210 mg | Population I: Short Physical Performance Battery (SPPB) Total Score at Week 49 | 8.0 Scores on a scale | Standard Deviation 2.35 |
| Population I BYM338: 210 mg to Placebo | Population I: Short Physical Performance Battery (SPPB) Total Score at Week 49 | 8.0 Scores on a scale | Standard Deviation 2.65 |
| Population I: BYM338 70 mg | Population I: Short Physical Performance Battery (SPPB) Total Score at Week 49 | 9.5 Scores on a scale | Standard Deviation 2.17 |
| Population I: BYM338 70 mg to Placebo | Population I: Short Physical Performance Battery (SPPB) Total Score at Week 49 | 7.5 Scores on a scale | Standard Deviation 3.78 |
| Population I: Placebo | Population I: Short Physical Performance Battery (SPPB) Total Score at Week 49 | 9.6 Scores on a scale | Standard Deviation 1.83 |
Comparison: Population I: SPPB total score at Week 49p-value: 0.759t-test, 1 sided
Comparison: Population I: SPPB total score at Week 49p-value: 0.5t-test, 1 sided
Comparison: Population I: SPPB total score at Week 49p-value: 0.144t-test, 1 sided
Comparison: Population I: SPPB total score at Week 49p-value: 0.648t-test, 1 sided
Comparison: Population I: SPPB total score at Week 49p-value: 0.929t-test, 1 sided
Comparison: Population I: SPPB total score at Week 49p-value: 0.53t-test, 1 sided
Secondary
Population I: 6-minute Walking Distance (6MWT) at Week 49
The 6MWT measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is able to self-pace and rest as needed as they traverse back and forth along a marked walkway. A high 6MWT represent better physical condition.
Time frame: Week 49
Population: The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered. For post Week 25 assessments, only the subjects with assessment available at both the Visit and Week 25 are included in the calculation of the respective Visit statistics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Population I: BYM338 700 mg | Population I: 6-minute Walking Distance (6MWT) at Week 49 | 318.2 meters | Standard Deviation 159.55 |
| Population I BYM338: 700 mg to Placebo | Population I: 6-minute Walking Distance (6MWT) at Week 49 | 354.1 meters | Standard Deviation 69.98 |
| Population I: BYM338 210 mg | Population I: 6-minute Walking Distance (6MWT) at Week 49 | 304.1 meters | Standard Deviation 63.05 |
| Population I BYM338: 210 mg to Placebo | Population I: 6-minute Walking Distance (6MWT) at Week 49 | 361.5 meters | Standard Deviation 144.53 |
| Population I: BYM338 70 mg | Population I: 6-minute Walking Distance (6MWT) at Week 49 | 316.1 meters | Standard Deviation 97.87 |
| Population I: BYM338 70 mg to Placebo | Population I: 6-minute Walking Distance (6MWT) at Week 49 | 273.4 meters | Standard Deviation 154.03 |
| Population I: Placebo | Population I: 6-minute Walking Distance (6MWT) at Week 49 | 368.7 meters | Standard Deviation 108.37 |
Comparison: Population I: 6MWT at Week 49p-value: 0.669t-test, 1 sided
Comparison: Population I: 6MWT at Week 49p-value: 0.773t-test, 1 sided
Comparison: Population I: 6MWT at Week 49p-value: 0.29t-test, 1 sided
Comparison: Population I: 6MWT at Week 49p-value: 0.766t-test, 1 sided
Comparison: Population I: 6MWT at Week 49p-value: 0.885t-test, 1 sided
Comparison: Population I: 6MWT at Week 49p-value: 0.84t-test, 1 sided
Secondary
Population I: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49
ASMI is a core requirement for determining the presence of sarcopenia and is calculated as the sum of the appendicular lean mass (kg) of the two upper and two lower limbs quantified by DXA, divided by height (m2). Therefore, an increase in ASMI indicates an increase in the quantity of an individual's lean mass.
