Sarcopenia
Conditions
Keywords
Sarcopenia, muscle wasting, elderly, strength, physical function, muscle, gait speed
Brief summary
The purpose of this study was to determine the efficacy of repeat dosing with multiple dose levels of bimagrumab on patient physical function, skeletal muscle mass and strength in older adults with sarcopenia. In addition, this study generated data on the safety, tolerability, and pharmacokinetics of bimagrumab in older adults with sarcopenia.
Interventions
DRUGbimagrumab
Bimagrumab will be administered as an intravenous infusion starting on Day 1 until week 21.
OTHERplacebo
Placebo will be administered as an intravenous infusion starting on Day 1 until week 21.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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
* Low muscle mass as confirmed by DXA; * Low gait speed \<0.8 m/s * SPPB score less than or equal to 9; * Weigh at least 35 kg; * Adequate dietary intake;
Exclusion criteria
* A lower limb fracture in the past 6 months or any impairment or disease severely affecting gait (e.g. stroke with hemiparesis, myasthenia gravis, Parkinson's disease, peripheral polyneuropathy, intermittent claudication in advanced peripheral vascular disease, spinal stenosis, or severe osteoarthritis of the knee or hip with ineffective pain management); * Requires regular assistance from another person for general activities of daily living (e.g. bathing, dressing, toileting). * Intraocular surgery and laser procedures for refractive correction within 6 months prior to screening; * Any underlying muscle disease including active myopathy or muscular dytrophy; * Confirmed diagnosis of heart failure classified as New York Heart Association Class III or IV (e.g. dilated cardiomyopathy); * Type I diabetes or uncontrolled Type 2 diabetes; * Chronic kidney disease \[estimated glomerular filtration rate (GFR) \< 30 mL/min\]; * History of confirmed chronic obstructive pulmonary disease with a severity grade \> 2 on the Medical Research Council Dyspnea Scale; * Confirmed rheumatoid arthritis or other systemic autoimmune disease requiring immunosuppressive therapy or corticosteroids \>10 mg/d prednisone equivalent; * Known history or presence of severe active acute or chronic liver disease (e.g., cirrhosis); * Myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention (e.g. angioplasty or stent placement), or deep vein thrombosis/pulmonary embolism within 12 weeks of screening; * Active cancer (i.e., under current treatment), or cancer requiring treatment in the last 5 years excluding non-melanoma skin cancers or cancers with excellent prognosis (e.g., early stage prostate or breast cancer, carcinoma in situ of the uterine cervix); * Any chronic active infection (e.g., HIV, Hepatitis B or C, tuberculosis, etc).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Short Physical Performance Battery (SPPB) Score to Week 25 | Baseline, week 25 | Change from Baseline in total Short Physical Performance Battery (SPPB) Score to week 25; SPPB is a series of six activities involving three domains of physical function - balance, usual walking speed and rising from a chair , is commonly used globally to assess and quantify (score 0-12) lower extremity function and has been shown to predict future adverse health events. A decline of one or more points in the SPPB total score is predictive of a decrease in lower extremity function and future adverse clinical outcomes in older adults, including falls, hospitalizations, institutionalization, incident disability and death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Week 25 in the 6 Minute Walk Test (6MWT) Distance | Baseline, week 25 | Change from Baseline at Week 25 in the 6 minute walk test (6MWT) distance to measure improvement in physical function |
