An extension study to the CBAF312A2201 study to evaluate long-term safety, tolerability and efficacy of BAF312 given orally once daily in patients with multiple sclerosis with relapses

• Register: EUCTR
• Last refreshed on: 9 January 2017
• Main ID: EUCTR2009-014392-51-HU
• Date of registration: 02/11/2009
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: An extension study to the CBAF312A2201 study to evaluate long-term safety, tolerability and efficacy of BAF312 given orally once daily in patients with multiple sclerosis with relapses
• Scientific title: An extension study to the CBAF312A2201 study to evaluate long-term safety, tolerability and efficacy of BAF312 given orally once daily in patients with relapsing multiple sclerosis
• Date of first enrolment: 02/09/2010
• Target sample size: 275
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-014392-51
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Finland, Germany, Hungary, Italy, Poland, Russian Federation, Spain, Turkey, United States

Contacts

• Name: Public Information Desk
• Affiliation: Novartis Hungary Kft. Pharma

• Name: Public Information Desk
• Affiliation: Novartis Hungary Kft. Pharma

Key inclusion & exclusion criteria

Inclusion criteria:
1.Patients completed the core study CBAF312A2201
2.Written informed consent provided before any assessment of the extension study
3.Female patients at risk of becoming pregnant must have a negative pregnancy test and use simultaneously two forms of effective contraception during dosing and for 30 days after the
last dose of BAF312.

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 275
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.Premature discontinuation of the study drug during the core study due to occurrence of discontinuation withdrawal criteria or due to non-compliance.
2.Newly diagnosed systemic disease other than MS which may require immunosuppressive treatment
3.Presence of malignancy (except for successfully-treated basal or squamous cell carcinoma of skin)
4.Diagnosis of macular edema. Patients with ME history are allowed to enter into the extension phase if ME did not occur during the core study or at the Screening visit for the extension
5.Newly diagnosed diabetes mellitus or a blood glucose obtained suspicious for diabetes
6.Active systemic bacterial, viral or fungal infections, or known to have AIDS, defined as a positive HIV antibody test, Hepatitis B, Hepatitis C infection, defined as Hepatitis B surface antigen or Hepatitis antibody tests, respectively, or having a positive referring laboratory test
7.Any medically unstable condition, as assessed by the treating physician
8.Any of the following CV conditions:
•history or presence of stable or unstable IHD, MI, myocarditis or cardiomyopathy;
•cardiac failure (NYHA Class II-IV) or any severe cardiac disease
•history or presence of symptomatic arrhythmia requiring current treatment or being otherwise of clinical significance
•history or presence of a clinically relevant impairment of cardiay conduction including sick sinus syndrome, sino-atrial heart block
•clinically significant AV block, bundle branch block or an increased QTc interval > 440 msec on screening electrocardiogram (ECG) prior to enrollment
•arterial hypertension, uncontrolled by medication
•newly diagnosed Raynaud’s syndrome
•history of symptomatic bradycardia
•required treatment with medication that impairs cardiac conduction with the exception of beta-blockers (Section 5.5.7) (e.g., beta blockers, verapamil-type and diltiazem-type calcium-channel blockers, or cardiac glycosides)
•history of syncope of suspected cardiac origin
•history of catheter ablation
9.Any of the following pulmonary conditions:
•Severe respiratory disease or pulmonary fibrosis diagnosed during the core study
•TB, except for history of successfully treated TB or history of prophylactic treatment after positive PPD skin reaction
•Abnormal chest x-ray or HRCT suggestive of active pulmonary disease in the core study or at screening (if appropriate) in the extension
•Abnormal pulmonary function tests: FEV1 or FVC values lowed than 70% of predicted value
•chronic (daily) treatment for asthma
10.History or presence, i.e any use of illicit or prescription drugs or alcohol constituting an abuse pattern
11.Use of other investigational drugs during the study participation
12.Patients using (or having used within 4 weeks or 5 half-lives, whichever is greater before initial dosing) concomitant medications that are potent inducers of CYP2C9 (see Appendix 3 )
13.Pregnant or nursing (lactating) women
14.Have received any vaccination with live or live attenuated vaccines (including for varicella-zoster virus or measles) within 2 months prior to dosing in the extension
15.Have received total lymphoid irradiation or bone marry transplantation
16.Any of the following abnormal laboratory values at entering the extension assessment:
• Total bilirubin greater than the ULN unless in context of Gilbert’s syndrome
• Conjugated bilirubin greater than the ULN
• AP greater than 1.5 x ULN
• AST or SGOT, ALT or SGPT greater than 2 x ULN
• GGT grea

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

Health Condition(s) or Problem(s) studied

Relapsing multiple sclerosis
MedDRA version: 17.0 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: BAF312
Product Code: BAF312
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: siponimod
CAS Number: 1234627-85-0
Current Sponsor code: BAF312
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
Product Code: BAF312
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Siponimod
CAS Number: 1234627-85-0
Current Sponsor code: BAF312
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 Name: BAF312
Product Code: BAF312
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: siponimod
CAS Number: 1234627-85-0
Current Sponsor code: BAF312
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 Name: BAF312
Product Code: BAF312
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: siponimod
CAS Number: 1234627-85-0
Current Sponsor code: BAF312
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)

Timepoint(s) of evaluation of this end point: Periodically throughout the study and at Month 60/End of study

Secondary Objective: To evaluate long-term efficacy on clinical grounds
• relapse rate
• disability progression
To evaluate long-term efficacy on paraclinical grounds
• neuroradiological measures of neurodegeneration

Main Objective: To evaluate long-term safety and tolerability.
Specific emphasis will be on
•effects on cardiac conduction during the titration of the study drug
• long term blood pressure effects
• viral infections
• macular edema
• dermatologic alterations

Primary end point(s): Evaluate long term safety and tolerability

Secondary Outcome(s)

Secondary end point(s): To evaluate long-term efficacy on clinical gorunds
To evaluate long-term efficacy on paraclinical grounds

Timepoint(s) of evaluation of this end point: Periodically throughout the study and at Month 60/End of Study

Secondary ID(s)

2009-014392-51-ES

CBAF312A2201E1

NCT01185821

Source(s) of Monetary Support

Novartis Pharma Services AG