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This study assessed the efficacy, safety and tolerability of BAF312 administered orally in patients with clinically active polymyositis and also in patients with polymyositis who had shown inadequate response to corticosteroids and or DMARDs (disease modifying antirheumatic drugs).
This study was stopped prematurely due to overall slow recruitment and no evidence for efficacy in a parallel study in dermatomyositis with an assumed similar pathophysiology. With very small sample sizes per group the overall results for this study including primary and all other efficacy and PD data are inconclusive
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | 5 placebo tablets daily during non-titration phase |
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| BAF312 2mg | Experimental | 1 tablet of BAF312 2 mg + 4 tablets of Placebo daily during non-titration phase |
|
| BAF312 10 mg | Experimental | 5 tablets of BAF312 2 mg daily during non-titration phase |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Matching placebo tablet for oral administration |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline at Week 12 for BAF312 2 mg, 10 mg or Placebo (Once Daily) for Combined Efficacy Endpoint: Manual Muscle Testing in 24 Muscles (MMT24) | Manual Muscle Testing Scoring Sheet: Neck flexors, neck extensors and other designated muscles bilaterally (Biceps brachii, Deltoid middle, Quadriceps, Gluteus maximus, Gluteus medius, Trapezius, Iliopsoas, Hamstrings, Wrist extensors, Wrist Flexors, Ankle plantar flexors and Ankle dorsiflexors) were tested on a 0-10 scale by the Investigator. Posterior credibility interval from Bayesian analysis displayed as confidence interval. The scores range was 0 to 260. Higher scores indicate better outcome. | Baseline, at 12 weeks |
| Percent Change From Baseline at Week 12 for BAF312 2 mg, 10 mg or Placebo (Once Daily) Serum Creatine Kinase (CK) Levels | Serum creatine kinase (CK) were analyzed as part of the blood chemistry panel. Posterior credibility interval from Bayesian analysis displayed as confidence interval. The variable CK was log-transformed for statistical analysis and after estimation was converted to percent change from baseline divided by the mean baseline | Baseline, at 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Six-minute Walking Distance (6MWD) at Week 12 | This test assessed the distance a patient could walk in 6 minutes (Rutkove et al 2002). If the patient was not able to walk for 6 minutes then a 2 minute walking test was conducted | Baseline, 12 weeks |
| Six-minute Walking Distance (6MWD) at Week 24 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Phoenix | Arizona | 85013 | United States | ||
| Novartis Investigative Site |
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| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on novartisclinicaltrials.com | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | BAF312 2mg/BAF312 2mg | Patients in Period 1 continue on same 2 mg dose of BAF312 in Period 2 |
| FG001 | BAF312 10 mg/BAF312 10 mg | Patients in Period 1 continue on same 10 mg dose of BAF312 in Period 2 |
| FG002 | Placebo/BAF312 2 mg | Patients on placebo in Period 1 switch to active 2 mg BAF312 in Period 2 |
| FG003 | Placebo/BAF312 10 mg | Patients on placebo in Period 1 switch to active 10 mg BAF312 in Period 2 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 - Randomized |
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| ||||||||||||||||||
| Extension - All Active |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | BAF312 2mg/BAF312 2mg | Patients in Period 1 continue on same 2 mg dose of BAF312 in Period 2 |
| BG001 | BAF312 10 mg/BAF312 10 mg | Patients in Period 1 continue on same 10 mg dose of BAF312 in Period 2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline at Week 12 for BAF312 2 mg, 10 mg or Placebo (Once Daily) for Combined Efficacy Endpoint: Manual Muscle Testing in 24 Muscles (MMT24) | Manual Muscle Testing Scoring Sheet: Neck flexors, neck extensors and other designated muscles bilaterally (Biceps brachii, Deltoid middle, Quadriceps, Gluteus maximus, Gluteus medius, Trapezius, Iliopsoas, Hamstrings, Wrist extensors, Wrist Flexors, Ankle plantar flexors and Ankle dorsiflexors) were tested on a 0-10 scale by the Investigator. Posterior credibility interval from Bayesian analysis displayed as confidence interval. The scores range was 0 to 260. Higher scores indicate better outcome. | Pharmacodynamic (PD) included patients with PD data and no major protocol deviations | Posted | Mean | 90% Confidence Interval | scores on a scale | Baseline, at 12 weeks |
|
Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Period 1 BAF312 2mg | Period 1 BAF312 2mg |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Haemolytic anaemia | Blood and lymphatic system disorders | MedDRA (19.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | Novartis.email@novartis.com |
| ID | Term |
|---|---|
| D017285 | Polymyositis |
| D009220 | Myositis |
| D018979 | Myositis, Inclusion Body |
| ID | Term |
|---|---|
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C578989 | siponimod |
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| BAF312 |
| Drug |
BAF312 in 4 dosage strengths in tablet form: 0.25 mg, 0.5 mg, 1 mg, 2 mg for oral administration |
|
This test assessed the distance a patient could walk in 6 minutes (Rutkove et al 2002). If the patient was not able to walk for 6 minutes then a 2 minute walking test was conducted |
| Baseline, 24 weeks |
