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Trial record 19 of 85 for:    Polymyositis AND Myopathy

Efficacy and Tolerability of BAF312 in Patients With Polymyositis

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ClinicalTrials.gov Identifier: NCT01801917
Recruitment Status : Terminated
First Posted : March 1, 2013
Results First Posted : January 4, 2018
Last Update Posted : January 4, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Polymyositis
Interventions Drug: Placebo
Drug: BAF312
Enrollment 14
Recruitment Details  
Pre-assignment Details  
Arm/Group Title BAF312 2mg/BAF312 2mg BAF312 10 mg/BAF312 10 mg Placebo/BAF312 2 mg Placebo/BAF312 10 mg
Hide Arm/Group Description Patients in Period 1 continue on same 2 mg dose of BAF312 in Period 2 Patients in Period 1 continue on same 10 mg dose of BAF312 in Period 2 Patients on placebo in Period 1 switch to active 2 mg BAF312 in Period 2 Patients on placebo in Period 1 switch to active 10 mg BAF312 in Period 2
Period Title: Period 1 - Randomized
Started 7 2 4 1
Completed 6 2 3 1
Not Completed 1 0 1 0
Reason Not Completed
Adverse Event             1             0             1             0
Period Title: Extension - All Active
Started 6 0 3 0
Completed 6 0 3 0
Not Completed 0 0 0 0
Arm/Group Title BAF312 2mg/BAF312 2mg BAF312 10 mg/BAF312 10 mg Placebo/BAF312 2 mg Placebo/BAF312 10 mg Total
Hide Arm/Group Description Patients in Period 1 continue on same 2 mg dose of BAF312 in Period 2 Patients in Period 1 continue on same 10 mg dose of BAF312 in Period 2 Patients on placebo in Period 1 switch to active 2 mg BAF312 in Period 2 Patients on placebo in Period 1 switch to active 10 mg BAF312 in Period 2 Total of all reporting groups
Overall Number of Baseline Participants 7 2 4 1 14
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants 2 participants 4 participants 1 participants 14 participants
50.3  (14.78) 47.0  (21.21) 48.0  (8.83) 53.0  (0.0) 49.4  (12.51)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 2 participants 4 participants 1 participants 14 participants
Female
5
  71.4%
2
 100.0%
2
  50.0%
1
 100.0%
10
  71.4%
Male
2
  28.6%
0
   0.0%
2
  50.0%
0
   0.0%
4
  28.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 7 participants 2 participants 4 participants 1 participants 14 participants
Caucasian 7 1 3 0 11
Black 0 0 0 1 1
Asian 0 1 1 0 2
Disease duration  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants 2 participants 4 participants 1 participants 14 participants
5.6  (4.46) 5.4  (2.74) 2.7  (1.67) 16.9  (0) 5.6  (4.77)
Baseline MMT24 Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 7 participants 2 participants 4 participants 1 participants 14 participants
202.6  (41.74) 184.0  (19.80) 189.5  (45.65) 166.0  (0) 193.6  (37.90)
[1]
Measure Description: Manual muscle testing in 24 muscle groups (MMT24). The scores range was 0 to 260. Higher scores indicate better outcome.
Taking DMARD at baseline   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 7 participants 2 participants 4 participants 1 participants 14 participants
7 2 4 1 14
[1]
Measure Description: Taking a disease-modifying antirheumatic drugs
1.Primary Outcome
Title 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)
Hide Description 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.
