Sporadic Inclusion Body Myositis
Conditions
Keywords
sporadic inclusion body myositis,, muscle wasting,, extension study,, BYM338,, bimagrumab,
Brief summary
This extension study will provide data to further evaluate the efficacy, safety, and tolerability of three doses of BYM338 and to assess the long-term effects of BYM338 in patients with sporadic inclusion body myositis. The extension study was planned to consist of a Screening epoch (to assess patient eligibility), followed by a Treatment Period 1 epoch (double-blind and placebo-controlled), and a Treatment Period 2 epoch (open-label). A Post-treatment Follow-up (FUP) epoch was also planned for patients who discontinued prematurely. Patients who complete the core study and qualify for this extension study entered Treatment Period 1 and continued on the study drug to which they were randomized in the core study (either to one of the three bimagrumab doses (1 mg/kg, 3 mg/kg, and 10mg/kg) or placebo) during Treatment Period 1. Thus, Treatment Period 1 was double-blind and placebo-controlled. Participants were to continue in Treatment Period 1 until the dose with the best benefit-risk profile was determined from the core study data and selected (duration of Treatment Period 1 was estimated to be between 6 and 8 months). Once the dose with the best benefit-risk profile was selected, all participants (including those who were receiving placebo) were planned to enter Treatment Period 2 and switch to open-label treatment with bimagrumab at the selected dose. The core study has been completed but since the core study did not meet the primary end point (no bimagrumab dose was identified based on the core study efficacy results) the extension study was terminated as per protocol/sponsor's decision; therefore, no patients had entered Treatment Period 2. Instead, all patients were to return for the End of Treatment Period 1 (EOT1) visit at their next scheduled visit. As per protocol, all patients who discontinued study medication during Treatment Period 1 for any reason, including due to the study having been stopped as per protocol/sponsor's decision, were to have entered and complete the 6-month FUP after their EOT1 visit. Due to the nature of the design of the core and extension studies and termination of study medication in the extension study, the treatment duration for individual patients varied considerably. Consequently, the number of patients contributing data to the efficacy analyses at Week 104 and later timepoints was decreased.
Interventions
DRUGBimagrumab
BYM338, a 150 mg/mL concentrate for solution for i.v. infusion, was provided in colorless glass vials with a rubber stopper and aluminum flip-off caps.
DRUGPlacebo
Matching placebo to BYM338 was provided in colorless glass vials with a rubber stopper and aluminum flip-off caps.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
36 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who completed the core study * Written informed consent must be obtained before any extension study assessment is performed. * Able to communicate well with the investigator. * Willing to participate for the entire duration of the extension study with commitment to follow study requirements and procedures.
Exclusion criteria
* Women who are pregnant * Women of child-bearing potential unless they are using highly effective methods of contraception during dosing and for 6 months after the last BYM338 dose. * Current use of prohibited treatments * History of severe hypersensitivity reaction in the core study * History of adverse event(s) (including those from the core study) prior to the start of study drug in the extension study that, in the judgment of the investigator, taking into account the subject's overall status, prevent the subject from entering the extension study * Clinically significant abnormal liver function tests * Any medical condition or laboratory finding which, in the opinion of the investigator may interfere with participation in the study, might confound the results of the study, or pose an additional safety risk in administering BYM338