| Change From Baseline to Week 25 in Usual Gait Speed (GS) Over 4 Meters | baseline, week 25 | Change from Baseline to Week 25 in usual Gait speed (GS) over 4 meters Gait speed in this study was assessed as part of the SPPB, over a 4 meter distance of a 6 meter course. This test assessed a person's usual walking speed, which was defined as the speed a person normally walks from one place to another without urgency (e.g., walking down a hallway). |
| Percentage Change From Baseline to Week 25 on Appendicular Skeletal Muscle Index (ASMI) Measured by Dual Energy X-ray Absorptiometry (DXA) | baseline, week 25 | Change from Baseline to Week 25 on appendicular skeletal muscle index (ASMI) measured by Dual Energy X-ray Absorptiometry (DXA) Appendicular skeletal muscle index (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 (m\^2). Therefore, an increase in ASMI indicates an increase in the quantity of an individual's lean mass. |
| Percentage Change From Baseline to Week 25 on Total Lean Body Mass Measured by Dual Energy X-ray Absorptiometry (DXA) | baseline, week 25 | Change from Baseline to Week 25 on Total lean body mass and appendicular skeletal muscle index (ASMI) measured by Dual Energy X-ray Absorptiometry (DXA) total lean body mass (LBM) is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(LBM at Visit - LBM at Baseline) / LBM at Baseline\] \* 100. |
Countries
Australia, Belgium, Czechia, Denmark, France, Germany, Japan, Russia, South Korea, Spain, Switzerland, Taiwan, United States
Participant flow
Recruitment details
A total of 220 patients were randomized to receive six doses of either BYM338 70 mg, BYM338 210 mg, BYM338 700 mg or the placebo. However, only 217 patients were enrolled and dosed with BYM338 or placebo due to the withdrawal of three patients who did not meet the inclusion/exclusion criteria prior to receiving the first dose.
Participants by arm
| Arm | Count |
|---|---|
| BYM338 70 mg BYM338 70 mg intravenous infusion | 19 |
| BYM338 210 mg BYM338 210 mg intravenous infusion | 18 |
| BYM338 700 mg BYM338 700 mg intravenous infusion | 113 |
| Placebo Placebo intravenous infusion | 67 |
| Total | 217 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 4 | 1 |
| Overall Study | Death | 0 | 0 | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Overall Study | Patient/Guardian Decision | 1 | 2 | 9 | 1 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Deviation | 0 | 3 | 2 | 1 |
Baseline characteristics
| Characteristic | BYM338 70 mg | Total | Placebo | BYM338 700 mg | BYM338 210 mg |
|---|---|---|---|---|---|
| Age, Continuous | 79.3 years STANDARD_DEVIATION 5.89 | 79.0 years STANDARD_DEVIATION 5.45 | 78.3 years STANDARD_DEVIATION 5.03 | 79.5 years STANDARD_DEVIATION 5.46 | 78.0 years STANDARD_DEVIATION 6.38 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 36 Participants | 11 Participants | 17 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 11 Participants | 172 Participants | 54 Participants | 93 Participants | 14 Participants |
| Sex: Female, Male Female | 9 Participants | 126 Participants | 43 Participants | 66 Participants | 8 Participants |
| Sex: Female, Male Male | 10 Participants | 91 Participants | 24 Participants | 47 Participants | 10 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 / 19 | 0 / 18 | 2 / 113 | 0 / 67 |
| other Total, other adverse events | 12 / 19 | 13 / 18 | 94 / 113 | 41 / 67 |
| serious Total, serious adverse events | 0 / 19 | 3 / 18 | 14 / 113 | 5 / 67 |
Outcome results
Primary
Change From Baseline in Total Short Physical Performance Battery (SPPB) Score to Week 25
Change from Baseline in total Short Physical Performance Battery (SPPB) Score to week 25; SPPB is a series of six activities involving three domains of physical function - balance, usual walking speed and rising from a chair , is commonly used globally to assess and quantify (score 0-12) lower extremity function and has been shown to predict future adverse health events. A decline of one or more points in the SPPB total score is predictive of a decrease in lower extremity function and future adverse clinical outcomes in older adults, including falls, hospitalizations, institutionalization, incident disability and death