Time Frame Baseline, at 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) included patients with PD data and no major protocol deviations
Arm/Group Title BAF312 2mg BAF312 10 mg Placebo
Hide Arm/Group Description:
1 tablet of BAF312 2 mg + 4 tablets of Placebo daily during Period 1
5 tablets of BAF312 2 mg daily during Period 1
matching placebo
Overall Number of Participants Analyzed 7 2 5
Mean (90% Confidence Interval)
Unit of Measure: scores on a scale
11.2
(3.5 to 19.2)
39.0
(10.7 to 67.2)
9.1
(-1.6 to 20.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BAF312 2mg, Placebo
Comments It was a Bayesian analysis with non-informative prior for co-primary endpoints, MMT-24 and CK, with dual criteria for statistical significance: ≥ 90% posterior probability (PP) of achieving an increase from baseline in MMT24 and decrease in CK and clinical relevance: ≥ 50% PP achieving an increase of 15 points in MMT24 and a decrease of 30% in CK vs. placebo. For this table the value is the posterior probability of achieving an increase in MMT24 and a decrease in CK in 2mg group vs. placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Bayesian
Estimated Value 0.586
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BAF312 2mg, Placebo
Comments It was a Bayesian analysis with non-informative prior for co-primary endpoints, MMT-24 and CK, with dual criteria for statistical significance: ≥ 90% posterior probability (PP) of achieving an increase from baseline in MMT24 and decrease in CK and clinical relevance: ≥ 50% PP achieving an increase of 15 points in MMT24 and a decrease of 30% in CK vs. placebo. . For this table the value is the PP of achieving an increase of 15 points in MMT24 and a decrease of 30% in CK in 2mg group vs. placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Bayesian
Estimated Value 0.022
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BAF312 10 mg, Placebo
Comments It was a Bayesian analysis with non-informative prior for co-primary endpoints, MMT-24 and CK, with dual criteria for statistical significance: ≥ 90% posterior probability (PP) of achieving an increase from baseline in MMT24 and decrease in CK and clinical relevance: ≥ 50% PP achieving an increase of 15 points in MMT24 and a decrease of 30% in CK vs. placebo. For this table the value is the posterior probability of achieving an increase in MMT24 and a decrease in CK in 10mg group vs. placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Bayesian
Estimated Value 0.963
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BAF312 10 mg, Placebo
Comments It was a Bayesian analysis with non-informative prior for co-primary endpoints, MMT-24 and CK, with dual criteria for statistical significance: ≥ 90% posterior probability (PP) of achieving an increase from baseline in MMT24 and decrease in CK and clinical relevance: ≥ 50% PP achieving an increase of 15 points in MMT24 and a decrease of 30% in CK vs. placebo. . For this table the value is the PP of achieving an increase of 15 points in MMT24 and a decrease of 30% in CK in 10mg group vs. placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Bayesian
Estimated Value 0.837
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percent Change From Baseline at Week 12 for BAF312 2 mg, 10 mg or Placebo (Once Daily) Serum Creatine Kinase (CK) Levels
Hide Description 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
Time Frame Baseline, at 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) included patients with PD data and no major protocol deviations
Arm/Group Title BAF312 2mg BAF312 10 mg Placebo
Hide Arm/Group Description:
1 tablet of BAF312 2 mg + 4 tablets of Placebo daily during Period 1
5 tablets of BAF312 2 mg daily during Period 1
matching placebo
Overall Number of Participants Analyzed 7 2 5
Mean (90% Confidence Interval)
Unit of Measure: U/L
-19.7
(-32.3 to -4.7)
-55.6
(-77.1 to -13.5)
-0.5
(-21.8 to 25.9)
3.Secondary Outcome
Title Six-minute Walking Distance (6MWD) at Week 12
Hide Description 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