Time frame: Week 49
Population: The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered. For post Week 25 assessments, only the subjects with assessment available at both the Visit and Week 25 are included in the calculation of the respective Visit statistics.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Population I: BYM338 700 mg | Population I: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 6.6 kg/m^2 | Geometric Coefficient of Variation 7.22 |
| Population I BYM338: 700 mg to Placebo | Population I: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 6.0 kg/m^2 | Geometric Coefficient of Variation 14.05 |
| Population I: BYM338 210 mg | Population I: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 6.1 kg/m^2 | Geometric Coefficient of Variation 8.08 |
| Population I BYM338: 210 mg to Placebo | Population I: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 5.8 kg/m^2 | Geometric Coefficient of Variation 15.08 |
| Population I: BYM338 70 mg | Population I: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 5.9 kg/m^2 | Geometric Coefficient of Variation 14.19 |
| Population I: BYM338 70 mg to Placebo | Population I: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 5.2 kg/m^2 | Geometric Coefficient of Variation 14.85 |
| Population I: Placebo | Population I: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 5.6 kg/m^2 | Geometric Coefficient of Variation 15.21 |
Comparison: Population I: ASMI at Week 49p-value: 0.12t-test, 1 sided
Comparison: Population I: ASMI at Week 49p-value: 0.297t-test, 1 sided
Comparison: Population I: ASMI at Week 49p-value: 0.074t-test, 1 sided
Comparison: Population I: ASMI at Week 49p-value: 0.022t-test, 1 sided
Comparison: Population I: ASMI at Week 49p-value: 0.106t-test, 1 sided
Comparison: Population I: ASMI at Week 49p-value: 0.211t-test, 1 sided
Secondary
Population I: Gait Speed at Week 49
Gait Speed was assessed as part of SPPB, over a 4 meter distance of a 6 meter course. Gait speed assesses a person's usual walking speed, which is defined as the speed a person normally walks from one place to another. Poor functional performance is measured by slow or declining gait speed.
Time frame: Week 49
Population: The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered. For post Week 25 assessments, only the subjects with assessment available at both the Visit and Week 25 are included in the calculation of the respective Visit statistics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Population I: BYM338 700 mg | Population I: Gait Speed at Week 49 | 0.8 m/sec | Standard Deviation 0.35 |
| Population I BYM338: 700 mg to Placebo | Population I: Gait Speed at Week 49 | 1.0 m/sec | Standard Deviation 0.18 |
| Population I: BYM338 210 mg | Population I: Gait Speed at Week 49 | 0.9 m/sec | Standard Deviation 0.17 |
| Population I BYM338: 210 mg to Placebo | Population I: Gait Speed at Week 49 | 1.1 m/sec | Standard Deviation 0.24 |
| Population I: BYM338 70 mg | Population I: Gait Speed at Week 49 | 0.9 m/sec | Standard Deviation 0.15 |
| Population I: BYM338 70 mg to Placebo | Population I: Gait Speed at Week 49 | 0.7 m/sec | Standard Deviation 0.35 |
| Population I: Placebo | Population I: Gait Speed at Week 49 | 0.8 m/sec | Standard Deviation 0.18 |
Comparison: Population I: Gait speed at Week 49p-value: 0.875t-test, 1 sided
Comparison: Population I: Gait speed at Week 49p-value: 0.909t-test, 1 sided
Comparison: Population I: Gait speed at Week 49p-value: 0.168t-test, 1 sided
Comparison: Population I: Gait speed at Week 49p-value: 0.632t-test, 1 sided
Comparison: Population I: Gait speed at Week 49p-value: 0.31t-test, 1 sided
Comparison: Population I: Gait speed at Week 49p-value: 0.321t-test, 1 sided
Secondary
Population II: 6-minute Walking Distance (6MWT) at Week 49
The 6MWT measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is able to self-pace and rest as needed as they traverse back and forth along a marked walkway. A high 6MWT represent better physical condition.
Time frame: Week 49
Population: The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered. For post Week 25 assessments, only the subjects with assessment available at both the Visit and Week 25 are included in the calculation of the respective Visit statistics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Population I: BYM338 700 mg | Population II: 6-minute Walking Distance (6MWT) at Week 49 | 321.2 meters | Standard Deviation 105.13 |
| Population I BYM338: 700 mg to Placebo | Population II: 6-minute Walking Distance (6MWT) at Week 49 | 323.1 meters | Standard Deviation 96.47 |
Comparison: Population II: 6MWT at Week 49p-value: 0.367ANCOVA
Secondary
Population II: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49
ASMI is a core requirement for determining the presence of sarcopenia and is calculated as the sum of the appendicular lean mass (kg) of the two upper and two lower limbs quantified by DXA, divided by height (m2). Therefore, an increase in ASMI indicates an increase in the quantity of an individual's lean mass.
