Please select the eligibility criteria that correspond to the clinical trial below.
Title: Long-term Extension of the Multinational, Double-blind, Placebo Controlled Studies PDY6045 and PDY6046 to Document the Safety of Teriflunomide When Added to Treatment With Interferon-Beta or Glatiramer Acetate in Patients With Multiple Sclerosis With Relapses
Brief Summary: The primary objective was to evaluate the long-term safety and tolerability of teriflunomide when added to treatment with interferon-β \[IFN-β\] or glatiramer Acetate \[GA\] in patients with multiple sclerosis \[MS\] with relapses.

Secondary objectives were to evaluate the long-term effect on relapse rate, disability progression and Magnetic Resonance Imaging \[MRI\] parameters.

This study is the extension study of the PDY6045 (NCT00489489) and PDY6046 (NCT00475865) studies. Participants who successfully completed the initial study were offered to continue their treatment (same compound, same dose) for 24 additional weeks.


Options:
A: Inclusion Criteria:

* PDY6045 or PDY6046 participant who:

  * completed the week 24 visit of either study PDY6045 or PDY6046,
  * was still meeting eligibility criteria for receiving treatment,
  * had agreed to continue stable dose of Interferon-β \[IFN-β\] or Glatiramer Acetate \[GA\] and consented to continue on treatment.

Exclusion Criteria:

* Any known condition or circumstance that would have prevented in the investigator's opinion, compliance or completion of the study

The above information is not intended to contain all considerations relevant to patient's potential participation in a clinical trial.
B: Inclusion Criteria:

* Male or female between 18 and 55 years old, inclusive
* Weighed between 40 to 120 kilogram (kg), inclusive
* Participant 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
* Participant 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
* Participant has EDSS 0 - 5.0 at Screening
* Participant 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
* Participant 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, participants should use a hormonal contraceptive or intrauterine device for the duration of the trial)
* Male participants 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
* Participant has to provide written informed consent voluntarily, including, for United states of America (USA), participant authorization under Health Insurance Portability and Accountability Act (HIPAA), prior to any study-related procedure that is not part of normal medical care
* Participant 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:

* Participant has a diagnosis of MS (per McDonald criteria, 2005)
* Participant has any other disease that could better explain the participant's signs and symptoms
* Participant has complete transverse myelitis or bilateral optic neuritis
* Participant using or has used any other approved MS disease modifying drug (DMD)
* Participant has used any investigational drug or undergone an experimental procedure within 12 weeks prior to Study day 1
* Participant 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.
* Participant 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
* Participant suffered from current autoimmune disease other than MS
* Participant 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 participant or could affect compliance with the study protocol
* Participant 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
* Participant has a history of seizures not adequately controlled by medications
* Participant has a known allergy to cladribine, interferon-beta, the excipient(s) of the study medications, or to gadolinium- diethylenetriamine penta-acetic acid (DTPA)
* Participant 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 \[mL/min/1.73 m\^2\])
* Participant has a history of chronic or clinically significant hematological abnormalities
* Participant 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).
* Participant has previously been screened in this study (signed an informed consent) and then withdrawn
* Participant 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
* Participant has received experimental MS treatment
* Participant has a history of alcohol or drug abuse
* Participant has intolerance or any contraindication to both paracetamol (acetaminophen) and ibuprofen
* Participant has inability to administer subcutaneous injections either by self or by caregiver
* Participant 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)
* Participant has a positive stool hemoccult test at Screening
C: Key Inclusion Criteria:

* Must have a confirmed diagnosis of relapsing multiple sclerosis (RMS), as defined by McDonald criteria 1 through 4 (Polman, 2005)
* Must have an EDSS score between 0.0 and 5.0.
* Must have experienced at least 2 relapses that have been medically documented within the last 3 years with at least one occurring in the last 12 months

Key Exclusion Criteria:

* Other chronic disease of immune system, malignancies, urologic, pulmonary, gastrointestinal disease
* Pregnant or nursing women
* Prior treatment with interferon could not exceed 4 weeks and subjects must have discontinued interferon treatment 6 months prior to Baseline

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
D: Key Inclusion Criteria for MS Patients:

* Must have a documented diagnosis of relapsing MS (McDonald 2010 Criteria) at study screening with EDSS score from 0.0 to 5.5.
* If the subject is on Betaseron, Rebif, Avonex, Copaxone, Extavia, Tecfidera, and Aubagio (BRACE-TA) at study screening:
* He/she must have been on therapy for at least 6 months (unless experiencing highly active disease), have at least 9 T2-hyperintense lesions on a brain MRI scan, and have experienced ≥1 relapse within the last 6 months prior to study screening with ≥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
* If the subject has highly active disease, regardless of whether they are disease-modifying therapy (DMT)-naïve or had previous exposure to Betaseron, Rebif, Avonex, Copaxone, Extavia, Tecfidera, and Aubagio (BRACE-TA), they 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

Key Exclusion Criteria for MS Patients:

* Diagnosis of Primary Progressive Multiple Sclerosis and/or Secondary Progressive Multiple Sclerosis.
* History or positive test result at study screening for human immunodeficiency virus (HIV), hepatitis C virus (HCV) antibody or current hepatitis B infection (defined as positive for hepatitis B surface antigen \[HBsAg\] and/or hepatitis B core antibody \[HBcAb\]).
* Prior treatment with natalizumab or fingolimod.
* 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 or any clinically significant major disease, as determined by the Investigator.
* A clinically significant infectious illness (e.g., pneumonia, septicemia) within the 1 month prior to study screening.
* History of drug or alcohol abuse (as defined by the Investigator) within 1 year prior to study screening.
* Prior history of immunosuppressant use (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate, cladribine, rituximab), or exposure to intravenous immunoglobulin (IGIV), monoclonal antibodies, cytokines, growth factors, soluble receptors, other recombinant products, or fusion proteins in the last 12 months prior to study screening.
* History of myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure in last 6 months.
* 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 (e.g., beta-blockers, heart-rate lowering calcium channel blockers such as diltiazem or verapamil, or digoxin).
* Hypertension not controlled with prescribed medications.
* History of severe respiratory disease, pulmonary fibrosis or class III or IV chronic obstructive pulmonary disease.
* The use of live or live attenuated vaccination within 8 weeks of study screening.

Key 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.

Key Exclusion Criteria for Healthy Volunteers:

* Claustrophobia sufficient to interfere with generating reliable MRI scans.
* History of other major illness including neurological disorders as determined by the Investigator.
* Presence of a metal device affected by MRI (e.g., any type of electronic, mechanical or magnetic implant, cardiac pacemaker, aneurysm clips, implanted cardiac defibrillator) or potential ferromagnetic foreign body (metal slivers, metal shavings, other metal objects), which would be a contraindication for MRI.
* Women who are currently pregnant or breastfeeding, or who have a positive pregnancy test result at screening.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Answer: A