Time Frame Baseline, 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) included patients with PD data and no major protocol deviations
Arm/Group Title BAF312 2mg BAF312 10 mg Placebo
Hide Arm/Group Description:
1 tablet of BAF312 2 mg + 4 tablets of Placebo daily during Period 1
5 tablets of BAF312 2 mg daily during Period 1
matching placebo
Overall Number of Participants Analyzed 6 1 4
Mean (Standard Deviation)
Unit of Measure: meters
Period 1, Week 12 362.47  (52.02) 393.00  (0.0) 303.10  (112.480)
Distance walked,change from BL at Wk 12 46.82  (65.64) 23.00  (0.0) -6.40  (21.981)
4.Secondary Outcome
Title Six-minute Walking Distance (6MWD) at Week 24
Hide Description 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
Time Frame Baseline, 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) included patients with PD data and no major protocol deviations
Arm/Group Title BAF312 2mg Placebo/BAF312 2 mg
Hide Arm/Group Description:
1 tablet of BAF312 2 mg + 4 tablets of Placebo daily during Period 1
Patients on placebo in Period 1 switch to active 2 mg BAF312 in Period 2
Overall Number of Participants Analyzed 6 3
Mean (Standard Deviation)
Unit of Measure: meters
Period 2, Week 24 364.60  (73.803) 329.33  (186.551)
Distance walked,change from baseline at Wk 24 48.95  (91.922) 4.33  (51.637)
5.Secondary Outcome
Title BAF312 Trough Plasma Concentrations (PK Set)
Hide Description 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
Time Frame -7 Baseline, day 28, 56, 84
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
P
Arm/Group Title BAF312 2mg BAF312 10 mg
Hide Arm/Group Description:
1 tablet of BAF312 2 mg + 4 tablets of Placebo daily during Period 1
5 tablets of BAF312 2 mg daily during Period 1
Overall Number of Participants Analyzed 6 2
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day - 7 Number Analyzed 6 participants 2 participants
0  (0) 0  (0)
Day 28 Number Analyzed 6 participants 1 participants
25.3  (11.2) 182  (0)
Day 56 Number Analyzed 5 participants 1 participants
25.1  (12.6) 270  (0)
Day 84 Number Analyzed 6 participants 1 participants
21.4  (10.1) 240  (0)
Time Frame 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.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Period 1 BAF312 2mg Period 1 BAF312 10mg Period 1 Placebo Period 2 BAF312 2mg/ BAF312 2mg Period 2 Placebo/ BAF312 2mg
Hide Arm/Group Description Period 1 BAF312 2mg Period 1 BAF312 10mg Period 1 Placebo Period 2 BAF312 2mg/ BAF312 2mg Period 2 Placebo/ BAF312 2mg
All-Cause Mortality
Period 1 BAF312 2mg Period 1 BAF312 10mg Period 1 Placebo Period 2 BAF312 2mg/ BAF312 2mg Period 2 Placebo/ BAF312 2mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Period 1 BAF312 2mg Period 1 BAF312 10mg Period 1 Placebo Period 2 BAF312 2mg/ BAF312 2mg Period 2 Placebo/ BAF312 2mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/7 (14.29%)   0/2 (0.00%)   0/5 (0.00%)   0/6 (0.00%)   0/3 (0.00%) 
Blood and lymphatic system disorders           
Haemolytic anaemia  1  1/7 (14.29%)  0/2 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/3 (0.00%) 
Haemolytic uraemic syndrome  1  1/7 (14.29%)  0/2 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/3 (0.00%) 
Renal and urinary disorders           
Acute kidney injury  1  1/7 (14.29%)  0/2 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/3 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (19.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Period 1 BAF312 2mg Period 1 BAF312 10mg Period 1 Placebo Period 2 BAF312 2mg/ BAF312 2mg Period 2 Placebo/ BAF312 2mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/7 (85.71%)   2/2 (100.00%)   4/5 (80.00%)   4/6 (66.67%)   2/3 (66.67%) 
Cardiac disorders           
Palpitations  1  0/7 (0.00%)  0/2 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  0/3 (0.00%) 
Eye disorders           
Cataract  1  1/7 (14.29%)  0/2 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/3 (33.33%) 
Eye pain  1  0/7 (0.00%)  1/2 (50.00%)  0/5 (0.00%)  0/6 (0.00%)  0/3 (0.00%) 