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths. | to end of study (up to 14 months, including the 6-month treatment-free follow-up period) | Safety monitoring was conducted throughout the study. AEs starting on or after the day of first administration of extension study drug until last administration of study drug + 56 days are considered. SAEs starting on or after the day of first administration of extension study drug are considered. Deaths which occurred on or after the day of first administration of extension study drug are considered. |
| Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD) | Core study baseline, weeks 52, 78, 104, and >=117 | The 6MWD test measures the distance (in meters) that a participant can walk in a 6 minute time frame. A positive change from baseline indicates improvement. The efficacy analysis and time points were based on windowed visits relative to the first dose of the double-blind treatment in the core study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Estimated Annual Number of Falls Per Participant Within Treatment Group | Core baseline to end of extension double-blind treatment (up to a maximum of 32 months) | Participants documented any fall occurrences in a paper diary during the study. |
| Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score | Core study baseline, week 52, week 78, week 104 and >=week 117 | The SPPB evaluated lower extremities function by testing gait speed, ability to keep standing balance and time to rise from a chair five times. The sub-score for each test ranged from 0 to 4. The summary score, which was a summation of scores from the 3 tests, ranged from 0 to 12. An increase in score indicates improvement in physical performance. A negative change from baseline indicates deterioration. The efficacy analysis and time points were based on windowed visits relative to the first dose of the double-blind treatment in the core study. |
| Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side | Core study baseline, week 52, week 78, week 104 and >=week 117 | Quantitative Muscle Testing (QMT) was used to describe the long-term evolution of quadriceps muscle strength on the right side. The QMT was performed using the same portable fixed dynamometry (PFD) used in the core study. A negative change from baseline indicates deterioration. The efficacy analysis and time points were based on windowed visits relative to the first dose of the double-blind treatment in the core study. |
| Number of Patients With Anti-BYM338 Antibodies | end of double-blind treatment (up to 8 months) | Investigated the development of immunogenicity against BYM338. |
| Change in Muscles of the Thigh | up to 1 year, up to 2 years | Magnetic resonance imaging (MRI) was planned to be used to characterize changes in muscles of the thigh in a subset of patients. |
| Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score | Core study baseline, week 52, week 78, week 104, and >=week 117 | Self-reported physical function was assessed by a newly developed patient reported outcome named sporadic inclusion body myositis (sIBM) functional assessment (sIFA). The sIFA consists of 11 items scored on an 11 point numerical rating scale from 0 (no difficulty) to 10 (unable to do) across 3 domains: upper body functioning, lower body functioning and general functioning. Participants completed the assessment where the recall period was the past week prior to completing the patient reported outcome (PRO). The total score on the sIFA scale ranges from 0 (minimum) to 110 (maximum). Higher values represent a worse outcome. A positive change from baseline indicates deterioration. The efficacy analysis and time points were based on windowed visits relative to the first dose of the double-blind treatment in the core study. |
Countries
Australia, Belgium, Denmark, France, Italy, Japan, Netherlands, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Participants entered extension study treatment period after completing the core study and continued on the study drug to which they were randomized in the core study (one of 3 bimagrumab doses (1mg/kg, 3mg/kg or 10mg/kg) or placebo). Participants discontinued from the treatment period were to enter a 6-month, treatment-free Follow-up Period (FUP).
Pre-assignment details
All participants (N=211) were discontinued from the double-blind treatment period, 178 of whom entered the FUP. Overall 154 participants completed the FUP and 20 discontinued due to subject/guardian decision and 1 for technical reasons. Three discontinued FUP due to death (one each in the 10mg/kg, 3mg/kg, and placebo groups).
