Study of efficacy and tolerability for BAF312 compared to placebo in patients with active dermatomyositis.

• Register: EUCTR
• Last refreshed on: 11 April 2016
• Main ID: EUCTR2013-001799-39-CZ
• Date of registration: 08/10/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Study of efficacy and tolerability for BAF312 compared to placebo in patients with active dermatomyositis.
• Scientific title: A double blind, randomized, placebo-controlled study to evaluate, safety, tolerability, efficacy and preliminary dose-response of BAF312 in patients with active dermatomyositis.
• Date of first enrolment: 19/12/2013
• Target sample size: 56
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001799-39
• 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: 4

Countries of recruitment

Canada, Czech Republic, Germany, Hungary, Japan, Poland, United States

Contacts

• Name: Informacní služba – klin. hodnocení
• Affiliation: Novartis s.r.o.

• Name: Informacní služba – klin. hodnocení
• Affiliation: Novartis s.r.o.

Key inclusion & exclusion criteria

Inclusion criteria:
• Written informed consent must be obtained before any assessment is performed.
• Patients who have been defined as "definite" or “probable” based on the criteria of Bohan and Peter (Bohan and Peter 1975) for dermatomyositis at least 3 months before screening
• Patients must have active disease as defined by muscle weakness
• Patients must have responded inadequately to previous standard of care or have demonstrated significant toxicity or intolerance to such therapies.
• Patients may be on a stable dose of corticosteroid (up/equal to 20 mg once daily prednisone equivalent)
• Patients currently treated with oral or subcutaneous MTX must have been a stable dose of no more/equal to than 25 mg per week
• Patients currently treated with Azathioprine must have been a stable maintenance dose of no more/equal to 3 mg/kg/day
• Negative cancer screening conducted in the 12 months prior to screening visit

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 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion criteria:
• Dermatomyositis patients having overlap myositis or any other type of myositis including paraneoplastic myositis, drug-induced myopathy, necrotizing myositis
• Preexisting severe cardiac or pulmonary conditions, malignancy of any organ system or significant eye diseases.
• Uncontrolled diabetes mellitus or diabetes complicated with organ involvement.
• Pregnant or nursing (lactating) women
• Other protocol-defined inclusion/exclusion criteria apply.



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

Health Condition(s) or Problem(s) studied

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

Active dermatomyositis
MedDRA version: 18.1 Level: PT Classification code 10012503 Term: Dermatomyositis System Organ Class: 10040785 - Skin and subcutaneous tissue disorders

Intervention(s)

Product Code: BAF312 0.25 mg
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: 0.25-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Code: BAF312 0.5 mg
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: 0.5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Code: BAF312 1 mg
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

Product Code: BAF312 2 mg
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: 2-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To assess the effects of different doses of BAF312 on safety, pharmacokinetics and peripheral blood lymphocyte counts in active DM patients

To assess the efficacy of different doses of BAF312 after 3 months of treatment in active DM patients as assessed by manual muscle testing using the MMT-8 scoring system

Primary end point(s): Manual Muscle Testing - 24 muscles (MMT-24). Efficacy of BAF312 will be assessed by comparing the improvements with every dose of BAF312 to that of placebo

Timepoint(s) of evaluation of this end point: 6 months

Main Objective: The primary aim of this study is to assess the efficacy of different doses of BAF312 on the MMT-24 after 6 months.
The overall efficacy of BAF312 will be assessed by comparing the improvements of MMT-24 with every dose of BAF312 to that of placebo. Then the dose response curve of MMT-24 will be estimated with the aim to determine a target dose for
the program.

Secondary Outcome(s)

Secondary end point(s): • Adverse Events. All information obtained on adverse events will be displayed by treatment (dose group) and subject. Secondary variables include the incidence of adverse events.
• Pharmacokinetics. BAF312 plasma concentration data will be listed by treatment (dose group), subject and visit/sampling time point. Descriptive summary statistics will be provided by treatment and visit/sampling time point.
Secondary variables include plasma BAF312 concentrations.
• Peripheral blood lymphocyte counts. Absolute lymphocyte counts will be plotted against time by dose level.
Secondary variables include peripheral blood lymphocyte counts.
• Manual Muscle Testing - 24 muscles (MMT-24). Efficacy of BAF312 will be assessed by comparing the improvements with every dose of BAF312 to that of placebo.
Changes from baseline in MMT-24 at 3 months will also be evaluated.
The dose-response will be assessed in the same way as for the 6-month data.
• 6 Minutes Walking Distance test. Efficacy of BAF312 will be assessed by comparing the changes in walking distance across all doses of BAF312 to that of placebo
Changes from baseline in 6 Minute walking distance at 6 months of
treatment will be assessed.

Timepoint(s) of evaluation of this end point: For Manual Muscle Testing : 3 months
For all others: 6 months

Secondary ID(s)

NCT02029274

2013-001799-39-HU

CBAF312X2206

Source(s) of Monetary Support

Novartis Pharma Services AG