Ocular hyperaemia  1  1/7 (14.29%)  0/2 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/3 (0.00%) 
Vitreous detachment  1  0/7 (0.00%)  0/2 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/3 (0.00%) 
Gastrointestinal disorders           
Abdominal pain upper  1  1/7 (14.29%)  0/2 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  0/3 (0.00%) 
Diarrhoea  1  1/7 (14.29%)  0/2 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/3 (33.33%) 
Nausea  1  1/7 (14.29%)  0/2 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  0/3 (0.00%) 
Vomiting  1  0/7 (0.00%)  1/2 (50.00%)  0/5 (0.00%)  0/6 (0.00%)  0/3 (0.00%) 
General disorders           
Asthenia  1  1/7 (14.29%)  0/2 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/3 (0.00%) 
Chest discomfort  1  0/7 (0.00%)  1/2 (50.00%)  0/5 (0.00%)  0/6 (0.00%)  0/3 (0.00%) 
Fatigue  1  0/7 (0.00%)  0/2 (0.00%)  1/5 (20.00%)  1/6 (16.67%)  0/3 (0.00%) 
Feeling cold  1  1/7 (14.29%)  0/2 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/3 (0.00%) 
Pyrexia  1  1/7 (14.29%)  0/2 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/3 (0.00%) 
Hepatobiliary disorders           
Cholelithiasis  1  0/7 (0.00%)  0/2 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/3 (0.00%) 
Infections and infestations           
Nasopharyngitis  1  0/7 (0.00%)  0/2 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  0/3 (0.00%) 
Upper respiratory tract infection  1  0/7 (0.00%)  0/2 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  1/3 (33.33%) 
Urinary tract infection  1  0/7 (0.00%)  1/2 (50.00%)  0/5 (0.00%)  0/6 (0.00%)  0/3 (0.00%) 
Injury, poisoning and procedural complications           
Epicondylitis  1  0/7 (0.00%)  0/2 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  0/3 (0.00%) 
Investigations           
Carbon monoxide diffusing capacity decreased  1  0/7 (0.00%)  0/2 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  0/3 (0.00%) 
Cardiac murmur  1  1/7 (14.29%)  0/2 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/3 (0.00%) 
Gamma-glutamyltransferase increased  1  0/7 (0.00%)  0/2 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/3 (33.33%) 
Musculoskeletal and connective tissue disorders           
Back pain  1  1/7 (14.29%)  0/2 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/3 (0.00%) 
Musculoskeletal pain  1  0/7 (0.00%)  0/2 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/3 (0.00%) 
Myalgia  1  1/7 (14.29%)  0/2 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/3 (0.00%) 
Pain in extremity  1  0/7 (0.00%)  0/2 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/3 (0.00%) 
Polymyositis  1  0/7 (0.00%)  0/2 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/3 (33.33%) 
Spinal pain  1  0/7 (0.00%)  0/2 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/3 (0.00%) 
Nervous system disorders           
Cerebral artery stenosis  1  0/7 (0.00%)  0/2 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  0/3 (0.00%) 
Dizziness  1  0/7 (0.00%)  1/2 (50.00%)  2/5 (40.00%)  0/6 (0.00%)  0/3 (0.00%) 
Headache  1  2/7 (28.57%)  0/2 (0.00%)  2/5 (40.00%)  0/6 (0.00%)  0/3 (0.00%) 
Psychiatric disorders           
Depression  1  1/7 (14.29%)  0/2 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/3 (0.00%) 
Reproductive system and breast disorders           
Benign prostatic hyperplasia  1  1/7 (14.29%)  0/2 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/3 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Rhinorrhoea  1  1/7 (14.29%)  0/2 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/3 (0.00%) 
Skin and subcutaneous tissue disorders           
Papule  1  0/7 (0.00%)  0/2 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/3 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (19.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01801917     History of Changes
Other Study ID Numbers: CBAF312X2205
First Submitted: February 1, 2013
First Posted: March 1, 2013
Results First Submitted: August 1, 2017
Results First Posted: January 4, 2018
Last Update Posted: January 4, 2018