Participants by arm
| Arm | Count |
|---|---|
| BYM338/Bimagrumab 10 mg/kg Participants received BYM338 10 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period. | 53 |
| BYM338/Bimagrumab 3 mg/kg Participants received BYM338 3 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.. | 52 |
| BYM338/Bimagrumab 1 mg/kg Participants received BYM338 1 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period. | 51 |
| Placebo Participants received BYM338 1 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period. | 55 |
| Total | 211 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-blind Treatment Epoch | Adverse Event | 1 | 0 | 1 | 0 |
| Double-blind Treatment Epoch | Lack of Efficacy | 0 | 0 | 1 | 0 |
| Double-blind Treatment Epoch | Study Terminated by sponsor | 50 | 51 | 48 | 55 |
| Double-blind Treatment Epoch | Withdrawal by Subject | 2 | 1 | 1 | 0 |
| Post-treatment Follow up Epoch | Death | 1 | 1 | 0 | 1 |
| Post-treatment Follow up Epoch | Technical problems | 0 | 0 | 1 | 0 |
| Post-treatment Follow up Epoch | Withdrawal by Subject | 5 | 4 | 9 | 2 |
Baseline characteristics
| Characteristic | BYM338/Bimagrumab 10 mg/kg | BYM338/Bimagrumab 3 mg/kg | BYM338/Bimagrumab 1 mg/kg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 69.2 Years STANDARD_DEVIATION 8.19 | 67.3 Years STANDARD_DEVIATION 9.04 | 70.0 Years STANDARD_DEVIATION 7.69 | 69.9 Years STANDARD_DEVIATION 7.95 | 69.1 Years STANDARD_DEVIATION 8.24 |
| Sex: Female, Male Female | 18 Participants | 19 Participants | 17 Participants | 19 Participants | 73 Participants |
| Sex: Female, Male Male | 35 Participants | 33 Participants | 34 Participants | 36 Participants | 138 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 53 | 1 / 52 | 1 / 51 | 2 / 55 | 3 / 156 |
| other Total, other adverse events | 40 / 53 | 46 / 52 | 38 / 51 | 43 / 55 | 124 / 156 |
| serious Total, serious adverse events | 12 / 53 | 10 / 52 | 7 / 51 | 8 / 55 | 29 / 156 |
Outcome results
Primary
Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD)
The 6MWD test measures the distance (in meters) that a participant can walk in a 6 minute time frame. A positive change from baseline indicates improvement. The efficacy analysis and time points were based on windowed visits relative to the first dose of the double-blind treatment in the core study.
Time frame: Core study baseline, weeks 52, 78, 104, and >=117
Population: The full analysis set, which consisted of all participants who were assigned to treatment in the core study and who received at least one dose of study drug during the extension, was considered for the analysis. Participants with both core baseline (BL) and post core-BL values for each time point were analyzed for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BYM338/Bimagrumab 10 mg/kg | Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD) | >=Week 117 | -206.65 meters | Standard Deviation 281.923 |
| BYM338/Bimagrumab 10 mg/kg | Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD) | Week 52 (n=53,52,51,54) | 6.88 meters | Standard Deviation 68.948 |
| BYM338/Bimagrumab 10 mg/kg | Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD) | Week 104 | -22.68 meters | Standard Deviation 102.549 |
| BYM338/Bimagrumab 10 mg/kg | Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD) | Week 78 | -5.25 meters | Standard Deviation 122.002 |
| BYM338/Bimagrumab 3 mg/kg | Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD) | Week 78 | -9.73 meters | Standard Deviation 68.302 |
| BYM338/Bimagrumab 3 mg/kg | Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD) | >=Week 117 | -5.0 meters | — |
| BYM338/Bimagrumab 3 mg/kg | Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD) | Week 52 (n=53,52,51,54) | 9.48 meters | Standard Deviation 81.676 |
| BYM338/Bimagrumab 3 mg/kg | Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD) | Week 104 | -50.58 meters | Standard Deviation 118.012 |
| BYM338/Bimagrumab 1 mg/kg | Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD) | Week 52 (n=53,52,51,54) | -14.26 meters | Standard Deviation 81.029 |
| BYM338/Bimagrumab 1 mg/kg | Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD) | >=Week 117 | -53.65 meters | Standard Deviation 114.322 |
| BYM338/Bimagrumab 1 mg/kg | Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD) | Week 104 | -25.08 meters | Standard Deviation 95.737 |
| BYM338/Bimagrumab 1 mg/kg | Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD) | Week 78 | -18.66 meters | Standard Deviation 81.536 |
| Placebo | Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD) | >=Week 117 | 31.60 meters | — |
| Placebo | Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD) | Week 52 (n=53,52,51,54) | -5.98 meters | Standard Deviation 78.817 |
| Placebo | Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD) | Week 78 | -32.78 meters | Standard Deviation 96.494 |
| Placebo | Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD) | Week 104 | -61.30 meters | Standard Deviation 107.399 |
Primary
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths.
