Efficacy and Tolerability of BAF312 in Patients With Polymyositis

Polymyositis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01801917
• Other study ID #: CBAF312X2205
• Status: Terminated
• Phase: Phase 2
• Start date: April 24, 2013
• Est. completion date: August 5, 2016

Study information

• Verified date: January 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: August 5, 2016
• Est. primary completion date: August 5, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Polymyositis

Intervention

Drug:
• Placebo
Matching placebo tablet for oral administration
• BAF312
BAF312 in 4 dosage strengths in tablet form: 0.25 mg, 0.5 mg, 1 mg, 2 mg for oral administration

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Torono	Ontario
Czechia	Novartis Investigative Site	Prague 2
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Poland	Novartis Investigative Site	Bydgoszcz
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taichung
United States	Novartis Investigative Site	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Hungary,  Poland,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline, at 12 weeks
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	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	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	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	-7 Baseline, day 28, 56, 84

External Links

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