Time frame: Week 49
Population: The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered. For post Week 25 assessments, only the subjects with assessment available at both the Visit and Week 25 are included in the calculation of the respective Visit statistics.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Population I: BYM338 700 mg | Population II: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 5.6 kg/m^2 | Geometric Coefficient of Variation 14.36 |
| Population I BYM338: 700 mg to Placebo | Population II: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 5.5 kg/m^2 | Geometric Coefficient of Variation 12.46 |
Comparison: Population II: ASMI at Week 49p-value: 1ANCOVA
Secondary
Population II: Gait Speed at Week 49
Gait Speed was assessed as part of SPPB, over a 4 meter distance of a 6 meter course. Gait speed assesses a person's usual walking speed, which is defined as the speed a person normally walks from one place to another. Poor functional performance is measured by slow or declining gait speed.
Time frame: Week 49
Population: The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered. For post Week 25 assessments, only the subjects with assessment available at both the Visit and Week 25 are included in the calculation of the respective Visit statistics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Population I: BYM338 700 mg | Population II: Gait Speed at Week 49 | 0.9 m/sec | Standard Deviation 0.24 |
| Population I BYM338: 700 mg to Placebo | Population II: Gait Speed at Week 49 | 0.9 m/sec | Standard Deviation 0.17 |
Comparison: Population II: Gait speed at Week 49p-value: 0.395ANCOVA
Secondary
Population II: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49
LBM is defined as the Total soft tissue fat-free body mass. A high LBM represents better pharmacodynamic effect
Time frame: Week 49
Population: The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered. For post Week 25 assessments, only the subjects with assessment available at both the Visit and Week 25 are included in the calculation of the respective Visit statistics.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Population I: BYM338 700 mg | Population II: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 34.9 kg | Geometric Coefficient of Variation 25.01 |
| Population I BYM338: 700 mg to Placebo | Population II: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 33.7 kg | Geometric Coefficient of Variation 20.4 |
Comparison: Population II: LBM at Week 49p-value: 1ANCOVA
Secondary
Population I: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49
LBM is defined as the Total soft tissue fat-free body mass. A high LBM represents better pharmacodynamic effect
Time frame: Week 49
Population: The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered. For post Week 25 assessments, only the subjects with assessment available at both the Visit and Week 25 are included in the calculation of the respective Visit statistics.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Population I: BYM338 700 mg | Population I: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 41.4 kg | Geometric Coefficient of Variation 21.11 |
| Population I BYM338: 700 mg to Placebo | Population I: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 34.0 kg | Geometric Coefficient of Variation 17.76 |
| Population I: BYM338 210 mg | Population I: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 35.5 kg | Geometric Coefficient of Variation 15.39 |
| Population I BYM338: 210 mg to Placebo | Population I: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 32.6 kg | Geometric Coefficient of Variation 25.23 |
| Population I: BYM338 70 mg | Population I: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 34.9 kg | Geometric Coefficient of Variation 21.16 |
| Population I: BYM338 70 mg to Placebo | Population I: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 34.0 kg | Geometric Coefficient of Variation 18.47 |
| Population I: Placebo | Population I: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 32.6 kg | Geometric Coefficient of Variation 17.95 |
Comparison: Population I: LBM at Week 49p-value: 0.084t-test, 1 sided
Comparison: Population I: LBM at Week 49p-value: 0.283t-test, 1 sided
Comparison: Population I: LBM at Week 49p-value: 0.323t-test, 1 sided
Comparison: Population I: LBM at Week 49p-value: 0.018t-test, 1 sided
Comparison: Population I: LBM at Week 49p-value: 0.179t-test, 1 sided
Comparison: Population I: LBM at Week 49p-value: 0.227t-test, 1 sided