Safety monitoring was conducted throughout the study. AEs starting on or after the day of first administration of extension study drug until last administration of study drug + 56 days are considered. SAEs starting on or after the day of first administration of extension study drug are considered. Deaths which occurred on or after the day of first administration of extension study drug are considered.
Time frame: to end of study (up to 14 months, including the 6-month treatment-free follow-up period)
Population: Safety set: The safety set consisted of all participants who received at least one dose of study drug during the extension study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BYM338/Bimagrumab 10 mg/kg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths. | Deaths | 1 Participants |
| BYM338/Bimagrumab 10 mg/kg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths. | Adverse events | 48 Participants |
| BYM338/Bimagrumab 10 mg/kg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths. | Serious adverse events | 12 Participants |
| BYM338/Bimagrumab 3 mg/kg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths. | Deaths | 1 Participants |
| BYM338/Bimagrumab 3 mg/kg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths. | Adverse events | 50 Participants |
| BYM338/Bimagrumab 3 mg/kg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths. | Serious adverse events | 10 Participants |
| BYM338/Bimagrumab 1 mg/kg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths. | Adverse events | 44 Participants |
| BYM338/Bimagrumab 1 mg/kg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths. | Serious adverse events | 7 Participants |
| BYM338/Bimagrumab 1 mg/kg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths. | Deaths | 1 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths. | Adverse events | 49 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths. | Deaths | 2 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths. | Serious adverse events | 8 Participants |
Secondary
Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side
Quantitative Muscle Testing (QMT) was used to describe the long-term evolution of quadriceps muscle strength on the right side. The QMT was performed using the same portable fixed dynamometry (PFD) used in the core study. A negative change from baseline indicates deterioration. The efficacy analysis and time points were based on windowed visits relative to the first dose of the double-blind treatment in the core study.
Time frame: Core study baseline, week 52, week 78, week 104 and >=week 117
Population: The full analysis set, which consisted of all participants who were assigned to treatment in the core study and who received at least one dose of study drug during the extension, was considered for the analysis. Participants with both core baseline (BL) and post core-BL values for each time point were analyzed for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BYM338/Bimagrumab 10 mg/kg | Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side | Week 52 | -6.29 newtons | Standard Deviation 31.121 |
| BYM338/Bimagrumab 10 mg/kg | Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side | Week 104 | -11.92 newtons | Standard Deviation 35.243 |
| BYM338/Bimagrumab 10 mg/kg | Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side | >=Week 117 | 67.64 newtons | — |
| BYM338/Bimagrumab 10 mg/kg | Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side | Week 78 | -9.43 newtons | Standard Deviation 41.285 |
| BYM338/Bimagrumab 3 mg/kg | Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side | >=Week 117 | 33.38 newtons | — |
| BYM338/Bimagrumab 3 mg/kg | Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side | Week 52 | -19.70 newtons | Standard Deviation 77.82 |
| BYM338/Bimagrumab 3 mg/kg | Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side | Week 78 | -23.76 newtons | Standard Deviation 73.729 |
| BYM338/Bimagrumab 3 mg/kg | Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side | Week 104 | -16.99 newtons | Standard Deviation 34.379 |
| BYM338/Bimagrumab 1 mg/kg | Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side | >=Week 117 | -19.36 newtons | Standard Deviation 18.475 |
| BYM338/Bimagrumab 1 mg/kg | Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side | Week 104 | -18.63 newtons | Standard Deviation 37.968 |
| BYM338/Bimagrumab 1 mg/kg | Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side | Week 52 | -5.62 newtons | Standard Deviation 32.245 |
| BYM338/Bimagrumab 1 mg/kg | Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side | Week 78 | -17.04 newtons | Standard Deviation 25.696 |
| Placebo | Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side | Week 52 | -14.22 newtons | Standard Deviation 27.577 |
| Placebo | Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side | Week 78 | -21.02 newtons | Standard Deviation 31.391 |
| Placebo | Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side | Week 104 | -21.91 newtons | Standard Deviation 39.985 |
| Placebo | Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side | >=Week 117 | -18.24 newtons | — |
Secondary
Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score
The SPPB evaluated lower extremities function by testing gait speed, ability to keep standing balance and time to rise from a chair five times. The sub-score for each test ranged from 0 to 4. The summary score, which was a summation of scores from the 3 tests, ranged from 0 to 12. An increase in score indicates improvement in physical performance. A negative change from baseline indicates deterioration. The efficacy analysis and time points were based on windowed visits relative to the first dose of the double-blind treatment in the core study.
