Sporadic Inclusion Body Myositis
Conditions
Keywords
sporadic inclusion body myositis,, myositis,, muscle wasting,, controlled clinical trial,, randomized,, body mass,, muscle function,, strength,, performance,, physical function
Brief summary
This study evaluated the efficacy, safety and tolerability of multiple doses of bimagrumab/BYM338 vs placebo, when administered intravenously (i.v.), on physical function, muscle strength, and mobility in patients with sporadic inclusion body myositis (sIBM).
Interventions
DRUGBYM338/bimagrumab
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
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
36 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosed with sporadic inclusion body myositis; * Must be able to walk (assistive aids allowed, including intermittent use of wheelchair); Key
Exclusion criteria
* Must not have other conditions that significantly limit ability to move around; * Must not be using corticosteroids. Must not have used systemic corticosteroid (at daily dose \>=10mg prednisone) for the past 3 months; * Must meet cardiovascular requirements; * Must not be pregnant or nursing; * Must not have a chronic active infection (e.g., HIV, hepatitis B or C, tuberculosis, etc.);
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 6 Minute Walking Distance (6MWD) Test at Week 52 | Baseline, Week 52 | The 6MWD test measured the distance (in meters) that a participant walked in a 6 minute timeframe. A positive change from baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Estimated Within Treatment Group Lean Body Mass (LBM) Ratio at Week 52 | Baseline, Week 52 | LBM was measured via dual energy x-ray absorptiometry (DXA) and calculated as (LBM at Week 52/LBM at baseline)\*100 . A positive change from baseline indicates improvement. |
| Change From Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side at Week 52 | Baseline, Week 52 | Quadriceps muscle strength was measured by portable fixed dynamometry (PFD) on the right side. A negative change from baseline indicates deterioration. |
| Change From Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score at Week 52 | Baseline, Week 52 | 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. |
| Estimated Annual Number of Falls Per Patient Within Treatment Group | Week 52 | Participants documented any fall occurrences in a paper diary during the study. |
| Change From Baseline in Short Physical Performance Battery (SPPB) Score at Week 52 | Baseline, Week 52 | 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. |
Countries
Australia, Belgium, Denmark, France, Italy, Japan, Netherlands, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Participants were randomized into one of the four treatment arms in a 1:1:1:1 ratio.
Pre-assignment details
The study included 4 epochs: screening (up to 28 days pre-treatment), treatment (from day 1 up to 52 weeks), treatment maintenance (from week 52 up to 104 weeks) and follow-up (28 days after last dose administration).
Participants by arm
| Arm | Count |
|---|---|
| BYM338/Bimagrumab 10 mg/kg Participants received study medication with BYM338 at 10 mg/kg from Day 1 to Week 52 and up to Week 104, administered by intravenous (i.v.) infusion every 4 weeks. | 63 |
| BYM338/Bimagrumab 3 mg/kg Participants received study medication with BYM338 at 3 mg/kg from Day 1 to Week 52 and up to Week 104, administered by i.v. infusion every 4 weeks. | 63 |
| BYM338/Bimagrumab 1 mg/kg Participants received study medication with BYM338 at 1 mg/kg from Day 1 to Week 52 and up to Week 104, administered by i.v. infusion every 4 weeks. | 63 |
| Placebo Participants received matching placebo to BYM338 from Day 1 to Week 52 and up to Week 104, administered by i.v. infusion every 4 weeks. | 62 |
| Total | 251 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Follow-up | Adverse Event | 1 | 4 | 0 | 1 |
| Follow-up | Non-compliance with study treatment | 0 | 0 | 0 | 1 |
| Follow-up | Physician Decision | 0 | 0 | 1 | 0 |
| Follow-up | Withdrawal by Subject | 0 | 2 | 0 | 2 |
