Study of efficacy and tolerability for BAF312 compared to placebo in patients with polymyositis

• Register: EUCTR
• Last refreshed on: 21 November 2016
• Main ID: EUCTR2012-002859-42-HU
• Date of registration: 05/11/2012
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Study of efficacy and tolerability for BAF312 compared to placebo in patients with polymyositis
• Scientific title: A multi-centre, double-blind, placebo controlled, proof of concept study to evaluate the efficacy and tolerability of BAF312 in patients with polymyositis
• Date of first enrolment: 25/01/2013
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002859-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, Czech Republic, Hungary, Poland, United States

Contacts

• Name: Public Information Desk
• Affiliation: Novartis Hungária Kft., Pharma

• Name: Public Information Desk
• Affiliation: Novartis Hungária Kft., Pharma

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects eligible for inclusion in this study have to fulfill all of the following criteria:
1. Written informed consent must be obtained before any assessment is performed
2. Male and female patients between 18 - 75 (inclusive) years of age who have been defined as "definite" or “probable” based on the criteria of Bohan and Peter (Bohan and Peter 1975) for polymyositis at least three months before Baseline. Patients must have a history of muscle inflammation documented through objective evidence in at least one of EMG, MRI or biopsy
3. At screening, and baseline, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position after the subject has rested for at least three minutes. Sitting vital signs should be within the following ranges:
- oral body temperature between 35.0-37.5 °C
- systolic blood pressure, 90-140 mm Hg
- diastolic blood pressure, 50-90 mm Hg
- pulse rate, 50 - 90 bpm
4. Able to communicate well with the investigator, to understand and comply with the requirements of the study
5. Patients must have active disease as defined by CK levels elevated to at least 1.3-fold of the ULN. Such elevated CK levels must be demonstrated at least twice between Screening and Baseline (inclusive)
6. Patients must demonstrate persisting muscle weakness defined as having a score no greater than 135/150 on the Baseline manual muscle testing (maximum MMT-8 score of 150)
7. Patients must have received (but inadequately responding to) standard therapies as defined by corticosteroid alone or in combination with second line immunosuppressive agents
such as methotrexate, azathioprine, cyclosporine A or mycophenolate for at least three months before Baseline
8. Patients must be on a stable dose of corticosteroid (5-20 mg prednisone or equivalent per day) for at least 2 weeks prior to Baseline and should not have received a medium or high dose (= 100 mg prednisone or equivalent per day) corticosteroid therapy in the last 8 weeks prior to study entry
9. Patients currently treated with oral or subcutaneous methotrexate must have been on a stable dose of no more than 25 mg per week for at least 6 weeks prior to Baseline. Concomitant methotrexate therapy is permitted but not mandatory for patients to enter the study
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 27
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion criteria:
Subjects fulfilling any of the following criteria are not eligible for inclusion in this study:
1. Use of other investigational drugs (other than BAF312)- see protocol
2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
3. Polymyositis patients having
a. overlap polymyositis (see protocol)
b. preexisting severe cardiac or pulmonary involvement or any major internal organ damage which deemed by the Investigator to be clinically significant
c. late-stage polymyositis whose muscle weakness, according to the Investigator, could be attributable to muscle damage rather than to myositis disease activity
4. Patients with other types of myositis or myopathies including:
a. dermatomyositis. PM patients with sign of overlapping PM and DM (e.g. based on histology) but with no typical DM skin lesions may be eligible at the investigator`s discretion
b. paraneoplastic polymyositis
c. inclusion body myositis
d. necrotizing myopathy
e. any myopathy due to conditions other than PM
5. Patients who have been treated with other therapies as defined in the protocol
6. Patients with concurrent or history of macular edema or any significant eye disease that increases the risk of macular edema
7. Any of the following cardiovascular conditions:
a. History of or current significant cardiac disease including cardiac failure (NYHA functional class II-IV), myocarditis, cardiomyopathy, angina pectoris or myocardial infarction (within 12 months), or uncontrolled arterial hypertension.
b. Cardiac conduction or rhythm disorders including complete left bundle branch block, sinus arrest or sino-atrial block, symptomatic bradycardia, sick sinus syndrome,Mobitz Type II second degree AV-block or high grade AV-block (either history or observed at screening),
c. Cardiac arrhythmias requiring treatment or ablation (either history or observed at screening), or a history of cardiac syncope.
d. Patients receiving current treatment with Class Ia or III antiarrhythmic drugs
e. Conditions requiring treatment with medication that may cause AV block and suppress AV conduction (e.g. beta-blockers, carbamazepine, lamotrigine, nondihydropyridine
calcium-channel blockers, or cardiac glycosides)PR interval >230 msec. Long QT syndrome or QTcF prolongation >450 msec in males or >470 msec in females, on screening electrocardiogram (ECG)
f. Severe autonomic nervous system dysfunction
g. Catheter ablation
8. Certain pulmonary conditions (see protocol)
9. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
10. Uncontrolled diabetes mellitus or diabetes complicated with organ involvement such as diabetic nephropathy or retinopathy.
11. Active systemic bacterial, viral or fungal infections, or diagnosis of AIDS, Hepatitis B, Hepatitis C infection.
12. Evidence of any other acute or chronic infectious diseases.
13. Negative for varicella-zoster virus IgG antibodies at Screening.
14. Have received any live or live attenuated vaccines (including for varicella-zoster virus or measles) within 2 months prior to randomization.
15. Homozygosity for CYP2C9*3 (will be tested at Screening), and/or refusal to test for CYP2C9*3 haplotype.
16. Patients using (or having recently used) concomitant medications that are strong or moderate inducers of CYP2C9.
17. Evid

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Polymyositis
MedDRA version: 14.1 Level: PT Classification code 10036102 Term: Polymyositis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Product Name: BAF312 0.25 mg tablet
Product Code: BAF312X
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Siponimid
CAS Number: 1234627-85-0
Current Sponsor code: BAF312
Other descriptive name: BAF312 hemifumarate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: BAF312 1 mg tablet
Product Code: BAF312X
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Siponimod
CAS Number: 1234627-85-0
Current Sponsor code: BAF312
Other descriptive name: BAF312 hemifumarate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To assess the clinical effect of 2 mg BAF312 once daily in patients with PM over 12 weeks using both manual muscle testing (MMT-8) and serum creatine kinase (CK) as a combined endpoint

Timepoint(s) of evaluation of this end point: Baseline, over 12 weeks

Primary end point(s): manual muscle testing (MMT) and serum CK levels

Secondary Objective: - To assess the safety and tolerability of BAF312 in patients with PM
- To characterize the steady state pharmacokinetics of BAF312 in patients with PM

Further objectives see protocol

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Baseline, over 12 weeks

Secondary end point(s): IMACS, 6 minutes walking distance (6MWD) test, Timed “up and go” (TUG) test

Secondary ID(s)

CBAF312X2205

Source(s) of Monetary Support

Novartis Pharma AG