Impact of Natalizumab versus Fingolimod on Central Nervous System (CNS) Tissue Damage and Recovery in Active Relapsing-Remitting Multiple Sclerosis (RRMS) Subjects
- Conditions
- Multiple Sclerosis (MS)MedDRA version: 19.0Level: PTClassification code 10063399Term: Relapsing-remitting multiple sclerosisSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2013-004622-29-DK
- Lead Sponsor
- Biogen Idec Research Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 540
Inclusion Criteria for MS Patients:
- Must have a documented diagnosis of relapsing MS (McDonald 2010 Criteria [Polman 2011]) at study screening.
- for subjects with a previous history of treatment with BRACE-TA he/she must have:
• Been on therapy for at least 6 months (unless experiencing highly active disease; see #6 below)
• At least 9 T2-hyperintense lesions on a brain MRI scan, and
• Experienced =1 relapse while on therapy within the last 6 months prior to study screening and either:
* =1 new T1-Gd+ lesion or =2 new T2 lesions on a brain MRI scan performed =6 months prior to study screening
or
* =2 new T2 lesions on a brain MRI scan performed =6 months prior to study screening, with comparison made to a T2
MRI scan performed up to 18 months before study screening.
- For subjects with highly active disease (defined by the criteria below), regardless of whether they are disease-modifying therapy (DMT)-naïve or had previous exposure to BRACE TA, he/she must have had:
• =2 disabling relapses in the 12 months prior to study screening and either:
?* =1 new T1 Gd+ lesion on a brain MRI scan performed =6 months prior to study screening
or
?* =2 new T2 lesions on a brain MRI scan performed =6 months prior to study screening with comparison made to a T2
MRI scan performed up to 18 months before study screening
- Willing to take natalizumab or fingolimod as the only DMTs for the duration of the study treatment period.
- Must have an EDSS score from 0 to 5.5 inclusive at study screening.
Inclusion Criteria for Healthy Volunteers:
- Subjects who are generally healthy as demonstrated by physical examination and by medical history, with no history or evidence of major illnesses, diseases, or disorders.
- Subjects of childbearing potential must practice effective contraception and be willing and able to continue contraception for duration of the study.
- No history of drug or alcohol abuse (as defined by the Investigator) within 1 year prior to study screening.
- Willing and able to comply with scheduled visits and imaging services.
NOTE: Other protocol defined Inclusion criteria may apply
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 540
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Exclusion Criteria for MS Patients:
- History of or positive test result at study screening for HIV
- History or positive test result at study screening for HCV antibody or current hepatitis B infection (defined as positive for HBsAg and/or HBcAb). Subjects with immunity to hepatitis B from either active vaccination (defined as negative HBsAg, positive HBsAb and negative HBcAb) or from previous natural infection (defined as negative HBsAg, positive HBsAb immunoglobulin G, and positive HBcAb) are eligible to participate in the study
- Prior treatment with natalizumab or fingolimod
- Diagnosis of PPMS and/or SPMS
- History of or known active malignant disease, including solid tumors and hematologic malignancies (subjects with cutaneous basal and squamous cell carcinoma that has been completely excised and considered cured prior to study screening remain eligible)
- History of opportunistic infections (including PML) or any clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic,metabolic, urologic, pulmonary, neurologic (other than MS), dermatologic, psychiatric, and renal condition, or other major disease
- A clinically significant infectious illness (eg, pneumonia, septicemia) within the 1 mth prior to study screening
- History of drug or alcohol abuse within 1 yr prior to study screening
- Exposure to IVIg, monoclonal antibodies, cytokines, growth factors, soluble receptors, other recombinant products, or fusion proteins within 1 yr prior to study screening
- History of immunosuppressant use (eg, mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate, cladribine, rituximab) in the last 12 mths prior to study screening. Treatment with IV and/or oral corticosteroids (topical corticosteroids are acceptable) within 4 wks of baseline DTI-MRI assessment
- An MS relapse that has occurred within the 30 days prior to randomization and/or the subject has not stabilized from a previous relapse prior to randomization
- Current/previous participation in investigational drug studies
- Subject has any contraindications to fingolimod or natalizumab, as described in the respective Prescribing Information or has any medical condition as described in the warnings and precautions of the respective Prescribing Information that makes the subject unsuitable for participation in the study
- Subject treated with teriflunomide who did not undergo an accelerated elimination procedure prior to study screening.
- History or evidence of macular edema on ophthalmologic exam
- History of congenital QT prolongation, unexplained hypokalemia, myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure in last 6 mths
- Mobitz type II second degree or third degree AV block or sick sinus syndrome, symptomatic bradycardia, recurrent syncope, or severe untreated sleep apnea
- Baseline corrected QTc (Fridericia [QTcF] or Bazett's [QTcB] formula) interval =470 ms in females and =450 ms in males
- Treatment with Class Ia (e.g., procainamide, quinidine, ajmaline, disopyramide) or Class III (amiodarone, bretylium, dofelitide, sotalol, ibulitide, azilimide) anti-arrhythmic drugs
- Concurrent therapy with drugs that slow heart rate (eg, beta-blockers, heart-rate lowering calcium channel blockers such as diltiazem, verapamil or digoxin), prolong the QTc interval, or are potent inducers of CYP450
- Hypertension not controlled with prescribed medications
- History of severe
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the study is to assess the effect of natalizumab compared to fingolimod on the evolution of<br>new on-treatment T1-gadolinium-enhancing (Gd+) lesions to persistent black holes (PBH) over 52 weeks.;Secondary Objective: The secondary objectives of this study are to assess the effect of natalizumab compared to fingolimod on:<br>• MRI measures of CNS tissue destruction as measured by the number of new T1-Gd+ lesions.<br>• Various other MRI measures of disease activity.<br>• No Evidence of Disease Activity (NEDA)<br>• Relapse on treatment over 52 weeks.<br>• The change in information processing speed as measured by the Symbol Digit Modalities Test (SDMT).;Primary end point(s): The primary endpoint of the study is the cumulative number of =6-month confirmed T1-hypointense lesions (i.e., PBH) arising from new on-treatment T1-Gd+ lesions.;Timepoint(s) of evaluation of this end point: Weeks 4, 8, 12, 16, 20, 24
- Secondary Outcome Measures
Name Time Method