Inclusion Body Myositis
Conditions
Keywords
IBM
Brief summary
Funding Source - FDA Office of Orphan Products Development (OOPD). The purpose of this study is to evaluate the safety and efficacy of the study drug, arimoclomol in IBM patients.
Detailed description
A Phase 2/3, randomized, double-blind, placebo-controlled, international, 20-month intervention study in patients with IBM.
Interventions
DRUGArimoclomol
2 capsules (2 x 124 mg arimoclomol base; equivalent to 2 x 200 mg arimoclomol citrate) taken 3 times daily during breakfast, early afternoon, and at bedtime
OTHERPlacebo
2 matched placebo capsules taken 3 times daily during breakfast, early afternoon, and at bedtime
Sponsors
ZevraDenmark
University of Kansas Medical Center
University College, London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Meet any of the European Neuromuscular Centre Inclusion Body Myositis research diagnostic criteria 2011 categories for IBM. * Demonstrate being able to arise from a chair without support from another person or device. * Able to ambulate at least 20 ft/6 meters with or without assistive device. Once arisen from the chair, participant may use any walking device, i.e. walker/frame, can, crutches, or braces. They cannot be supported by another person and cannot use furniture or wall for support. * Age at onset of weakness \>45 years. * Body weight of \>= 40 kg. * Able to give informed consent.
Exclusion criteria
* History of any of the following excludes subject participation in the study: chronic infection particularly HIV or Hepatitis B or C; cancer other than basal cell cancer less than five years prior; or other chronic serious medical illnesses. * Presence of any of the following on routine blood screening: White blood cells (WBC) \<3000; platelets \< 100,000; hematocrit \<30%; blood urea nitrogen (BUN) \>30 mg/dL; creatinine \>1.5 x upper limit of normal; symptomatic liver disease with serum albumin \<3 g/dL. * History of most recent creatine kinase \>15x the upper limit of normal without any other explanation besides IBM. * History of non-compliance with other therapies. * Use of testosterone except for physiologic replacement doses in case of androgen deficiency. Participants must have documented proof of the androgen deficiency. * Coexistence of other disease that would be likely to affect outcome measures * Drug or alcohol abuse within past three months. * Participation in a recent drug study in the last 30 days prior to the screening visit or use of a biologic agent less than 6 months prior to the screening visit. * Women who are lactating or unwilling to use adequate method of birth control who are not surgically sterile. Adequate birth control includes use of intrauterine device, abstinence, or oral contraceptives or a double barrier method, e.g condom plus diaphragm will be necessary for both male and female participants. * Participants taking \>7.5 mg prednisolone or equivalent or participants on Intravenous Immunoglobulin Therapy (IVIg) or other immunosuppressants within the last 3 months. * Clinically significant renal or hepatic disease, as indicated by clinical laboratory assessment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score | Change from Baseline to Month 20 | Measured by rate of decline in the IBMFRS between experimental and placebo groups. The IBMFRS is a 10-item questionnaire. Scores for each item range from 0 to 4. There is a total maximum score of 40 and minimum score of 0. The higher the score the better functional status of the person. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Manual Muscle Testing (MMT), Total Score | Change from Baseline to Month 12 and Month 20 | The Manual Muscle Testing (MMT) scores the strength of 24 muscles (axial, proximal, and distal muscles, tested bilaterally) on a scale from 0 to 10 points. The total score is calculated as an average across the 24 muscles and ranges from 0 to 10. The total score will increase if a patient is getting stronger and decrease if a patient is getting weaker. |
| Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score | Change from Baseline to Month 12 | Measured by rate of decline in the IBMFRS between experimental and placebo groups. The IBMFRS is a 10-item questionnaire. Scores for each item range from 0 to 4. There is a total maximum score of 40 and minimum score of 0. The higher the score the better functional status of the person. |
| Grip Strength | Change from Baseline to Month 12 and 20 | Unilateral hand grip strength in both hands measured using the Jamar Dynamometer. Results are for the stronger limb, as identified at baseline. |
| 6 Minute Walk Test (6MWT); Distance After 6 Minutes (6MWD) | Change from Baseline to Month 12 and Month 20 | The distance patients could walk in 6 minutes. The distance walked in meters was recorded after 6 minutes. |
| Short Form-36 (SF-36) Physical Component Score | Change from Baseline to Month 12 and Month 20 | Measured using the Short Form health survey with 36 items (SF-36). The questionnaire measures 8 health concepts which yields 2 summary measures: physical and mental health. The physical component score includes 4 scales of physical functioning (10 items), role limitations due to physical health (4 items), bodily pain (2 items), and general health (5 items). To score the SF-36, scales are standardized with a scoring algorithm to obtain a score ranging from 0 to 100, and the summary measure is calculated as the average score. Higher scores indicate better health status. |
| Maximum Voluntary Isometric Contraction (MVICT) of Quadriceps | Change from Baseline to Month 12 and Month 20 | Unilateral strength of the knee extensor muscles on both limbs using the MicroFET hand-held dynamometer. Results are for the stronger limb, as identified at baseline. |
