Impact of Natalizumab versus Fingolimod on Central Nervous System (CNS) Tissue Damage and Recovery in Active Relapsing-Remitting Multiple Sclerosis (RRMS) Subjects

• Register: EUCTR
• Last refreshed on: 16 January 2017
• Main ID: EUCTR2013-004622-29-DE
• Date of registration: 11/11/2014
• Prospective Registration: Yes
• Primary sponsor: Biogen Idec Research Limited
• Public title: Impact of Natalizumab versus Fingolimod on Central Nervous System (CNS) Tissue Damage and Recovery in Active Relapsing-Remitting Multiple Sclerosis (RRMS) Subjects
• Scientific title: A Multicenter, Randomized, Open-Label Study to Assess the Impact of Natalizumab versus Fingolimod on Central Nervous System Tissue Damage and Recovery in Active Relapsing-Remitting Multiple Sclerosis Subjects
• Date of first enrolment: 23/02/2015
• Target sample size: 540
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004622-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Australia, Czech Republic, Denmark, France, Germany, Italy, Spain, Sweden, United Kingdom, United States

Contacts

• Name: N/A
• Affiliation: Biogen Idec Research Limited

• Name: N/A
• Affiliation: Biogen Idec Research Limited

Key inclusion & exclusion criteria

Inclusion criteria:
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 treatment with BRACE-TA he/ she must have:
• 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: * with =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.
- If the subject is DMT naïve at study screening, he/she must have experienced =2 disabling relapses in the 12 months prior to study screening. In addition, they must have had =1 new T1-Gd+ lesion 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 prior to study screening.
- For subjects with highly active disease (defined by the criteria below), regardless of whether they are disease-modifying therapy (DMT)-naive or had previous exposure to BRACE TA, he/sge 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:
Excl Crit for MS Patients:
- Hist. of or pos. test result at study screening for HIV
- Hist. or pos. test result at study screening for HCV antibody or current hep B infect. (def. as positive for HBsAg and/or HBcAb). Subj 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
- Hist. 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 clin. sig. infectious illness (e.g., pneumonia, septicemia) within the 1 month prior to study screening
- History of drug or alcohol abuse within 1 year prior to study screening
- Exposure to IVIg, monoclonal antibodies, cytokines, growth factors, soluble receptors, other recombinant products, or fusion proteins within 1 year prior to study screening
- Prior history of immunosuppressant use (e.g., mitoxantrone,
azathioprine, methotrexate, cyclophosphamide, mycophenolate,
cladribine, rituximab) in the last 12 months prior to study screening.Treatment with IV and/or oral corticosteroids (topical corticosteroids are acceptable) within 4 weeks 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 particip. in investigational drug studies within 90 days prior to study screening or 5 times the compound's half-life, whichever is longer
- 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.
- Hist. or evidence of macular edema on ophthalmologic exam
- Hist. of congenital QT prolongation, unexplained hypokalemia,
myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure in last 6 months
- 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
- Treat. 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 (e.g., betablockers,heart-rate lowering calcium channel blockers such as
diltiazem, verapamil or digoxin), prolong the QTc interval, or are potent inducers of CYP450
- Hypertens. not controlled with prescribed

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

Health Condition(s) or Problem(s) studied

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

Multiple Sclerosis (MS)
MedDRA version: 18.0 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: Tysabri®
Product Name: AN100226, BG00002
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: NATALIZUMAB
CAS Number: 189261-10-7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 300-

Trade Name: Gilenya
Product Name: Fingolimod
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: fingolimod
CAS Number: 162359-56-0
Other descriptive name: FINGOLIMOD HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Weeks 4, 8, 12, 16, 20, 24

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.

Main Objective: The primary objective of the study is to assess the effect of natalizumab compared to fingolimod on the evolution of
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:
• MRI measures of CNS tissue destruction as measured by the number of new T1-Gd+ lesions.
• Various other MRI measures of disease activity.
• No Evidence of Disease Activity (NEDA)
• Relapse on treatment over 52 weeks.
• The change in information processing speed as measured by the Symbol Digit Modalities Test (SDMT).

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Weeks 4, 8, 12, 16, 20, 24, 52

Secondary end point(s): The secondary endpoints of this study are the follwoing:
• MRI endpoints:
o Cumulative number of new T1-Gd+ lesions .
o Change in total T1-hypointense and total T2-hyperintense lesion volumes.
o Cumulative number of new or enlarging T2 lesions.
• Proportion of subjects with NEDA according to the following definition:
o No relapses.
o No 12-week confirmed disability progression based on EDSS.*
o No new T1-Gd+ lesions on brain MRI.
o No new or enlarging T2-hyperintense lesions.
• Time to first relapse, cumulative risk of relapses and time to complete recovery from first relapse. **
• Change in information processing speed as measured by the SDMT from baseline to Week 24 and Week 52.

* Increase of 1.0 or more on the EDSS from a baseline score of 1.0 or more, or an increase of 1.5 or more from a baseline score of 0 that was sustained for 12 weeks (progression could not be confirmed during a relapse).
** 12-week confirmed complete Expanded Disability Status Scale (EDSS) recovery from first on-treatment relapse is defined as an EDSS score that is equal to or lower than the last pre-relapse EDSS score and sustained for at least 12 week

Secondary ID(s)

101MS408

2013-004622-29-IT

Source(s) of Monetary Support

Biogen Idec Research Limited