| Maintenance Treatment Epoch | Adverse Event | 0 | 0 | 1 | 0 |
| Maintenance Treatment Epoch | Withdrawal by Subject | 0 | 1 | 1 | 2 |
| Treatment Epoch | Adverse Event | 3 | 5 | 3 | 1 |
| Treatment Epoch | Death | 1 | 0 | 0 | 0 |
| Treatment Epoch | Non-compliance with study treatment | 0 | 0 | 0 | 1 |
| Treatment Epoch | Physician Decision | 1 | 0 | 0 | 0 |
| Treatment Epoch | Protocol deviation | 0 | 0 | 1 | 1 |
| Treatment Epoch | Withdrawal by Subject | 4 | 3 | 3 | 2 |
Baseline characteristics
| Characteristic | BYM338/Bimagrumab 10 mg/kg | BYM338/Bimagrumab 3 mg/kg | BYM338/Bimagrumab 1 mg/kg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 68.0 Years STANDARD_DEVIATION 7.93 | 66.5 Years STANDARD_DEVIATION 8.72 | 69.4 Years STANDARD_DEVIATION 7.91 | 68.4 Years STANDARD_DEVIATION 8.12 | 68.1 Years STANDARD_DEVIATION 8.2 |
| Sex: Female, Male Female | 22 Participants | 21 Participants | 23 Participants | 23 Participants | 89 Participants |
| Sex: Female, Male Male | 41 Participants | 42 Participants | 40 Participants | 39 Participants | 162 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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 63 / 63 | 63 / 63 | 63 / 63 | 61 / 62 |
| serious Total, serious adverse events | 21 / 63 | 11 / 63 | 18 / 63 | 20 / 62 |
Outcome results
Primary
Change From Baseline in 6 Minute Walking Distance (6MWD) Test at Week 52
The 6MWD test measured the distance (in meters) that a participant walked in a 6 minute timeframe. A positive change from baseline indicates improvement.
Time frame: Baseline, Week 52
Population: The Full Analysis Set (FAS), which included all randomized participants who had received at least one dose of study drug and had at least one post-baseline efficacy assessment, was considered for the analysis. Only those participants from the FAS who had both baseline and week 52 6MWD measurements were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BYM338/Bimagrumab 10 mg/kg | Change From Baseline in 6 Minute Walking Distance (6MWD) Test at Week 52 | 8.63 meters | Standard Error 10.934 |
| BYM338/Bimagrumab 3 mg/kg | Change From Baseline in 6 Minute Walking Distance (6MWD) Test at Week 52 | 9.63 meters | Standard Error 10.77 |
| BYM338/Bimagrumab 1 mg/kg | Change From Baseline in 6 Minute Walking Distance (6MWD) Test at Week 52 | -10.27 meters | Standard Error 10.718 |
| Placebo | Change From Baseline in 6 Minute Walking Distance (6MWD) Test at Week 52 | -8.96 meters | Standard Error 10.765 |
p-value: 0.22199% CI: [-19.63, 54.8]mixed model repeated measures
p-value: 0.190999% CI: [-18.21, 55.4]mixed model repeated measure
p-value: 0.926399% CI: [-37.97, 35.36]mixed models repeated measures
Secondary
Change From Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side at Week 52
Quadriceps muscle strength was measured by portable fixed dynamometry (PFD) on the right side. A negative change from baseline indicates deterioration.
Time frame: Baseline, Week 52
Population: The Full Analysis Set (FAS), which included all randomized participants who had received at least one dose of study drug and had at least one post-baseline efficacy assessment, was considered for the analysis. Only those participants from the FAS who had both baseline and week 52 QMT measurements were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BYM338/Bimagrumab 10 mg/kg | Change From Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side at Week 52 | -12.44 newtons | Standard Error 6.021 |
| BYM338/Bimagrumab 3 mg/kg | Change From Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side at Week 52 | -20.36 newtons | Standard Error 5.843 |
| BYM338/Bimagrumab 1 mg/kg | Change From Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side at Week 52 | -14.89 newtons | Standard Error 5.828 |
| Placebo | Change From Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side at Week 52 | -16.48 newtons | Standard Error 5.83 |
Secondary
Change From Baseline in Short Physical Performance Battery (SPPB) Score at Week 52
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.