| Health Assessment Questionnaire - Disability Index (HAQ-DI) | Change from Baseline to Month 12 and Month 20 | The disability index of the HAQ measures self-reported functional status (disability) including the patient's use of aids or devices and/or help from other persons. The scale is composed of 20 items in 8 domains (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities). Each domain has at least 2 subcategory items, scored on a scale from 0 to 3, and for each of the 8 domains the domain score was the highest score of the involved subcategory scores. The total score reported is an average over 8 domains and scores from at least 6 domains had to be available for the total score to be calculated. The average total score ranges from 0 to 3, and a higher score corresponds to a worsening in functional status. |
| Modified Timed up and go (mTUG) | Change from Baseline to Month 12 and Month 20 | The patient's combined ability to rise from a chair and walk 3 meters, turn around and walk back to the chair and sit down. The test was performed twice and the fastest time was used. The results were expressed as velocity in meters/second. |
| Short Form-36 (SF-36) Mental Component Score | Change from Baseline to Month 12 and Month 20 | Measured using the Short Form health survey with 36 items (SF-36). The questionnaire measures 8 health concepts which yields 2 summary measures: physical and mental health. The mental component score is composed of energy/fatigue (4 items), social functioning (2 items), role limitations due to emotional problems (3 items), and emotional well-being (5 items). To score the SF-36, scales are standardized with a scoring algorithm to obtain a score ranging from 0 to 100, and the summary measure is calculated as the average score. Higher scores indicate better health status. |
| Patient Global Impression of Severity (PGIS) | Change from Baseline to Month 12 and Month 20 | Patient-reported assessment of the impact of IBM on the ability to complete activities of daily living (e.g. dressing, walking, bathing) at the time of the assessment. The response options for the impact of IBM were none (i.e. no impact), very mild, mild, moderate, severe, and very severe. |
| Patient Global Impression of Change (PGIC) | Change from Baseline to Month 12 and Month 20 | Patient-reported assessment of the change from start of study treatment in the impact of IBM on the ability to complete activities of daily living (e.g. dressing, walking, bathing). The response options for change in impact were very much worse, much worse, a little worse, no change, a little improved, much improved, and very much improved. |
| Clinician Global Impression of Severity (CGIS) | Change from Baseline to Month 12 and Month 20 | Clinician-reported assessment of the severity of the patient's IBM symptoms at the time of the assessment. The response options were none, very mild, mild, moderate, severe, and very severe |
| Clinician Global Impression of Change (CGIC) | Change from Baseline to Month 12 and Month 20 | Clinician-reported assessment of the change from start of study treatment in the patient's IBM symptoms. The response options for change in IBM were very much worse, much worse, a little worse, no change, a little improved, much improved, and very much improved. |
| Falls and Near Falls | Accumulated number from Baseline to Month 20 | Falls and near falls registered by the participants in a diary |
| 2 Minute Walk Test (2MWT) | Change from Baseline to Month 12 and Month 20 | The distance patients could walk in 2 minutes (during the 6 Minute Walk Test) recorded in meters. |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arimoclomol (20 Months) Arimoclomol base 248 mg 3 times daily for 20 months | 73 |
| Placebo (20 Months) Matching placebo 3 times daily for 20 months | 77 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 1 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 3 |
Baseline characteristics
| Characteristic | Total | Arimoclomol (20 Months) | Placebo (20 Months) |
|---|---|---|---|
| Age at diagnosis | 63.4 Years STANDARD_DEVIATION 8.28 | 63.4 Years STANDARD_DEVIATION 8.67 | 63.5 Years STANDARD_DEVIATION 7.94 |
| Age, Continuous | 67.2 Years STANDARD_DEVIATION 8.1 | 67.0 Years STANDARD_DEVIATION 8.18 | 67.4 Years STANDARD_DEVIATION 8.08 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 147 Participants | 72 Participants | 75 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score | 27.41 score on a scale STANDARD_DEVIATION 4.581 | 26.88 score on a scale STANDARD_DEVIATION 4.74 | 27.92 score on a scale STANDARD_DEVIATION 4.394 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 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 | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 143 Participants | 69 Participants | 74 Participants |
| Sex: Female, Male Female | 36 Participants | 20 Participants | 16 Participants |
| Sex: Female, Male Male | 114 Participants | 53 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 73 | 1 / 78 |
| other Total, other adverse events | 72 / 73 | 70 / 78 |
| serious Total, serious adverse events | 11 / 73 | 18 / 78 |
Outcome results
Primary
Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score
Measured by rate of decline in the IBMFRS between experimental and placebo groups. The IBMFRS is a 10-item questionnaire. Scores for each item range from 0 to 4. There is a total maximum score of 40 and minimum score of 0. The higher the score the better functional status of the person.