| BAF312 Trough Plasma Concentrations (PK Set) | All blood samples were taken by either direct venipuncture or an indwelling cannula inserted in a forearm vein. For each sample, approximately 2 mL of blood was drawn. BAF312 was determined in ethylenediaminetetraacetic acid (EDTA) plasma using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical method for the quantification. The anticipated lower limit of quantification (LLOQ) was 0.02 ng/mL using 0.1 mL of plasma | -7 Baseline, day 28, 56, 84 |
| Torono |
| Ontario |
| M5G 2C4 |
| Canada |
| Novartis Investigative Site | Prague | 128 50 | Czechia |
| Novartis Investigative Site | Budapest | 1083 | Hungary |
| Novartis Investigative Site | Debrecen | 4032 | Hungary |
| Novartis Investigative Site | Bydgoszcz | 85-168 | Poland |
| Novartis Investigative Site | Taichung | 40447 | Taiwan |
| Novartis Investigative Site | Taichung | 40705 | Taiwan |
| COMPLETED |
|
| NOT COMPLETED |
|
| BG002 | Placebo/BAF312 2 mg | Patients on placebo in Period 1 switch to active 2 mg BAF312 in Period 2 |
| BG003 | Placebo/BAF312 10 mg | Patients on placebo in Period 1 switch to active 10 mg BAF312 in Period 2 |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Disease duration | Mean | Standard Deviation | years |
|
| Baseline MMT24 Score | Manual muscle testing in 24 muscle groups (MMT24). The scores range was 0 to 260. Higher scores indicate better outcome. | Mean | Standard Deviation | scores on a scale |
|
| Taking DMARD at baseline | Taking a disease-modifying antirheumatic drugs | Number | participants |
|
| OG001 | BAF312 10 mg | 5 tablets of BAF312 2 mg daily during Period 1 |
| OG002 | Placebo | matching placebo |
|
|
|
| Primary | Percent Change From Baseline at Week 12 for BAF312 2 mg, 10 mg or Placebo (Once Daily) Serum Creatine Kinase (CK) Levels | Serum creatine kinase (CK) were analyzed as part of the blood chemistry panel. Posterior credibility interval from Bayesian analysis displayed as confidence interval. The variable CK was log-transformed for statistical analysis and after estimation was converted to percent change from baseline divided by the mean baseline | Pharmacodynamic (PD) included patients with PD data and no major protocol deviations | Posted | Mean | 90% Confidence Interval | U/L | Baseline, at 12 weeks |
|
|
|
| Secondary | Six-minute Walking Distance (6MWD) at Week 12 | This test assessed the distance a patient could walk in 6 minutes (Rutkove et al 2002). If the patient was not able to walk for 6 minutes then a 2 minute walking test was conducted | Pharmacodynamic (PD) included patients with PD data and no major protocol deviations | Posted | Mean | Standard Deviation | meters | Baseline, 12 weeks |
|
|
|
| Secondary | Six-minute Walking Distance (6MWD) at Week 24 | This test assessed the distance a patient could walk in 6 minutes (Rutkove et al 2002). If the patient was not able to walk for 6 minutes then a 2 minute walking test was conducted | Pharmacodynamic (PD) included patients with PD data and no major protocol deviations | Posted | Mean | Standard Deviation | meters | Baseline, 24 weeks |
|
|
|
| Secondary | BAF312 Trough Plasma Concentrations (PK Set) | All blood samples were taken by either direct venipuncture or an indwelling cannula inserted in a forearm vein. For each sample, approximately 2 mL of blood was drawn. BAF312 was determined in ethylenediaminetetraacetic acid (EDTA) plasma using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical method for the quantification. The anticipated lower limit of quantification (LLOQ) was 0.02 ng/mL using 0.1 mL of plasma | P | Posted | Mean | Standard Deviation | ng/mL | -7 Baseline, day 28, 56, 84 |
|
|
|
| 1 |
| 7 |
| 6 |
| 7 |
| EG001 | Period 1 BAF312 10mg | Period 1 BAF312 10mg | 0 | 2 | 2 | 2 |
| EG002 | Period 1 Placebo | Period 1 Placebo | 0 | 5 | 4 | 5 |
| EG003 | Period 2 BAF312 2mg/ BAF312 2mg | Period 2 BAF312 2mg/ BAF312 2mg | 0 | 6 | 4 | 6 |
| EG004 | Period 2 Placebo/ BAF312 2mg | Period 2 Placebo/ BAF312 2mg | 0 | 3 | 2 | 3 |
| Haemolytic uraemic syndrome | Blood and lymphatic system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA (19.0) | Systematic Assessment |
|
| Cataract | Eye disorders | MedDRA (19.0) | Systematic Assessment |
|
| Eye pain | Eye disorders | MedDRA (19.0) | Systematic Assessment |
|
| Ocular hyperaemia | Eye disorders | MedDRA (19.0) | Systematic Assessment |
|
| Vitreous detachment | Eye disorders | MedDRA (19.0) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
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| Asthenia | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA (19.0) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (19.0) | Systematic Assessment |
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| Feeling cold | General disorders | MedDRA (19.0) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (19.0) | Systematic Assessment |
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| Cholelithiasis | Hepatobiliary disorders | MedDRA (19.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Epicondylitis | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Carbon monoxide diffusing capacity decreased | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Cardiac murmur | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA (19.0) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
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| Polymyositis | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Cerebral artery stenosis | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA (19.0) | Systematic Assessment |
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| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA (19.0) | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Papule | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
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| Day 28 |
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| Day 56 |
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| Day 84 |
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