Time frame: Core study baseline, week 52, week 78, week 104 and >=week 117
Population: The full analysis set, which consisted of all participants who were assigned to treatment in the core study and who received at least one dose of study drug during the extension, was considered for the analysis. Participants with both core baseline (BL) and post core-BL values for each time point were analyzed for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BYM338/Bimagrumab 10 mg/kg | Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score | Week 104 | -1.4 score on a scale | Standard Deviation 3.29 |
| BYM338/Bimagrumab 10 mg/kg | Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score | >=Week 117 | -3.0 score on a scale | Standard Deviation 4.24 |
| BYM338/Bimagrumab 10 mg/kg | Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score | Week 52 | 0.3 score on a scale | Standard Deviation 1.73 |
| BYM338/Bimagrumab 10 mg/kg | Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score | Week 78 | -0.5 score on a scale | Standard Deviation 2.58 |
| BYM338/Bimagrumab 3 mg/kg | Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score | >=Week 117 | 0.0 score on a scale | — |
| BYM338/Bimagrumab 3 mg/kg | Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score | Week 52 | 0.2 score on a scale | Standard Deviation 1.61 |
| BYM338/Bimagrumab 3 mg/kg | Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score | Week 78 | -0.1 score on a scale | Standard Deviation 1.54 |
| BYM338/Bimagrumab 3 mg/kg | Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score | Week 104 | -0.9 score on a scale | Standard Deviation 2.77 |
| BYM338/Bimagrumab 1 mg/kg | Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score | Week 52 | -0.4 score on a scale | Standard Deviation 1.74 |
| BYM338/Bimagrumab 1 mg/kg | Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score | >=Week 117 | 0.3 score on a scale | Standard Deviation 2.06 |
| BYM338/Bimagrumab 1 mg/kg | Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score | Week 78 | -0.4 score on a scale | Standard Deviation 1.69 |
| BYM338/Bimagrumab 1 mg/kg | Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score | Week 104 | -1.1 score on a scale | Standard Deviation 2.56 |
| Placebo | Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score | Week 78 | -0.9 score on a scale | Standard Deviation 1.92 |
| Placebo | Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score | >=Week 117 | 0.0 score on a scale | — |
| Placebo | Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score | Week 104 | -1.3 score on a scale | Standard Deviation 2.35 |
| Placebo | Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score | Week 52 | -0.3 score on a scale | Standard Deviation 1.31 |
Secondary
Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score
Self-reported physical function was assessed by a newly developed patient reported outcome named sporadic inclusion body myositis (sIBM) functional assessment (sIFA). The sIFA consists of 11 items scored on an 11 point numerical rating scale from 0 (no difficulty) to 10 (unable to do) across 3 domains: upper body functioning, lower body functioning and general functioning. Participants completed the assessment where the recall period was the past week prior to completing the patient reported outcome (PRO). The total score on the sIFA scale ranges from 0 (minimum) to 110 (maximum). Higher values represent a worse outcome. A positive change from baseline indicates deterioration. The efficacy analysis and time points were based on windowed visits relative to the first dose of the double-blind treatment in the core study.
