Efficacy and Tolerability of BAF312 in Patients With Polymyositis

A Multi-centre Double-blind, Placebo Controlled, Proof of Concept Study to Evaluate the Efficacy and Tolerability of BAF312 in Patients With Polymyositis

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).

Study Overview

• Status: Terminated
• Conditions: Polymyositis
• Intervention / Treatment: Drug: Placebo; Drug: BAF312

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Torono, Ontario, Canada, M5G 2C4
      • Novartis Investigative Site
• Czechia
  • Prague 2, Czechia, 128 50
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1083
    • Novartis Investigative Site
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
• Poland
  • Bydgoszcz, Poland, 85-168
    • Novartis Investigative Site
• Taiwan
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
  • Taichung, Taiwan, 40705
    • Novartis Investigative Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• "definite" or "probable" for polymyositis at least three months before Baseline
• active disease as defined by elevated CK levels, or other enzymes, or MRI/biopsy if enzymes are normal, and persisting muscle weakness
• stable dose of corticosteroid for at least 2 weeks prior to Baseline and should not have received a medium or high dose in the last 8 weeks prior to study entry.
• patients treated with methotrexate must have been on a stable dose for at least 6 weeks prior to Baseline.

Exclusion Criteria:

• Patients with overlap polymyositis, late-stage polymyositis, or other types of myositis.
• Preexisting severe cardiac or pulmonary involvement, malignancy of any organ system or significant eye diseases.
• Uncontrolled diabetes mellitus or diabetes complicated with organ involvement.
• Pregnant or nursing (lactating) women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 5 placebo tablets daily during non-titration phase	Drug: Placebo; Matching placebo tablet for oral administration
Experimental: BAF312 2mg; 1 tablet of BAF312 2 mg + 4 tablets of Placebo daily during non-titration phase	Drug: BAF312; BAF312 in 4 dosage strengths in tablet form: 0.25 mg, 0.5 mg, 1 mg, 2 mg for oral administration
Experimental: BAF312 10 mg; 5 tablets of BAF312 2 mg daily during non-titration phase	Drug: BAF312; BAF312 in 4 dosage strengths in tablet form: 0.25 mg, 0.5 mg, 1 mg, 2 mg for oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2013
• Primary Completion (Actual): August 5, 2016
• Study Completion (Actual): August 5, 2016

Study Registration Dates

• First Submitted: February 1, 2013
• First Submitted That Met QC Criteria: February 27, 2013
• First Posted (Estimate): March 1, 2013

Study Record Updates

• Last Update Posted (Actual): January 5, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Myositis; Polymyositis; inflammatory myopathy; PM; chronic muscle inflammation; inclusion body myositis
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Myositis; Polymyositis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Sphingosine 1 Phosphate Receptor Modulators; Siponimod
• Other Study ID Numbers: CBAF312X2205

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No