Efficacy and Tolerability of BAF312 in Patients With Polymyositis

Phase 2TerminatedNCT01801917

Novartis Pharmaceuticals14 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Polymyositis

Interventions

PlaceboDRUG

Matching placebo tablet for oral administration

BAF312DRUG

BAF312 in 4 dosage strengths in tablet form: 0.25 mg, 0.5 mg, 1 mg, 2 mg for oral administration

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (8)

Novartis Investigative Site

Phoenix, Arizona, United States

Novartis Investigative Site

Torono, Ontario, Canada

Novartis Investigative Site

Prague, Czechia

Novartis Investigative Site

Budapest, Hungary

Outcomes

Primary Outcomes

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.

Time frame: 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

Time frame: Baseline, at 12 weeks

Secondary Outcomes

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

Time frame: 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

Time frame: 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

Data from ClinicalTrials.gov

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