Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Open-label, Multicenter Phase II Extension of Study 28063 (ATAMS) to Obtain Long-term Follow-up Data in Subjects With Relapsing Multiple Sclerosis Treated With Atacicept for up to 5 Years (ATAMS-Extension)
Brief Summary: This study (28851) is a long-term follow-up study of subjects enrolled in ATAMS study 28063 (NCT00642902). The aim of this study is to monitor the safety and tolerability of atacicept administered for up to 5 years to subjects with relapsing multiple sclerosis (RMS).

This extension study consists of two parts. Part A will be double blind and Part B will be open label. During Part A, subjects initially randomized to atacicept will continue to receive the atacicept dose to which they have been randomized in study 28063 (ATAMS) once a week subcutaneously (under the skin). Subjects randomized to placebo in ATAMS will receive atacicept at 150 mg once a week subcutaneously during Part A. Once the results of ATAMS are available and the atacicept dose with the best benefit / risk ratio has been identified, all subjects will be switched to this dose and will continue the extension study open-label (Part B). Throughout the study, subjects and investigators will remain blinded with respect to initial and part A treatment allocation/dose.


Options:
A: Inclusion Criteria:

1. The subject must have undergone a single clinical attack.
2. The subject must have a unifocal clinical presentation.
3. The subject should be enrolled within the period of 90 days after onset of a single unifocal clinical attack (index attack).
4. There must be 2 or more cerebral lesions highly suspicious of multiple sclerosis (MS) on the screening Magnetic Resonance Imaging (MRI), measuring 6mm or more in diameter.
5. Subjects must be between the ages of 18 and 45 years inclusive.
6. Subjects must not have taken corticosteroids within the 30 days prior to the MRI at the baseline visit.
7. Subjects may be male or female. Women of child-bearing potential must practice a medically acceptable method of birth control. Acceptable methods include oral contraceptive, contraceptive patch, long-acting injectable contraceptive, or double-barrier method (condom or intrauterine device with spermicide).
8. The subjects must be willing and able to give written informed consent, prior to entering the study.

Exclusion Criteria:

1. Multifocal clinical presentation.
2. Diseases other than MS responsible for the clinical/MRI presentation. The following laboratory tests must be part of the subject's medical history for differential diagnosis of clinically isolated syndrome (CIS): erythrocyte sedimentation rate (ESR), antinuclear antibody (ANA), complement (C3, C4) and anticardiolipin IgG - IgM. In the event that the results of these tests are inconclusive, the following additional tests may be requested by the Eligibility Evaluation Committee: syphilis screening, vitamin B12 and folic acid. In the case of spinal cord CIS presentation, a spinal cord MRI is required for confirmation of diagnosis in the medical history of the subject.
3. Use of experimental or investigational drugs, including IV immunoglobulin, and/or participation in an investigational drug study within 6 months prior to study entry.
4. Use of interferon agents within 6 months prior to the screening visit.
5. Chronic corticosteroid treatment (more than 30 consecutive days) in the 6 months prior to study entry.
6. Pregnancy or breast feeding.
7. Subjects who experience a relapse between the screening (month -1) and baseline (month 0) visits.
8. Life-threatening or other clinically significant disease.
9. A medical or psychiatric condition that affects the subject's ability to give informed consent, or to complete the study, or if the subject is considered by the treating neurologist/physician to be, for any other reason, an unsuitable candidate for this study.
10. A known history of sensitivity to mannitol.
11. A known history of sensitivity to gadolinium.
12. Inability to successfully undergo MRI scanning.
B: Inclusion Criteria:

