Evaluation of Patient Retention of Fingolimod vs. Currently Approved Disease Modifying Therapy in Patients With Relapsing Remitting Multiple Sclerosis.

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01623596
• Date of registration: 18/06/2012
• Prospective Registration: No
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Evaluation of Patient Retention of Fingolimod vs. Currently Approved Disease Modifying Therapy in Patients With Relapsing Remitting Multiple Sclerosis. PREFERMS
• Scientific title: A 12-month, Prospective, Randomized, Active-controlled, Open-label Study to Evaluate the Patient Retention of Fingolimod vs. Approved First-line Disease Modifying Therapies in Adults With Relapsing Remitting Multiple Sclerosis (PREFERMS)
• Date of first enrolment: June 8, 2012
• Target sample size: 881
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01623596
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

Puerto Rico, United States

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

Inclusion Criteria:

1. written informed consent must be obtained prior to any assessment being performed.

2. Male and female patients aged 18-65 years inclusive.

3. Patients diagnosed with relapsing remitting MS, defined by the 2010 revised McDonald
criteria (Pollman et al, 2011) (Appendix 1).

4. EDSS score of less than or equal to 6.

5. Patients naive to treatment or who have been treated with no more than one class of
DMT previously (interferon ß preparation or glatiramer acetate), and who, per
investigator judgment, may benefit from a change of treatment class.

6. Patients who have been treated with DMF for less than 2 months total exposure and who
have a normal lymphocyte count at screening.

7. Women of childbearing potential must have a negative urine and serum ß-human chorionic
gonadotropin (ß-hCG) pregnancy test at screening and at baseline.

8. Before entry women must be:

- Post menopausal for at least 1 year, or

- Surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal
ligation or otherwise incapable of pregnancy, or

- Practicing a highly effective method of birth control if sexually active,
including hormonal prescription oral contraceptives, contraceptive injections,
contraceptive patch, intrauterine device, double barrier method (e.g., condoms,
diaphragm or cervical cap with spermicidal foam, cream or gel), or male partner
sterilization consistent with local regulations regarding use of birth control
methods for patients participating in clinical trials, for the duration of their
participation in the study, or

- Not heterosexually active (patients who are not heterosexually active at
screening must agree to utilize a highly effective method of birth control if
they become heterosexually active during their participation in the study) 4.2
Exclusion criteria

1. Use of other investigational drugs within 30 days of screening.

2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical
classes.

3. Prior exposure to fingolimod or any other S1P receptor modulating compounds.

4. History or presence of malignancy of any organ system (other than successfully treated
basal or squamous cell carcinoma of the skin or stage 0 carcinoma of the cervix),
treated or untreated, within the past 5 years, regardless of whether there is evidence
of local recurrence or metastases.

5. Patients diagnosed with Secondary Progressive Multiple Sclerosis (SPMS) or Primary
Progressive MS (PPMS).

6. Patients with a history of chronic disease of the immune system other than MS or a
known immunodeficiency syndrome.

7. Patients who have been treated with:

• Natalizumab, mitoxantrone, cladribine, rituximab, alemtuzumab, ofatumumab,
ocrelizumab at any time before randomization

• Immunoglobulins, or pulse of corticosteroids with more than 6 months cumulative
exposure

• Immunosuppressive/chemotherapeutic medications (e.g., methotrexate, azathioprine,
cyclophosphamide, cellcept, Cytoxan, IVIG) with more than 6 months of cumulative
exposure and within 6 months prior to randomization

• Corticosteroids or adrenocorticotropic hormones in the past 30 days before
randomization. Patients that require corticosteroids for a relapse during the
screening period may be rescreened 30 days after the last dose.

8. History of treatment with both classes of approved first line DMT (interferon ß
preparation and glatiramer acetate) or DMF exposure of 2 months or longer.