Time frame: Baseline, Week 52
Population: The Full Analysis Set (FAS), which included all randomized participants who had received at least one dose of study drug and had at least one post-baseline efficacy assessment, was analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BYM338/Bimagrumab 10 mg/kg | Change From Baseline in Short Physical Performance Battery (SPPB) Score at Week 52 | 0.0 score on a scale | Standard Error 0.24 |
| BYM338/Bimagrumab 3 mg/kg | Change From Baseline in Short Physical Performance Battery (SPPB) Score at Week 52 | 0.0 score on a scale | Standard Error 0.23 |
| BYM338/Bimagrumab 1 mg/kg | Change From Baseline in Short Physical Performance Battery (SPPB) Score at Week 52 | -0.5 score on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline in Short Physical Performance Battery (SPPB) Score at Week 52 | -0.5 score on a scale | Standard Error 0.23 |
Secondary
Change From Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score at Week 52
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.
Time frame: Baseline, Week 52
Population: The Full Analysis Set (FAS), which included all randomized participants who had received at least one dose of study drug and had at least one post-baseline efficacy assessment, was considered for the analysis. Only those participants from the FAS who had both baseline and week 52 sIFA measurements were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BYM338/Bimagrumab 10 mg/kg | Change From Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score at Week 52 | 1.74 score on a scale | Standard Error 1.915 |
| BYM338/Bimagrumab 3 mg/kg | Change From Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score at Week 52 | 3.56 score on a scale | Standard Error 1.876 |
| BYM338/Bimagrumab 1 mg/kg | Change From Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score at Week 52 | 6.12 score on a scale | Standard Error 1.899 |
| Placebo | Change From Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score at Week 52 | 6.85 score on a scale | Standard Error 1.895 |
Secondary
Estimated Annual Number of Falls Per Patient Within Treatment Group
Participants documented any fall occurrences in a paper diary during the study.
Time frame: Week 52
Population: The Full Analysis Set (FAS), which included all randomized participants who had received at least one dose of study drug and had at least one post-baseline efficacy assessment, was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BYM338/Bimagrumab 10 mg/kg | Estimated Annual Number of Falls Per Patient Within Treatment Group | 4.33 Annual number of falls per participant |
| BYM338/Bimagrumab 3 mg/kg | Estimated Annual Number of Falls Per Patient Within Treatment Group | 4.02 Annual number of falls per participant |
| BYM338/Bimagrumab 1 mg/kg | Estimated Annual Number of Falls Per Patient Within Treatment Group | 4.70 Annual number of falls per participant |
| Placebo | Estimated Annual Number of Falls Per Patient Within Treatment Group | 5.13 Annual number of falls per participant |
Secondary
Estimated Within Treatment Group Lean Body Mass (LBM) Ratio at Week 52
LBM was measured via dual energy x-ray absorptiometry (DXA) and calculated as (LBM at Week 52/LBM at baseline)\*100 . A positive change from baseline indicates improvement.
Time frame: Baseline, Week 52
Population: The Full Analysis Set (FAS), which included all randomized participants who had received at least one dose of study drug and had at least one post-baseline efficacy assessment, was considered for the analysis. Only those participants from the FAS who had both baseline and week 52 LBM measurements were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BYM338/Bimagrumab 10 mg/kg | Estimated Within Treatment Group Lean Body Mass (LBM) Ratio at Week 52 | 102.8 Percentage |
| BYM338/Bimagrumab 3 mg/kg | Estimated Within Treatment Group Lean Body Mass (LBM) Ratio at Week 52 | 100.4 Percentage |
| BYM338/Bimagrumab 1 mg/kg | Estimated Within Treatment Group Lean Body Mass (LBM) Ratio at Week 52 | 98.3 Percentage |
| Placebo | Estimated Within Treatment Group Lean Body Mass (LBM) Ratio at Week 52 | 97.2 Percentage |