Time frame: Change from Baseline to Month 20
Population: Intention-to-treat; participants with data at Month 20
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arimoclomol (20 Months) | Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score | -3.26 score on a scale |
| Placebo (20 Months) | Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score | -2.26 score on a scale |
Comparison: The baseline observation was the last observation recorded prior to the first dose of study medication. The change from baseline in IBMFRS total score was analyzed using a Mixed Models for Repeated Measures (MMRM) with treatment interacting with visit and trial site as factors. Baseline IBMFRS total score interacting with visit was further included as covariate. An unstructured covariance matrix was assumed.p-value: 0.114695% CI: [-2.23, 0.24]Mixed Models Analysis
Secondary
2 Minute Walk Test (2MWT)
The distance patients could walk in 2 minutes (during the 6 Minute Walk Test) recorded in meters.
Time frame: Change from Baseline to Month 12 and Month 20
Population: Intention-to-treat; participants with data at Month 12 and Month 20, respectively
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arimoclomol (20 Months) | 2 Minute Walk Test (2MWT) | Change from Baseline to Month 12 | -4.73 meters | Standard Deviation 19.355 |
| Arimoclomol (20 Months) | 2 Minute Walk Test (2MWT) | Change from Baseline to Month 20 | -11.18 meters | Standard Deviation 25.551 |
| Placebo (20 Months) | 2 Minute Walk Test (2MWT) | Change from Baseline to Month 12 | -2.40 meters | Standard Deviation 16.789 |
| Placebo (20 Months) | 2 Minute Walk Test (2MWT) | Change from Baseline to Month 20 | -8.52 meters | Standard Deviation 23.601 |
Secondary
6 Minute Walk Test (6MWT); Distance After 6 Minutes (6MWD)
The distance patients could walk in 6 minutes. The distance walked in meters was recorded after 6 minutes.
Time frame: Change from Baseline to Month 12 and Month 20
Population: Intention-to-treat; participants with data at Month 12 and Month 20, respectively
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arimoclomol (20 Months) | 6 Minute Walk Test (6MWT); Distance After 6 Minutes (6MWD) | Change from Baseline to Month 20 | -37.0 meters | Standard Deviation 80.09 |
| Arimoclomol (20 Months) | 6 Minute Walk Test (6MWT); Distance After 6 Minutes (6MWD) | Change from Baseline to Month 12 | -16.7 meters | Standard Deviation 56.24 |
| Placebo (20 Months) | 6 Minute Walk Test (6MWT); Distance After 6 Minutes (6MWD) | Change from Baseline to Month 20 | -30.9 meters | Standard Deviation 65.68 |
| Placebo (20 Months) | 6 Minute Walk Test (6MWT); Distance After 6 Minutes (6MWD) | Change from Baseline to Month 12 | -10.7 meters | Standard Deviation 43.65 |
Secondary
Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score
Measured by rate of decline in the IBMFRS between experimental and placebo groups. The IBMFRS is a 10-item questionnaire. Scores for each item range from 0 to 4. There is a total maximum score of 40 and minimum score of 0. The higher the score the better functional status of the person.
