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Efficacy and Tolerability of BAF312 in Patients With Polymyositis

Primary Purpose

Polymyositis

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
BAF312
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polymyositis focused on measuring Polymyositis, Myositis, PM, chronic muscle inflammation, inflammatory myopathy, inclusion body myositis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Placebo

BAF312 2mg

BAF312 10 mg

Arm Description

5 placebo tablets daily during non-titration phase

1 tablet of BAF312 2 mg + 4 tablets of Placebo daily during non-titration phase

5 tablets of BAF312 2 mg daily during non-titration phase

Outcomes

Primary Outcome Measures

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.
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

Secondary Outcome Measures

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
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
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

Full Information

First Posted
February 1, 2013
Last Updated
December 9, 2020
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01801917
Brief Title
Efficacy and Tolerability of BAF312 in Patients With Polymyositis
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Terminated
Study Start Date
April 24, 2013 (Actual)
Primary Completion Date
August 5, 2016 (Actual)
Study Completion Date
August 5, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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).
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polymyositis
Keywords
Polymyositis, Myositis, PM, chronic muscle inflammation, inflammatory myopathy, inclusion body myositis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
5 placebo tablets daily during non-titration phase
Arm Title
BAF312 2mg
Arm Type
Experimental
Arm Description
1 tablet of BAF312 2 mg + 4 tablets of Placebo daily during non-titration phase
Arm Title
BAF312 10 mg
Arm Type
Experimental
Arm Description
5 tablets of BAF312 2 mg daily during non-titration phase
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo tablet for oral administration
Intervention Type
Drug
Intervention Name(s)
BAF312
Intervention Description
BAF312 in 4 dosage strengths in tablet form: 0.25 mg, 0.5 mg, 1 mg, 2 mg for oral administration
Primary Outcome Measure Information:
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)
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
Title
Percent Change From Baseline at Week 12 for BAF312 2 mg, 10 mg or Placebo (Once Daily) Serum Creatine Kinase (CK) Levels
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
Secondary Outcome Measure Information:
Title
Six-minute Walking Distance (6MWD) at Week 12
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
Title
Six-minute Walking Distance (6MWD) at Week 24
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
Title
BAF312 Trough Plasma Concentrations (PK Set)
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
Novartis Investigative Site
City
Torono
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
Novartis Investigative Site
City
Prague 2
ZIP/Postal Code
128 50
Country
Czechia
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Novartis Investigative Site
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Novartis Investigative Site
City
Bydgoszcz
ZIP/Postal Code
85-168
Country
Poland
Facility Name
Novartis Investigative Site
City
Taichung
ZIP/Postal Code
40447
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taichung
ZIP/Postal Code
40705
Country
Taiwan

12. IPD Sharing Statement

Links:
URL
https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=225
Description
A Plain Language Trial Summary is available on novartisclinicaltrials.com

Learn more about this trial

Efficacy and Tolerability of BAF312 in Patients With Polymyositis

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