Time frame: Baseline, week 25
Population: Full Analysis Set (FAS) -comprised all patients to whom study treatment had been assigned. Following the intent to treat principle, patients were analyzed according to treatment assigned at randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BYM338 70 mg | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score to Week 25 | Baseline | 7.1 Score on a scale | Standard Deviation 2.12 |
| BYM338 70 mg | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score to Week 25 | Week 25 | 8.5 Score on a scale | Standard Deviation 2.48 |
| BYM338 210 mg | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score to Week 25 | Week 25 | 8.7 Score on a scale | Standard Deviation 1.64 |
| BYM338 210 mg | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score to Week 25 | Baseline | 7.3 Score on a scale | Standard Deviation 2.11 |
| BYM338 700 mg | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score to Week 25 | Baseline | 7.2 Score on a scale | Standard Deviation 1.63 |
| BYM338 700 mg | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score to Week 25 | Week 25 | 8.7 Score on a scale | Standard Deviation 2.12 |
| Placebo | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score to Week 25 | Baseline | 7.3 Score on a scale | Standard Deviation 1.67 |
| Placebo | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score to Week 25 | Week 25 | 8.4 Score on a scale | Standard Deviation 2.25 |
p-value: 0.27495% CI: [-0.64, 1.21]Mixed Models Analysis
p-value: 0.3295% CI: [-0.83, 1.35]Mixed Models Analysis
p-value: 0.13495% CI: [-0.24, 0.87]Mixed Models Analysis
Secondary
Change From Baseline at Week 25 in the 6 Minute Walk Test (6MWT) Distance
Change from Baseline at Week 25 in the 6 minute walk test (6MWT) distance to measure improvement in physical function
Time frame: Baseline, week 25
Population: Full Analysis Set (FAS) -comprised all patients to whom study treatment had been assigned. Following the intent to treat principle, patients were analyzed according to treatment assigned at randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BYM338 70 mg | Change From Baseline at Week 25 in the 6 Minute Walk Test (6MWT) Distance | Baseline | 293.30 meters | Standard Deviation 91.842 |
| BYM338 70 mg | Change From Baseline at Week 25 in the 6 Minute Walk Test (6MWT) Distance | Week 25 | 304.98 meters | Standard Deviation 102.934 |
| BYM338 210 mg | Change From Baseline at Week 25 in the 6 Minute Walk Test (6MWT) Distance | Week 25 | 340.71 meters | Standard Deviation 72.911 |
| BYM338 210 mg | Change From Baseline at Week 25 in the 6 Minute Walk Test (6MWT) Distance | Baseline | 291.81 meters | Standard Deviation 82.527 |
| BYM338 700 mg | Change From Baseline at Week 25 in the 6 Minute Walk Test (6MWT) Distance | Baseline | 294.30 meters | Standard Deviation 83.602 |
| BYM338 700 mg | Change From Baseline at Week 25 in the 6 Minute Walk Test (6MWT) Distance | Week 25 | 315.32 meters | Standard Deviation 97.02 |
| Placebo | Change From Baseline at Week 25 in the 6 Minute Walk Test (6MWT) Distance | Baseline | 312.43 meters | Standard Deviation 93.924 |
| Placebo | Change From Baseline at Week 25 in the 6 Minute Walk Test (6MWT) Distance | Week 25 | 322.71 meters | Standard Deviation 103.865 |
p-value: 0.57695% CI: [-37.6, 30.95]Mixed Models Analysis
p-value: 0.17895% CI: [-22.2, 61.41]Mixed Models Analysis
p-value: 0.16395% CI: [-10.4, 30.98]Mixed Models Analysis
Secondary
Change From Baseline to Week 25 in Usual Gait Speed (GS) Over 4 Meters
Change from Baseline to Week 25 in usual Gait speed (GS) over 4 meters Gait speed in this study was assessed as part of the SPPB, over a 4 meter distance of a 6 meter course. This test assessed a person's usual walking speed, which was defined as the speed a person normally walks from one place to another without urgency (e.g., walking down a hallway).