Time frame: Core study baseline, week 52, week 78, week 104, and >=week 117
Population: The full analysis set, which consisted of all participants who were assigned to treatment in the core study and who received at least one dose of study drug during the extension, was considered for the analysis. Participants with both core baseline (BL) and post core-BL values for each time point were analyzed for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BYM338/Bimagrumab 10 mg/kg | Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score | Week 78 | -0.27 score on a scale | Standard Deviation 13.745 |
| BYM338/Bimagrumab 10 mg/kg | Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score | >=Week 117 | -16.37 score on a scale | Standard Deviation 21.857 |
| BYM338/Bimagrumab 10 mg/kg | Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score | Week 52 | -1.34 score on a scale | Standard Deviation 15.249 |
| BYM338/Bimagrumab 10 mg/kg | Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score | Week 104 | 3.54 score on a scale | Standard Deviation 14.998 |
| BYM338/Bimagrumab 3 mg/kg | Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score | Week 78 | 5.33 score on a scale | Standard Deviation 13.099 |
| BYM338/Bimagrumab 3 mg/kg | Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score | Week 52 | 1.80 score on a scale | Standard Deviation 11.91 |
| BYM338/Bimagrumab 3 mg/kg | Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score | Week 104 | 8.04 score on a scale | Standard Deviation 16.861 |
| BYM338/Bimagrumab 3 mg/kg | Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score | >=Week 117 | 10.91 score on a scale | — |
| BYM338/Bimagrumab 1 mg/kg | Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score | Week 104 | 5.97 score on a scale | Standard Deviation 12.849 |
| BYM338/Bimagrumab 1 mg/kg | Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score | Week 78 | 6.52 score on a scale | Standard Deviation 12.918 |
| BYM338/Bimagrumab 1 mg/kg | Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score | Week 52 | 3.17 score on a scale | Standard Deviation 11.38 |
| BYM338/Bimagrumab 1 mg/kg | Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score | >=Week 117 | 1.37 score on a scale | Standard Deviation 17.655 |
| Placebo | Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score | Week 104 | 7.39 score on a scale | Standard Deviation 15.58 |
| Placebo | Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score | >=Week 117 | 6.36 score on a scale | — |
| Placebo | Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score | Week 78 | 7.41 score on a scale | Standard Deviation 14.41 |
| Placebo | Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score | Week 52 | 5.16 score on a scale | Standard Deviation 13.889 |
Secondary
Change in Muscles of the Thigh
Magnetic resonance imaging (MRI) was planned to be used to characterize changes in muscles of the thigh in a subset of patients.
Time frame: up to 1 year, up to 2 years
Population: No participants were analyzed. The optional MRI assessment was not initiated as the study was stopped.
Secondary
Estimated Annual Number of Falls Per Participant Within Treatment Group
Participants documented any fall occurrences in a paper diary during the study.
Time frame: Core baseline to end of extension double-blind treatment (up to a maximum of 32 months)
Population: Safety set: The safety set consisted of all participants who were assigned to treatment in the core study and who received at least one dose of study drug during the extension.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BYM338/Bimagrumab 10 mg/kg | Estimated Annual Number of Falls Per Participant Within Treatment Group | 4.164 Annual number of falls per participant |
| BYM338/Bimagrumab 3 mg/kg | Estimated Annual Number of Falls Per Participant Within Treatment Group | 3.879 Annual number of falls per participant |
| BYM338/Bimagrumab 1 mg/kg | Estimated Annual Number of Falls Per Participant Within Treatment Group | 3.480 Annual number of falls per participant |
| Placebo | Estimated Annual Number of Falls Per Participant Within Treatment Group | 3.835 Annual number of falls per participant |
Secondary
Number of Patients With Anti-BYM338 Antibodies
Investigated the development of immunogenicity against BYM338.
Time frame: end of double-blind treatment (up to 8 months)
Population: Safety set: The safety set consisted of all participants who were assigned to treatment in the core study and who received at least one dose of study drug during the extension. Only those participants who provided a sample were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BYM338/Bimagrumab 10 mg/kg | Number of Patients With Anti-BYM338 Antibodies | 0 Participants |
| BYM338/Bimagrumab 3 mg/kg | Number of Patients With Anti-BYM338 Antibodies | 1 Participants |
| BYM338/Bimagrumab 1 mg/kg | Number of Patients With Anti-BYM338 Antibodies | 0 Participants |
| Placebo | Number of Patients With Anti-BYM338 Antibodies | 2 Participants |