Time frame: Change from Baseline to Month 12
Population: Intention-to-treat; participants with data at Month 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arimoclomol (20 Months) | Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score | -1.87 score on a scale | Standard Deviation 3.494 |
| Placebo (20 Months) | Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score | -1.03 score on a scale | Standard Deviation 3.127 |
Secondary
Clinician Global Impression of Change (CGIC)
Clinician-reported assessment of the change from start of study treatment in the patient's IBM symptoms. The response options for change in IBM were very much worse, much worse, a little worse, no change, a little improved, much improved, and very much improved.
Time frame: Change from Baseline to Month 12 and Month 20
Population: Intention-to-treat; participants with data at Month 12 and Month 20, respectively
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Arimoclomol (20 Months) | Clinician Global Impression of Change (CGIC) | Month 12 | Very much worse | 0 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Change (CGIC) | Month 12 | Much worse | 1 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Change (CGIC) | Month 12 | A little worse | 2 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Change (CGIC) | Month 12 | No change | 0 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Change (CGIC) | Month 12 | A little improved | 0 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Change (CGIC) | Month 12 | Much improved | 0 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Change (CGIC) | Month 12 | Very much improved | 0 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Change (CGIC) | Month 12 | Missing | 2 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Change (CGIC) | Month 20 | Very much worse | 0 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Change (CGIC) | Month 20 | Much worse | 0 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Change (CGIC) | Month 20 | A little worse | 3 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Change (CGIC) | Month 20 | No change | 2 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Change (CGIC) | Month 20 | A little improved | 0 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Change (CGIC) | Month 20 | Much improved | 0 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Change (CGIC) | Month 20 | Very much improved | 0 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Change (CGIC) | Month 20 | Missing | 0 Participants |
| Placebo (20 Months) | Clinician Global Impression of Change (CGIC) | Month 20 | Missing | 2 Participants |
| Placebo (20 Months) | Clinician Global Impression of Change (CGIC) | Month 12 | Very much worse | 0 Participants |
| Placebo (20 Months) | Clinician Global Impression of Change (CGIC) | Month 20 | Very much worse | 0 Participants |
| Placebo (20 Months) | Clinician Global Impression of Change (CGIC) | Month 12 | Much worse | 0 Participants |
| Placebo (20 Months) | Clinician Global Impression of Change (CGIC) | Month 20 | A little improved | 1 Participants |
| Placebo (20 Months) | Clinician Global Impression of Change (CGIC) | Month 12 | A little worse | 5 Participants |
| Placebo (20 Months) | Clinician Global Impression of Change (CGIC) | Month 20 | Much worse | 1 Participants |
| Placebo (20 Months) | Clinician Global Impression of Change (CGIC) | Month 12 | No change | 0 Participants |
| Placebo (20 Months) | Clinician Global Impression of Change (CGIC) | Month 20 | Very much improved | 0 Participants |
| Placebo (20 Months) | Clinician Global Impression of Change (CGIC) | Month 12 | A little improved | 1 Participants |
| Placebo (20 Months) | Clinician Global Impression of Change (CGIC) | Month 20 | A little worse | 4 Participants |
| Placebo (20 Months) | Clinician Global Impression of Change (CGIC) | Month 12 | Much improved | 0 Participants |
| Placebo (20 Months) | Clinician Global Impression of Change (CGIC) | Month 20 | Much improved | 1 Participants |
| Placebo (20 Months) | Clinician Global Impression of Change (CGIC) | Month 12 | Very much improved | 0 Participants |
| Placebo (20 Months) | Clinician Global Impression of Change (CGIC) | Month 20 | No change | 0 Participants |
| Placebo (20 Months) | Clinician Global Impression of Change (CGIC) | Month 12 | Missing | 3 Participants |
Secondary
Clinician Global Impression of Severity (CGIS)
Clinician-reported assessment of the severity of the patient's IBM symptoms at the time of the assessment. The response options were none, very mild, mild, moderate, severe, and very severe
Time frame: Change from Baseline to Month 12 and Month 20
Population: Intention-to-treat; participants with data at Month 12 and Month 20, respectively
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Arimoclomol (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 12 | None | 0 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 12 | Very mild | 0 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 12 | Mild | 0 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 12 | Moderate | 2 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 12 | Severe | 1 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 12 | Very severe | 0 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 12 | Missing | 2 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 20 | None | 0 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 20 | Very mild | 1 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 20 | Mild | 1 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 20 | Moderate | 2 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 20 | Severe | 1 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 20 | Very severe | 0 Participants |
