Muscle Weakness
Conditions
Brief summary
LY2495655 is an investigational drug being tested for muscle wasting.
Interventions
BIOLOGICALLY2495655
Administered SC
DRUGPlacebo
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
75 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Sustained at least 1 fall within 1 calendar year before study screening. * Requires ≥12 seconds to perform a repeated chair stands test or is unable to complete this test at screening. * Hand grip strength is ≤37 kilograms (kg) for men (81.4 pounds) or ≤21 kg for women (46.2 pounds) at screening. * Can stand up from a chair and walk ≥10 meters without human assistance (gait aids such as cane\[s\], crutches, or walkers are acceptable) at screening. * Able to climb at least 1 step on a staircase without human assistance according to the participant at screening (using handrails is allowed). * Have screening clinical laboratory test results within normal reference range for the population, or have results with acceptable deviations that are judged to be not clinically significant by the investigator.
Exclusion criteria
* Major lower limb pain or neurologic impairment or vestibular vertigo or visual impairment that could severely confound measures of physical performance. * Recent lower limb fracture and/or major lower limb surgery. * Planned major surgical procedure within 6 months following study drug dosing. * Have had a lower extremity amputation of the foot, leg, and/or thigh. * Have a body mass index (BMI) ≥35 kilogram per meter squared (kg/m2). * Severe vitamin D deficiency. * Underlying muscle disease other than age-associated muscle waste or disuse atrophy. * Current use or previous use of any drugs known to influence muscle mass or performance. * Have had a recent neurologic injury (\<6 months before study drug dosing), such as stroke or spinal cord injury. * History of a malignant neoplasm in the 18 months before first study drug dosing. * Have a history or presence of unstable cardiovascular or pulmonary comorbidities. * Have a positive fecal occult blood (FOB) test at screening, or the participant cannot provide a stool sample for FOB testing before first study drug dosing. * Have either severe ongoing liver disease or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2 times upper limit of normal (ULN), alkaline phosphatase (ALP) \>1.5 times ULN, or total bilirubin \>1.5 times ULN at screening. * Have an estimated creatinine clearance \<20 milliliters per minute (mL/minute). * Have a history of severe allergic reaction to a monoclonal antibody. * Are males with a female partner of childbearing potential who do not agree to use contraception during the treatment period of the study and up to 15 weeks after the last dose of investigational product (study drug). * Have known allergies to LY2495655, its constituents, or related compounds. * Have severe active psychiatric disease or cognitive impairment as assessed by the Mini-Mental State Examination (MMSE) score \<22 (for a participant who went to school up to age 15 years or less) or \<24 (for a participant who went to school up to at least age 16), making the participant unlikely to understand the informed consent form or comply with protocol procedures. * Exhibit excessive consumption of alcohol or abuse of drugs. * Have uncontrolled diabetes mellitus. * Have had ocular trauma, ophthalmologic surgery, or eye laser treatment within 6 months before study drug dosing. * Have hyponatremia (serum sodium levels \<135 millimoles/liter (\[mmol/L\]) at screening unless a retest shows normonatremia before study drug dosing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 24 Week Endpoint in Appendicular Lean Body Mass (aLBM) | Baseline to 24 weeks | Change from baseline to 24-week endpoint in aLBM, as measured by dual energy x-ray absorptiometry (DEXA), is presented. Least squares (LS) means were calculated using a mixed model repeated measures (MMRM) with treatment, visit, and treatment-by-visit interaction as fixed effects and baseline aLBM as covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Stair Climbing (StC) Time | Baseline to 24 weeks | Change from baseline to the 24-week endpoint in StC time is presented. StC time was assessed by measuring the fastest time achieved to climb 4 steps on a 4-step staircase (the test was performed 2 times). LS means were calculated using a MMRM with treatment, visit, and treatment-by-visit interaction as fixed effects and baseline StC score as covariate. |
| Change From Baseline in Repeated Chair Stands (RCS) Time | Baseline to 24 weeks | Change from baseline to 24-week endpoint in RCS time is presented. In the RCS test, participants were asked to rise from a chair 5 times as fast as possible with their arms folded on their chest. Performance was measured in seconds, as the time from the initial seated position to the final standing position. LS means were calculated using an MMRM with treatment, visit, and treatment-by-visit interaction as fixed effects and baseline RCS time as covariate. |
| Change From Baseline in Usual Gait Speed (uGS) at 4 Meters | Baseline to 24 weeks | Change from baseline to the 24-week endpoint in uGS is presented. Two attempts to walk a 4-meter distance were made. LS means were calculated using a MMRM with treatment, visit, and treatment-by-visit interaction as fixed effects and baseline uGS as covariate. |
Countries
Argentina, Australia, France, Germany, Sweden, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LY2495655 Participants received a 315-mg dose of LY2495655, administered SC, Q4W for 20 weeks. | 102 |
| Placebo Participants received a LY2495655-matching dose of placebo, administered SC, Q4W for 20 weeks. | 99 |
| Total | 201 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Observation Period | Adverse Event | 1 | 1 |