Time frame: baseline, week 25
Population: Full Analysis Set (FAS) -comprised all patients to whom study treatment had been assigned. Following the intent to treat principle, patients were analyzed according to treatment assigned at randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BYM338 70 mg | Change From Baseline to Week 25 in Usual Gait Speed (GS) Over 4 Meters | Baseline | 2.37 m/sec | Standard Deviation 0.684 |
| BYM338 70 mg | Change From Baseline to Week 25 in Usual Gait Speed (GS) Over 4 Meters | Week 25 | 3.12 m/sec | Standard Deviation 0.857 |
| BYM338 210 mg | Change From Baseline to Week 25 in Usual Gait Speed (GS) Over 4 Meters | Week 25 | 3.60 m/sec | Standard Deviation 0.699 |
| BYM338 210 mg | Change From Baseline to Week 25 in Usual Gait Speed (GS) Over 4 Meters | Baseline | 2.72 m/sec | Standard Deviation 0.752 |
| BYM338 700 mg | Change From Baseline to Week 25 in Usual Gait Speed (GS) Over 4 Meters | Week 25 | 3.30 m/sec | Standard Deviation 0.902 |
| BYM338 700 mg | Change From Baseline to Week 25 in Usual Gait Speed (GS) Over 4 Meters | Baseline | 2.58 m/sec | Standard Deviation 0.624 |
| Placebo | Change From Baseline to Week 25 in Usual Gait Speed (GS) Over 4 Meters | Week 25 | 3.23 m/sec | Standard Deviation 0.838 |
| Placebo | Change From Baseline to Week 25 in Usual Gait Speed (GS) Over 4 Meters | Baseline | 2.70 m/sec | Standard Deviation 0.493 |
p-value: 0.48895% CI: [-0.1, 0.1]Mixed Models Analysis
p-value: 0.05595% CI: [-0.02, 0.22]Mixed Models Analysis
p-value: 0.16195% CI: [-0.03, 0.09]Mixed Models Analysis
Secondary
Percentage Change From Baseline to Week 25 on Appendicular Skeletal Muscle Index (ASMI) Measured by Dual Energy X-ray Absorptiometry (DXA)
Change from Baseline to Week 25 on appendicular skeletal muscle index (ASMI) measured by Dual Energy X-ray Absorptiometry (DXA) Appendicular skeletal muscle index (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 (m\^2). Therefore, an increase in ASMI indicates an increase in the quantity of an individual's lean mass.
Time frame: baseline, week 25
Population: Full Analysis Set (FAS) -comprised all patients to whom study treatment had been assigned. Following the intent to treat principle, patients were analyzed according to treatment assigned at randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BYM338 70 mg | Percentage Change From Baseline to Week 25 on Appendicular Skeletal Muscle Index (ASMI) Measured by Dual Energy X-ray Absorptiometry (DXA) | Baseline | 5.99 Percent Change | Standard Deviation 0.886 |
| BYM338 70 mg | Percentage Change From Baseline to Week 25 on Appendicular Skeletal Muscle Index (ASMI) Measured by Dual Energy X-ray Absorptiometry (DXA) | Week 25 | 6.04 Percent Change | Standard Deviation 0.947 |
| BYM338 210 mg | Percentage Change From Baseline to Week 25 on Appendicular Skeletal Muscle Index (ASMI) Measured by Dual Energy X-ray Absorptiometry (DXA) | Week 25 | 6.42 Percent Change | Standard Deviation 0.849 |
| BYM338 210 mg | Percentage Change From Baseline to Week 25 on Appendicular Skeletal Muscle Index (ASMI) Measured by Dual Energy X-ray Absorptiometry (DXA) | Baseline | 5.87 Percent Change | Standard Deviation 0.795 |
| BYM338 700 mg | Percentage Change From Baseline to Week 25 on Appendicular Skeletal Muscle Index (ASMI) Measured by Dual Energy X-ray Absorptiometry (DXA) | Baseline | 5.70 Percent Change | Standard Deviation 0.823 |