| Arimoclomol (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 20 | Missing | 0 Participants |
| Placebo (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 20 | Moderate | 2 Participants |
| Placebo (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 12 | None | 0 Participants |
| Placebo (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 20 | None | 0 Participants |
| Placebo (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 12 | Very mild | 0 Participants |
| Placebo (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 20 | Very severe | 0 Participants |
| Placebo (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 12 | Mild | 2 Participants |
| Placebo (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 20 | Very mild | 0 Participants |
| Placebo (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 12 | Moderate | 4 Participants |
| Placebo (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 20 | Severe | 3 Participants |
| Placebo (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 12 | Severe | 0 Participants |
| Placebo (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 20 | Mild | 2 Participants |
| Placebo (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 12 | Very severe | 0 Participants |
| Placebo (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 20 | Missing | 2 Participants |
| Placebo (20 Months) | Clinician Global Impression of Severity (CGIS) | Month 12 | Missing | 3 Participants |
Secondary
Falls and Near Falls
Falls and near falls registered by the participants in a diary
Time frame: Accumulated number from Baseline to Month 20
Population: Intention-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arimoclomol (20 Months) | Falls and Near Falls | Falls/year | 4.8 events (falls or near-falls) per year | Standard Deviation 5.43 |
| Arimoclomol (20 Months) | Falls and Near Falls | Near-falls/year | 9.1 events (falls or near-falls) per year | Standard Deviation 28.52 |
| Placebo (20 Months) | Falls and Near Falls | Falls/year | 5.8 events (falls or near-falls) per year | Standard Deviation 11.71 |
| Placebo (20 Months) | Falls and Near Falls | Near-falls/year | 6.9 events (falls or near-falls) per year | Standard Deviation 17.12 |
Secondary
Grip Strength
Unilateral hand grip strength in both hands measured using the Jamar Dynamometer. Results are for the stronger limb, as identified at baseline.
Time frame: Change from Baseline to Month 12 and 20
Population: Intention-to-treat; participants with data at Month 12 and Month 20, respectively
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arimoclomol (20 Months) | Grip Strength | Change from Baseline to Month 12 | -1.09 kg | Standard Deviation 5.459 |
| Arimoclomol (20 Months) | Grip Strength | Change from Baseline to Month 20 | -3.93 kg | Standard Deviation 9.201 |
| Placebo (20 Months) | Grip Strength | Change from Baseline to Month 12 | -1.84 kg | Standard Deviation 3.259 |
| Placebo (20 Months) | Grip Strength | Change from Baseline to Month 20 | -2.86 kg | Standard Deviation 4.741 |
Secondary
Health Assessment Questionnaire - Disability Index (HAQ-DI)
The disability index of the HAQ measures self-reported functional status (disability) including the patient's use of aids or devices and/or help from other persons. The scale is composed of 20 items in 8 domains (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities). Each domain has at least 2 subcategory items, scored on a scale from 0 to 3, and for each of the 8 domains the domain score was the highest score of the involved subcategory scores. The total score reported is an average over 8 domains and scores from at least 6 domains had to be available for the total score to be calculated. The average total score ranges from 0 to 3, and a higher score corresponds to a worsening in functional status.
Time frame: Change from Baseline to Month 12 and Month 20
Population: Intention-to-treat; participants with data at Month 12 and Month 20, respectively
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arimoclomol (20 Months) | Health Assessment Questionnaire - Disability Index (HAQ-DI) | Change from Baseline to Month 12 | 0.24 score on a scale | Standard Deviation 0.364 |
| Arimoclomol (20 Months) | Health Assessment Questionnaire - Disability Index (HAQ-DI) | Change from Baseline to Month 20 | 0.33 score on a scale | Standard Deviation 0.399 |
| Placebo (20 Months) | Health Assessment Questionnaire - Disability Index (HAQ-DI) | Change from Baseline to Month 12 | 0.24 score on a scale | Standard Deviation 0.375 |
| Placebo (20 Months) | Health Assessment Questionnaire - Disability Index (HAQ-DI) | Change from Baseline to Month 20 | 0.33 score on a scale | Standard Deviation 0.472 |
Secondary
Manual Muscle Testing (MMT), Total Score
The Manual Muscle Testing (MMT) scores the strength of 24 muscles (axial, proximal, and distal muscles, tested bilaterally) on a scale from 0 to 10 points. The total score is calculated as an average across the 24 muscles and ranges from 0 to 10. The total score will increase if a patient is getting stronger and decrease if a patient is getting weaker.