| Observation Period | Withdrawal by Subject | 0 | 2 |
| Treatment Period 1 | Protocol Violation | 0 | 1 |
| Treatment Period 2 | Adverse Event | 0 | 1 |
| Treatment Period 2 | Protocol Violation | 1 | 0 |
| Treatment Period 2 | Withdrawal by Subject | 1 | 1 |
| Treatment Period 3 | Adverse Event | 0 | 3 |
| Treatment Period 3 | Protocol Violation | 1 | 1 |
| Treatment Period 3 | Sponsor Decision | 1 | 0 |
| Treatment Period 3 | Withdrawal by Subject | 3 | 1 |
| Treatment Period 4 | Adverse Event | 0 | 1 |
| Treatment Period 4 | Death | 1 | 0 |
| Treatment Period 4 | Withdrawal by Subject | 2 | 1 |
| Treatment Period 5 | Adverse Event | 4 | 0 |
| Treatment Period 6 | Adverse Event | 2 | 0 |
| Treatment Period 6 | Lost to Follow-up | 0 | 1 |
| Treatment Period 6 | Sponsor decision | 0 | 1 |
Baseline characteristics
| Characteristic | LY2495655 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 81.84 years STANDARD_DEVIATION 4.73 | 82.57 years STANDARD_DEVIATION 5.2 | 82.20 years STANDARD_DEVIATION 4.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 19 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants | 45 Participants | 93 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 37 Participants | 35 Participants | 72 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 101 Participants | 98 Participants | 199 Participants |
| Region of Enrollment Argentina | 17 Participants | 19 Participants | 36 Participants |
| Region of Enrollment Australia | 19 Participants | 17 Participants | 36 Participants |
| Region of Enrollment France | 13 Participants | 12 Participants | 25 Participants |
| Region of Enrollment Germany | 6 Participants | 7 Participants | 13 Participants |
| Region of Enrollment Sweden | 10 Participants | 8 Participants | 18 Participants |
| Region of Enrollment United States | 37 Participants | 36 Participants | 73 Participants |
| Sex: Female, Male Female | 75 Participants | 65 Participants | 140 Participants |
| Sex: Female, Male Male | 27 Participants | 34 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 90 / 102 | 77 / 99 |
| serious Total, serious adverse events | 27 / 102 | 18 / 99 |
Outcome results
Primary
Change From Baseline to 24 Week Endpoint in Appendicular Lean Body Mass (aLBM)
Change from baseline to 24-week endpoint in aLBM, as measured by dual energy x-ray absorptiometry (DEXA), is presented. Least squares (LS) means were calculated using a mixed model repeated measures (MMRM) with treatment, visit, and treatment-by-visit interaction as fixed effects and baseline aLBM as covariate.
Time frame: Baseline to 24 weeks
Population: All participants who received at least 1 dose of LY2495655 or placebo with evaluable aLBM data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2495655 | Change From Baseline to 24 Week Endpoint in Appendicular Lean Body Mass (aLBM) | 0.303 kilograms (kg) | Standard Error 0.085 |
| Placebo | Change From Baseline to 24 Week Endpoint in Appendicular Lean Body Mass (aLBM) | -0.123 kilograms (kg) | Standard Error 0.083 |
p-value: <0.00195% CI: [0.192, 0.66]Mixed Model Repeated Measures
Secondary
Change From Baseline in Repeated Chair Stands (RCS) Time
Change from baseline to 24-week endpoint in RCS time is presented. In the RCS test, participants were asked to rise from a chair 5 times as fast as possible with their arms folded on their chest. Performance was measured in seconds, as the time from the initial seated position to the final standing position. LS means were calculated using an MMRM with treatment, visit, and treatment-by-visit interaction as fixed effects and baseline RCS time as covariate.
Time frame: Baseline to 24 weeks
Population: All participants who received at least 1 dose of LY2495655 or placebo with evaluable RCS time data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2495655 | Change From Baseline in Repeated Chair Stands (RCS) Time | -1.888 seconds | Standard Error 0.588 |
| Placebo | Change From Baseline in Repeated Chair Stands (RCS) Time | 0.826 seconds | Standard Error 0.551 |
p-value: 0.19190% CI: [-2.4, 0.276]Mixed Model Repeated Measures
Secondary
Change From Baseline in Stair Climbing (StC) Time
Change from baseline to the 24-week endpoint in StC time is presented. StC time was assessed by measuring the fastest time achieved to climb 4 steps on a 4-step staircase (the test was performed 2 times). LS means were calculated using a MMRM with treatment, visit, and treatment-by-visit interaction as fixed effects and baseline StC score as covariate.
Time frame: Baseline to 24 weeks
Population: All participants who received at least 1 dose of LY2495655 or placebo with evaluable StC time data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2495655 | Change From Baseline in Stair Climbing (StC) Time | -0.276 seconds | Standard Error 0.182 |
| Placebo | Change From Baseline in Stair Climbing (StC) Time | 0.184 seconds | Standard Error 0.178 |
p-value: 0.07390% CI: [-0.883, -0.039]Mixed Model Repeated Measures
Secondary
Change From Baseline in Usual Gait Speed (uGS) at 4 Meters
Change from baseline to the 24-week endpoint in uGS is presented. Two attempts to walk a 4-meter distance were made. LS means were calculated using a MMRM with treatment, visit, and treatment-by-visit interaction as fixed effects and baseline uGS as covariate.
Time frame: Baseline to 24 weeks
Population: All participants who received at least 1 dose of LY2495655 or placebo with evaluable uGS data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2495655 | Change From Baseline in Usual Gait Speed (uGS) at 4 Meters | 0.030 meters per second (m/s) | Standard Error 0.017 |
| Placebo | Change From Baseline in Usual Gait Speed (uGS) at 4 Meters | 0.013 meters per second (m/s) | Standard Error 0.017 |
p-value: 0.47890% CI: [-0.023, 0.057]Mixed Model Repeated Measures