Comparison of Rebif Compared to Tecifdera on Six-month Outcomes in Patients With Relapsing-remitting MS

To compare two commonly used MS medications, IFN β-1a subcutaneous three times per week (Rebif) and oral twice daily dimethyl fumarate (Tecfidera), on mean number of new or enlarging T2 lesions at 6 months in adults with relapsing-remitting multiple sclerosis who are prescribed these medications and receive a 6 month MRI scan as standard of care.

Primary objective To compare two commonly used MS medications, IFN β-1a subcutaneous three times per week (Rebif) and oral twice daily dimethyl fumarate (Tecfidera), on mean number of new or enlarging T2 lesions at 6 months in adults with relapsing-remitting multiple sclerosis who are prescribed these medications and receive a 6 month MRI scan as standard of care.

Key secondary objective To compare Rebif vs. Tecfidera in reducing the T2 lesion volume, number of T1 black holes, gadolinium-enhancing lesions, brain parenchymal fraction, brain white matter fraction and brain gray matter fraction on the 6 month MRI.

Other secondary objectives

• To compare the two treatments on the following clinical efficacy measures which are routinely obtained as part of our clinical practice: Expanded disability status score (EDSS), ambulation index (AI), disease steps and number of relapses. In addition we will obtain the MSFC-4, which in addition to the AI which is routinely done, will include the symbol digit modalities test (SDMT), low contrast visual acuity, and 9 hole peg test.
• To compare adherence to the two treatments using an adherence question.

Tertiary objectives

• To compare the two treatments on optical coherence tomography (OCT) and visual acuity measures.
• To compare the following patient reported outcomes: MSQOL-54 (MSQOL54), Modified MOS Social Support Survey (MSSS), Modified Fatigue Impact Scale (MFIS), Center for Epidemiological Studies Depression Scale (CES-D).
• To compare cognitive function using the brief repeatable battery of neuropsychological tests in Multiple Sclerosis (BRB) which includes the following cognitive measures: Symbol Digit Modalities Test (SDMT), Selective Reminding Test (SRT), 10/36 Spatial Recall Test (10/36), Controlled Oral Word Association Test (COWAT).
• To compare the following Pharmacoeconomic outcomes: Healthcare Utilization and Costs, QUALY, Unscheduled visits (office, ER, hospital), out-of-pocket expenses (e.g., durable medical equipment, copays), Work Productivity and Activity Impairment (WPAI), Treatment satisfaction questionnaire (Treatment Satisfaction for Medication Questionnaire (TSQM))

Design: The study is a single center, 6-month, randomized, parallel-group, single blind study to compare two FDA approved treatments for MS (Rebif and Tecfidera) in adults with relapsing-remitting MS. 120 subjects will be treated with each medication (total 240 patients). Randomization will ensure balanced patient groups and prevent bias. Patients will be prescribed the medication by their treating physician who will follow the patient in a open fashion as part of standard of care for MS including obtaining MRI imaging at 6 months. At 6 months, patients will have a neurologic exam by an independent examining physician and administration of questionaires by study staff blinded to their treatment.

Methods: Relapsing-remitting patients beginning medication and deemed suitable for treatment with Rebif or Tecfidera as part of standard of care for MS will be explained the nature of the study, after which informed consent will be obtained. They will undergo a baseline visit and then randomized to one of the two treatments. Blood samples for biomarker studies will be collected at the baseline visit and at 6 months. MRI is obtained prior to therapy and at 6 months as part of standard of care. Following the completion of the 6 month study period, subjects are able to continue on either of the two treatments or switch to another agent according to their own preference and following discussions with their treating MS neurologist.

Subjects who discontinue treatments prior to the 6 month period are free to begin another therapy. Upon discontinuation of treatment, subjects will complete the end of study (EOS) visit as soon as possible and will be followed for the duration of the 6-month treatment phase.

Inclusion Criteria:

1. Male and female subjects aged 18-65 years old, inclusive.
2. A diagnosis of MS as defined by the McDonald 2010 criteria for MS.
3. Relapsing form of MS, defined as at least one relapse in the prior 5 years.
4. Expanded Disability Status Scale (EDSS) score of 0 to 5.5, inclusive.
5. English language skills adequate for the completion of questionnaires and cognitive measures.

Exclusion Criteria:

1. Subjects with progressive MS.

2. Subjects with a contraindications for standard treatment with Rebif or Tecfidera including GI disease, needle phobia, liver disease.

3. Subjects treated with:

   • High dose intravenous immunoglobulin within 2 months prior to study entry
   • Natalizumab within 3 months prior to study entry
   • Immunosuppressive/immunomodulatory medications including cyclophosphamide, mitoxantrone, azathioprine, methotrexate, rituximab, ofatumumab, ocrelizumab, or alemtuzumab at any time.

4. Subjects with absolute lymphocyte count < 800 cells (mm3).

5. Subjects with any of the following neurologic/psychiatric disorder:

   • Severe depression during the past 12 months before screening;
   • History of substance abuse (treatment or alcohol) or any other factor (i.e., serious psychiatric condition) that may interfere with the subject's ability to cooperate and comply with the study procedures;

6. Subjects unable to undergo MRI scans, including claustrophobia or history of hypersensitivity to gadolinium-DTPA.

7. Pregnant or nursing females, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive HCG laboratory test.

8. Female subjects of childbearing potential, defined as all females physiologically capable of becoming pregnant, unless they agree to abstinence or, if sexually active, the use of contraception.

9. History of hypersensitivity to any of the study treatments or to treatments of similar chemical classes.

10. Subjects with abnormal Liver Function Test (LFT) levels