Time frame: Change from Baseline to Month 12 and Month 20
Population: Intention-to-treat; participants with data at Month 12 and Month 20, respectively
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arimoclomol (20 Months) | Manual Muscle Testing (MMT), Total Score | Change from Baseline to Month 12 | -0.49 score on a scale | Standard Deviation 0.878 |
| Arimoclomol (20 Months) | Manual Muscle Testing (MMT), Total Score | Change from Baseline to Month 20 | -0.48 score on a scale | Standard Deviation 0.922 |
| Placebo (20 Months) | Manual Muscle Testing (MMT), Total Score | Change from Baseline to Month 12 | -0.47 score on a scale | Standard Deviation 0.855 |
| Placebo (20 Months) | Manual Muscle Testing (MMT), Total Score | Change from Baseline to Month 20 | -0.53 score on a scale | Standard Deviation 0.764 |
Secondary
Maximum Voluntary Isometric Contraction (MVICT) of Quadriceps
Unilateral strength of the knee extensor muscles on both limbs using the MicroFET hand-held dynamometer. Results are for the stronger limb, as identified at baseline.
Time frame: Change from Baseline to Month 12 and Month 20
Population: Intention-to-treat; participants with data at Month 12 and Month 20, respectively
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arimoclomol (20 Months) | Maximum Voluntary Isometric Contraction (MVICT) of Quadriceps | Change from Baseline to Month 12 | -2.59 kg | Standard Deviation 9.357 |
| Arimoclomol (20 Months) | Maximum Voluntary Isometric Contraction (MVICT) of Quadriceps | Change from Baseline to Month 20 | -6.29 kg | Standard Deviation 12.013 |
| Placebo (20 Months) | Maximum Voluntary Isometric Contraction (MVICT) of Quadriceps | Change from Baseline to Month 12 | -2.49 kg | Standard Deviation 6.067 |
| Placebo (20 Months) | Maximum Voluntary Isometric Contraction (MVICT) of Quadriceps | Change from Baseline to Month 20 | -4.67 kg | Standard Deviation 7.885 |
Secondary
Modified Timed up and go (mTUG)
The patient's combined ability to rise from a chair and walk 3 meters, turn around and walk back to the chair and sit down. The test was performed twice and the fastest time was used. The results were expressed as velocity in meters/second.
Time frame: Change from Baseline to Month 12 and Month 20
Population: Intention-to-treat; participants with data at Month 12 and Month 20, respectively
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arimoclomol (20 Months) | Modified Timed up and go (mTUG) | Change from Baseline to Month 12 | -0.075 meters per second (m/sec) | Standard Deviation 0.3048 |
| Arimoclomol (20 Months) | Modified Timed up and go (mTUG) | Change from Baseline to Month 20 | -0.084 meters per second (m/sec) | Standard Deviation 0.1893 |
| Placebo (20 Months) | Modified Timed up and go (mTUG) | Change from Baseline to Month 12 | -0.058 meters per second (m/sec) | Standard Deviation 0.2281 |
| Placebo (20 Months) | Modified Timed up and go (mTUG) | Change from Baseline to Month 20 | -0.104 meters per second (m/sec) | Standard Deviation 0.1955 |
Secondary
Patient Global Impression of Change (PGIC)
Patient-reported assessment of the change from start of study treatment in the impact of IBM on the ability to complete activities of daily living (e.g. dressing, walking, bathing). The response options for change in impact were very much worse, much worse, a little worse, no change, a little improved, much improved, and very much improved.
