Oral Cladribine in Early Multiple Sclerosis (MS)

This will be a randomized, double blind, three-arm, placebo-controlled, multi-center trial to
evaluate the safety and efficacy of oral cladribine versus placebo in the treatment of
subjects who have sustained a first clinical demyelinating event within 75 days prior to the
Screening. Subjects must have a minimum of 2 clinically silent lesions on the Screening
magnetic resonance imaging (MRI).

The study will include a pre-study evaluation period (Screening period: between 10 and 28
days prior to the start of treatment with blinded study medication (oral cladribine or
placebo).

Depending upon the clinical course of their MS, subjects will then proceed from the ITP to
either the Maintenance Treatment Period (with open-label interferon-beta treatment) or LTFU
period (with either open-label low-dose cladribine or no additional treatment (if no
progression to MS has been noted after the initial treatment period). The single primary
endpoint for the overall study, which will be determined during the ITP, is time to
conversion to MS (from randomization), according to the Poser criteria.

For every subject, eligibility for study enrollment and entry into each of the study periods,
and diagnosis of conversion to either McDonald MS or CDMS must be confirmed and approved by a
Sponsor appointed study Adjudication Committee.

Inclusion Criteria:

- Male or female between 18 and 55 years old, inclusive

- Weighed between 40 to 120 kilogram (kg), inclusive

- Subject has experienced a single, first clinical event suggestive of MS within 75 days
prior to the Screening visit, (clock starts 24 hours after onset). The event must be a
new neurological abnormality present for at least 24 hours, either mono- or
polysymptomatic

- Subject has at least two clinically silent lesions on the T2-weighted MRI scan, at
screening, with a size of at least 3 millimeter (mm), at least one of which is ovoid
or periventricular or infratentorial on screening MRI

- Subject has EDSS 0 - 5.0 at Screening

- Subject has no medical history or evidence of latent tuberculosis infection (LTBI) or
active tubercular disease, as evidenced by the Mantoux tuberculosis (TB) skin test or
a comparable sensitive test according to local regulations/guidelines (if the Mantoux
test is not available), and/or a chest X-ray

- Subject has normal hematological parameters at Screening, as defined by the central
laboratory that performed all the assessments

- If female, she must:

- be neither pregnant nor breast-feeding, nor attempting to conceive and

- use a highly effective method of contraception throughout the entire duration of
the study and for 90 days following completion of the last dose of study
medication. A highly effective method of contraception is defined as those which
result in a low failure rate (that is less than 1 percent per year) when used
consistently and correctly such as implants, injectables, combined oral
contraceptives, some intrauterine devices, sexual abstinence or vasectomized
partner, or

- be post-menopausal or surgically sterilized (Note: for Danish sites only,
subjects should use a hormonal contraceptive or intrauterine device for the
duration of the trial)

- Male subjects must be willing to use contraception to avoid impregnating partners
throughout the study, and for 90 days following the last dose of study medication

- Be willing and able to comply with study procedures for the duration of the study

- Subject has to provide written informed consent voluntarily, including, for United
states of America (USA), subject authorization under Health Insurance Portability and
Accountability Act (HIPAA), prior to any study-related procedure that is not part of
normal medical care

- Subject has refused any treatment already available for clinically isolated syndrome
(CIS) such as interferons or glatiramer acetate, at the time of entry into the Initial
Treatment Period of this study

Exclusion Criteria:

- Subject has a diagnosis of MS (per McDonald criteria, 2005)

- Subject has any other disease that could better explain the subject's signs and
symptoms

- Subject has complete transverse myelitis or bilateral optic neuritis

- Subject using or has used any other approved MS disease modifying drug (DMD)

- Subject has used any investigational drug or undergone an experimental procedure
within 12 weeks prior to Study day 1

- Subject received oral or systemic corticosteroids or adrenocorticotropic hormone
(ACTH) within 30 days prior to screening MRI. The MRI had to be performed 30 days
after the oral or systemic corticosteroids or ACTH treatment. In case this interfered
with MRI timing the screening period could be extended accordingly.

- Subject has abnormal total bilirubin, or aspartate aminotransferase (AST) or alanine
aminotransferase (ALT) or alkaline phosphatase greater than 2.5 times the upper limit
of normal

- Subject suffered from current autoimmune disease other than MS

- Subject suffered from psychiatric illness (including history of, or concurrent, severe
depressive disorders and/or suicidal ideation) that in the opinion of the investigator
creates undue risk to the subject or could affect compliance with the study protocol

- Subject suffered from major medical illness such as cardiac (for example angina,
congestive heart failure or arrhythmia), endocrinologic, hepatic, immunologic,
metabolic, renal, pulmonary, gastrointestinal, dermatologic, or other major disease
that would preclude the administration of oral cladribine

- Subject has a history of seizures not adequately controlled by medications

- Subject has a known allergy to cladribine, interferon-beta, the excipient(s) of the
study medications, or to gadolinium- diethylenetriamine penta-acetic acid (DTPA)

- Subject has any renal condition that would preclude the administration of gadolinium
(for example acute or chronic severe renal insufficiency (glomerular filtration rate
[GFR] less than 30 milliliter per minute per 1.73 square meter [mL/min/1.73 m^2])

- Subject has a history of chronic or clinically significant hematological abnormalities

- Subject has a history of active or chronic infectious disease or any disease that
compromises immune function (for example human immunodeficiency virus positive [HIV+],
human T-lymphotrophic virus [HTLV-1], Lyme disease, latent tuberculosis infection
[LTBI] or TB, insulin-dependent diabetes).

- Subject has previously been screened in this study (signed an informed consent) and
then withdrawn

- Subject has received any immunomodulatory or immunosuppressive therapy) at any time
prior to Study Day 1, including, but not limited to, the following products: any
interferon, glatiramer acetate (Copolymer I), cyclophosphamide, cyclosporine,
methotrexate, linomide, azathioprine, mitoxantrone, teriflunomide, laquinimod,
cladribine, total lymphoid irradiation, anti-lymphocyte monoclonal antibody treatment
(for example natalizumab, alemtuzumab/Campath, anti-cluster of differentiation 4
[CD4]), intravenous immunoglobulin G (IVIG), cytokines or anti-cytokine therapy

- Subject has received experimental MS treatment

- Subject has a history of alcohol or drug abuse

- Subject has intolerance or any contraindication to both paracetamol (acetaminophen)
and ibuprofen

- Subject has inability to administer subcutaneous injections either by self or by
caregiver

- Subject has prior or current malignancy (with the exception of in situ basal or
squamous cell skin cancer surgically removed without recurrence for at least five
years)

- Subject has a positive stool hemoccult test at Screening