9. Patients with uncontrolled diabetes mellitus (HbA1c > 7%).

10. Diagnosis of macular edema during the screening phase. Patients with a history of
macular edema will be allowed to enter the study provided that they do not have
macular edema at the screening visit.

11. Patients with active systemic bacterial, viral or fungal infections, or known to have
AIDS, Hepatitis B, Hepatitis C infection or positive HIV antibody, Hepatitis B surface
antigen or Hepatitis C antibody tests.

12. Patients without history of chickenpox or without vaccination against varicella-zoster
virus at screening (patients may be vaccinated and rescreened one month or longer
after vaccination).

13. Patients who have received any live or live attenuated vaccines (including for
varicella-zoster or measles) within 1 month prior to baseline.

14. Patients with any medically unstable condition as assessed by the investigator.

15. Patients with a history of the following cardiovascular conditions:

• Cardiac arrest.

• myocardial infarction, unstable angina, stroke, transient ischemic attack,
decompensated heart failure requiring hospitalization, or Class III/IV heart failure
(Appendix 3).

• Congestive heart failure.

• Hypertension that is not controlled with prescribed medications. These patients may
be rescreened if blood pressure is stabilized with treatment.

• Cerebrovascular disease.

• History or presence of Mobitz Type II 2nd degree or 3rd degree AV block or sick
sinus syndrome, unless patient has a pacemaker.

• Patients at higher risk of symptomatic bradycardia or heart block because of a
coexisting medical condition or certain concomitant medications.

• Patients randomized to the fingolimod arm with prolonged QTc interval at screening
(corrected QT interval > 450 ms in males and > 470 ms in females); for patients
randomized to the fingolimod treatment arm before dosing (baseline) or during the
6-hour observation period; and those patients at additional risk for QT prolongation
(e.g., hypokalemia, hypomagnesemia, congenital long-QT syndrome), or on a concomitant
therapy with QT prolonging drugs with a known risk of Torsades de pointes (e.g.,
citalopram, chlorpromazine, haloperidol, methadone, erythromycin).

- Patients receiving class Ia or Class III antiarrhythmic drugs (Appendix 6)

- Patients receiving concurrent therapy with drugs that slow the heart rate or
atrioventricular conduction (e.g., beta blockers, digoxin, or heart-rate slowing
calcium channel blockers such as diltiazem, verapamil or digoxin). The
possibility to switch to drugs that do not slow the heart rate or
atrioventricular conduction should be evaluated by the physician prescribing
these drugs before initiating fingolimod treatment.

- History of sick sinus


Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Relapsing Remitting Multiple Sclerosis

Intervention(s)

Drug: Disease Modifying therapy

Drug: Fingolimod

Primary Outcome(s)

Participant Retention Rate Over 12 Months [Time Frame: at 12 months]

Secondary Outcome(s)

Change From Baseline of Symbol Digit Modalities Test (SDMT) Scores (Oral Test) by Visit (Randomized Treatment / Randomized Phase) [Time Frame: baseline, 6 months, 12 months, and Last assessment which is either at Month 12 or at early discontinuation]

Change From Baseline of Symbol Digit Modalities Test (SDMT) Scores (Written Test) by Visit (Randomized Treatment / Randomized Phase) [Time Frame: baseline, 6 months, 12 months, Last assessment which is either at Month 12 or at early discontinuation]

Primary and Secondary Reasons for Discontinuation From Randomized Treatment: Randomized Set [Time Frame: at 12 months]

Number of Satisfied Participants Per Medication Satisfaction Questionnaire (MSQ) Score [Time Frame: Baseline, 1 month, 3 months, 6 months, 9 months, at 12 months & Last assessment during randomized phase which is either at Month 12 or at early discontinuation]

Percent Change From Baseline in Brain Volume From Month 12 to Last Visit (Randomized) [Time Frame: 12 months, and Last assessment which is either at Month 12 or at early discontinuation]

Secondary ID(s)

CFTY720DUS09

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 12/01/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01623596