Time frame: Change from Baseline to Month 12 and Month 20
Population: Intention-to-treat; participants with data at Month 12 and Month 20, respectively
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Arimoclomol (20 Months) | Patient Global Impression of Change (PGIC) | Month 12 | Very much worse | 1 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Change (PGIC) | Month 12 | Much worse | 10 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Change (PGIC) | Month 12 | A little worse | 27 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Change (PGIC) | Month 12 | No change | 12 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Change (PGIC) | Month 12 | A little improved | 4 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Change (PGIC) | Month 12 | Much improved | 2 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Change (PGIC) | Month 12 | Very much improved | 0 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Change (PGIC) | Month 12 | Missing | 0 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Change (PGIC) | Month 20 | Very much worse | 4 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Change (PGIC) | Month 20 | Much worse | 23 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Change (PGIC) | Month 20 | A little worse | 19 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Change (PGIC) | Month 20 | No change | 5 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Change (PGIC) | Month 20 | A little improved | 3 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Change (PGIC) | Month 20 | Much improved | 2 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Change (PGIC) | Month 20 | Very much improved | 0 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Change (PGIC) | Month 20 | Missing | 0 Participants |
| Placebo (20 Months) | Patient Global Impression of Change (PGIC) | Month 20 | Missing | 0 Participants |
| Placebo (20 Months) | Patient Global Impression of Change (PGIC) | Month 12 | Very much worse | 0 Participants |
| Placebo (20 Months) | Patient Global Impression of Change (PGIC) | Month 20 | Very much worse | 2 Participants |
| Placebo (20 Months) | Patient Global Impression of Change (PGIC) | Month 12 | Much worse | 8 Participants |
| Placebo (20 Months) | Patient Global Impression of Change (PGIC) | Month 20 | A little improved | 2 Participants |
| Placebo (20 Months) | Patient Global Impression of Change (PGIC) | Month 12 | A little worse | 43 Participants |
| Placebo (20 Months) | Patient Global Impression of Change (PGIC) | Month 20 | Much worse | 16 Participants |
| Placebo (20 Months) | Patient Global Impression of Change (PGIC) | Month 12 | No change | 13 Participants |
| Placebo (20 Months) | Patient Global Impression of Change (PGIC) | Month 20 | Very much improved | 0 Participants |
| Placebo (20 Months) | Patient Global Impression of Change (PGIC) | Month 12 | A little improved | 1 Participants |
| Placebo (20 Months) | Patient Global Impression of Change (PGIC) | Month 20 | A little worse | 40 Participants |
| Placebo (20 Months) | Patient Global Impression of Change (PGIC) | Month 12 | Much improved | 0 Participants |
| Placebo (20 Months) | Patient Global Impression of Change (PGIC) | Month 20 | Much improved | 0 Participants |
| Placebo (20 Months) | Patient Global Impression of Change (PGIC) | Month 12 | Very much improved | 0 Participants |
| Placebo (20 Months) | Patient Global Impression of Change (PGIC) | Month 20 | No change | 6 Participants |
| Placebo (20 Months) | Patient Global Impression of Change (PGIC) | Month 12 | Missing | 1 Participants |
Secondary
Patient Global Impression of Severity (PGIS)
Patient-reported assessment of the impact of IBM on the ability to complete activities of daily living (e.g. dressing, walking, bathing) at the time of the assessment. The response options for the impact of IBM were none (i.e. no impact), very mild, mild, moderate, severe, and very severe.