| BYM338 700 mg | Percentage Change From Baseline to Week 25 on Appendicular Skeletal Muscle Index (ASMI) Measured by Dual Energy X-ray Absorptiometry (DXA) | Week 25 | 6.10 Percent Change | Standard Deviation 0.836 |
| Placebo | Percentage Change From Baseline to Week 25 on Appendicular Skeletal Muscle Index (ASMI) Measured by Dual Energy X-ray Absorptiometry (DXA) | Baseline | 5.55 Percent Change | Standard Deviation 0.753 |
| Placebo | Percentage Change From Baseline to Week 25 on Appendicular Skeletal Muscle Index (ASMI) Measured by Dual Energy X-ray Absorptiometry (DXA) | Week 25 | 5.60 Percent Change | Standard Deviation 0.717 |
p-value: 0.21395% CI: [0.99, 1.03]Mixed Models Analysis
p-value: <0.00195% CI: [1.03, 1.09]Mixed Models Analysis
p-value: <0.00195% CI: [1.05, 1.08]Mixed Models Analysis
Secondary
Percentage Change From Baseline to Week 25 on Total Lean Body Mass Measured by Dual Energy X-ray Absorptiometry (DXA)
Change from Baseline to Week 25 on Total lean body mass and appendicular skeletal muscle index (ASMI) measured by Dual Energy X-ray Absorptiometry (DXA) total lean body mass (LBM) is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(LBM at Visit - LBM at Baseline) / LBM at Baseline\] \* 100.
Time frame: baseline, week 25
Population: Full Analysis Set (FAS) -comprised all patients to whom study treatment had been assigned. Following the intent to treat principle, patients were analyzed according to treatment assigned at randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BYM338 70 mg | Percentage Change From Baseline to Week 25 on Total Lean Body Mass Measured by Dual Energy X-ray Absorptiometry (DXA) | Baseline | 37.44 Percent Change | Standard Deviation 8.507 |
| BYM338 70 mg | Percentage Change From Baseline to Week 25 on Total Lean Body Mass Measured by Dual Energy X-ray Absorptiometry (DXA) | Week 25 | 38.26 Percent Change | Standard Deviation 8.66 |
| BYM338 210 mg | Percentage Change From Baseline to Week 25 on Total Lean Body Mass Measured by Dual Energy X-ray Absorptiometry (DXA) | Week 25 | 39.52 Percent Change | Standard Deviation 8.343 |
| BYM338 210 mg | Percentage Change From Baseline to Week 25 on Total Lean Body Mass Measured by Dual Energy X-ray Absorptiometry (DXA) | Baseline | 35.84 Percent Change | Standard Deviation 7.3 |
| BYM338 700 mg | Percentage Change From Baseline to Week 25 on Total Lean Body Mass Measured by Dual Energy X-ray Absorptiometry (DXA) | Baseline | 35.39 Percent Change | Standard Deviation 8.891 |
| BYM338 700 mg | Percentage Change From Baseline to Week 25 on Total Lean Body Mass Measured by Dual Energy X-ray Absorptiometry (DXA) | Week 25 | 37.86 Percent Change | Standard Deviation 9.064 |
| Placebo | Percentage Change From Baseline to Week 25 on Total Lean Body Mass Measured by Dual Energy X-ray Absorptiometry (DXA) | Baseline | 33.65 Percent Change | Standard Deviation 6.89 |
| Placebo | Percentage Change From Baseline to Week 25 on Total Lean Body Mass Measured by Dual Energy X-ray Absorptiometry (DXA) | Week 25 | 33.95 Percent Change | Standard Deviation 6.921 |
p-value: 0.45895% CI: [0.98, 1.02]Mixed Models Analysis
p-value: <0.00195% CI: [1.03, 1.08]Mixed Models Analysis
p-value: <0.00195% CI: [1.04, 1.07]Mixed Models Analysis