Time frame: Change from Baseline to Month 12 and Month 20
Population: Intention-to-treat; participants with data at Month 12 and Month 20, respectively
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Arimoclomol (20 Months) | Patient Global Impression of Severity (PGIS) | Month 12 | None | 0 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Severity (PGIS) | Month 12 | Very mild | 1 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Severity (PGIS) | Month 12 | Mild | 9 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Severity (PGIS) | Month 12 | Moderate | 31 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Severity (PGIS) | Month 12 | Severe | 14 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Severity (PGIS) | Month 12 | Very severe | 1 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Severity (PGIS) | Month 20 | None | 0 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Severity (PGIS) | Month 20 | Very mild | 2 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Severity (PGIS) | Month 20 | Mild | 8 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Severity (PGIS) | Month 20 | Moderate | 26 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Severity (PGIS) | Month 20 | Severe | 19 Participants |
| Arimoclomol (20 Months) | Patient Global Impression of Severity (PGIS) | Month 20 | Very severe | 1 Participants |
| Placebo (20 Months) | Patient Global Impression of Severity (PGIS) | Month 20 | Severe | 12 Participants |
| Placebo (20 Months) | Patient Global Impression of Severity (PGIS) | Month 12 | None | 1 Participants |
| Placebo (20 Months) | Patient Global Impression of Severity (PGIS) | Month 20 | None | 1 Participants |
| Placebo (20 Months) | Patient Global Impression of Severity (PGIS) | Month 12 | Very mild | 3 Participants |
| Placebo (20 Months) | Patient Global Impression of Severity (PGIS) | Month 20 | Moderate | 43 Participants |
| Placebo (20 Months) | Patient Global Impression of Severity (PGIS) | Month 12 | Mild | 12 Participants |
| Placebo (20 Months) | Patient Global Impression of Severity (PGIS) | Month 20 | Very mild | 2 Participants |
| Placebo (20 Months) | Patient Global Impression of Severity (PGIS) | Month 12 | Moderate | 40 Participants |
| Placebo (20 Months) | Patient Global Impression of Severity (PGIS) | Month 20 | Very severe | 0 Participants |
| Placebo (20 Months) | Patient Global Impression of Severity (PGIS) | Month 12 | Severe | 10 Participants |
| Placebo (20 Months) | Patient Global Impression of Severity (PGIS) | Month 20 | Mild | 8 Participants |
| Placebo (20 Months) | Patient Global Impression of Severity (PGIS) | Month 12 | Very severe | 0 Participants |
Secondary
Short Form-36 (SF-36) Mental Component Score
Measured using the Short Form health survey with 36 items (SF-36). The questionnaire measures 8 health concepts which yields 2 summary measures: physical and mental health. The mental component score is composed of energy/fatigue (4 items), social functioning (2 items), role limitations due to emotional problems (3 items), and emotional well-being (5 items). To score the SF-36, scales are standardized with a scoring algorithm to obtain a score ranging from 0 to 100, and the summary measure is calculated as the average score. Higher scores indicate better health status.
Time frame: Change from Baseline to Month 12 and Month 20
Population: Intention-to-treat; participants with data at Month 12 and Month 20, respectively
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arimoclomol (20 Months) | Short Form-36 (SF-36) Mental Component Score | Change from Baseline to Month 12 | -2.0 score on a scale (mental component) | Standard Deviation 7 |
| Arimoclomol (20 Months) | Short Form-36 (SF-36) Mental Component Score | Change from Baseline to Month 20 | -2.5 score on a scale (mental component) | Standard Deviation 9.19 |
| Placebo (20 Months) | Short Form-36 (SF-36) Mental Component Score | Change from Baseline to Month 12 | -2.1 score on a scale (mental component) | Standard Deviation 7.47 |
| Placebo (20 Months) | Short Form-36 (SF-36) Mental Component Score | Change from Baseline to Month 20 | -1.3 score on a scale (mental component) | Standard Deviation 7.08 |
Secondary
Short Form-36 (SF-36) Physical Component Score
Measured using the Short Form health survey with 36 items (SF-36). The questionnaire measures 8 health concepts which yields 2 summary measures: physical and mental health. The physical component score includes 4 scales of physical functioning (10 items), role limitations due to physical health (4 items), bodily pain (2 items), and general health (5 items). To score the SF-36, scales are standardized with a scoring algorithm to obtain a score ranging from 0 to 100, and the summary measure is calculated as the average score. Higher scores indicate better health status.
Time frame: Change from Baseline to Month 12 and Month 20
Population: Intention-to-treat; participants with data at Month 12 and Month 20, respectively
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arimoclomol (20 Months) | Short Form-36 (SF-36) Physical Component Score | Change from Baseline to Month 12 | -1.3 score on a scale (physical component) | Standard Deviation 5.39 |
| Arimoclomol (20 Months) | Short Form-36 (SF-36) Physical Component Score | Change from Baseline to Month 20 | -1.0 score on a scale (physical component) | Standard Deviation 6.94 |
| Placebo (20 Months) | Short Form-36 (SF-36) Physical Component Score | Change from Baseline to Month 12 | -2.0 score on a scale (physical component) | Standard Deviation 6.21 |
| Placebo (20 Months) | Short Form-36 (SF-36) Physical Component Score | Change from Baseline to Month 20 | -3.4 score on a scale (physical component) | Standard Deviation 6.51 |