* Willing and able to sign written Informed Consent;
* Female and male subjects aged 18-55 years inclusive at the time of Informed Consent signing;
* Diagnosis of RRMS according to the revised McDonald criteria;
* Expanded Disability Status Scale (EDSS) score of 0.0 up to and including 5.5;
* Neurologically stable with no evidence of relapse within 30 days prior to randomization;
* Experienced at least 1 relapse in the year before first screening assessment;
* At least 1 T1-weighted Gadolinium enhancing (T1-GdE) lesion on routine brain MRI taken within 3 months of starting screening or on screening brain MRI (as confirmed by central imaging laboratory;
* Having a routine brain MRI showing maximally 15 T1-GdE lesions if scan is taken without subject receiving immuno-modulatory treatment, or a routine brain MRI showing maximally 5 T1-GdE lesions when taken while on immuno-modulatory treatment, or a screening MRI showing maximally 15 T1-GdE lesions;
* Must decline initiation or continuation of treatment with other available disease-modifying drugs for MS, for whatever reason, after having been informed about their respective benefits and possible adverse events by the investigator;
* Female subjects of childbearing potential must agree to practice appropriate contraceptive methods as assessed by the investigator.

Exclusion Criteria:

* Any life-threatening, medically unstable or otherwise clinically significant condition or findings other than MS, in particular neoplastic disease, seizure disorders, or psychiatric disease;
* Any clinically significant deviation from reference ranges in laboratory tests;
* Positive laboratory test results for human immunodeficiency virus (HIV), HBsAg or HCV at screening;
* Any significant deviation from reference ranges for hepatic function;
* Positive urine drug screen or history of substance abuse within the year before screening (any use of illicit or prescription drugs or alcohol constituting an abuse pattern in the opinion of the investigator);
* Having been treated with or having received

  1. at any time:

     * glatiramer acetate, cladribine, rituximab, cyclophosphamide, alemtuzumab, or other immunosuppressive treatments with effects potentially lasting for more than 6 months
     * total lymphoid irradiation or bone marrow transplantation
  2. within one year before screening:

     * mitoxantrone, but subject cannot be enrolled when mitoxantrone was taken at a cumulative lifetime dosing above 100 mg/m2
  3. within 6 months before screening:

     * fingolimod, immunoglobulins and/or monoclonal antibodies (including natalizumab), leflunomide, or putative MS treatments
     * chronic oral or injected corticosteroids or injected ACTH (more than 30 consecutive days)
  4. within 3 months before screening:

     * azathioprine, methotrexate
     * plasma exchange
     * any other experimental intervention, in particular experimental drugs
  5. within 1 month before screening:

     * Interferon-β 1a or 1b
     * short-term oral or injectable corticosteroids for treatment of a relapse
     * short-term ACTH
* Having, in the opinion of the investigator, consecutively failed on efficacy grounds two full and adequate courses of accepted treatment modalities (normally at least one year of treatment for each);
* Pregnancy or breastfeeding;
* Known hypersensitivity to gadolinium-containing products, glatiramer acetate or mannitol;
* Having an estimated glomerular filtration rate (eGFR) \< 50 mL/min/1.73m2;
* Inability to undergo (repeat) MRI investigations as judged by the investigator, e.g. due to claustrophobia, metal implants or fragments, tattoos or permanent make-up;
* Any reason why, in the investigator's opinion, the subject should not participate.
C: Inclusion Criteria:

1. Subjects must have a confirmed and documented MS diagnosis as defined by the Revised McDonald criteria \[Ann Neurol 2005: 58:840-846\], with a relapsing-remitting disease course.
2. Subjects must be ambulatory with converted Kurtzke EDSS score of 0-5.5.
3. Subjects must be in a stable neurological condition and free of corticosteroid treatment \[intravenous (iv), intramuscular (im) and/or per os (po)\] 30 days prior to screening (month -1).
4. Subjects must have had experienced one of the following:

   * At least one documented relapse in the 12 months prior to screening
   * At least two documented relapses in the 24 months prior to screening
   * One documented relapse between 12 and 24 months prior to screening with at least one documented T1-Gd enhancing lesion in an MRI performed within 12 months prior to screening.
5. Subjects must be between 18 and 55 years of age, inclusive.
6. Subjects must have disease duration of at least 6 months (from the first symptom) prior to screening.
7. Women of child-bearing potential must practice an acceptable method of birth control \[acceptable methods of birth control in this study include: surgical sterilization, intrauterine devices, oral contraceptive, contraceptive patch, long-acting injectable contraceptive, partner's vasectomy or double-barrier method (condom or diaphragm with spermicide).
8. Subjects must be able to sign and date a written informed consent prior to entering the study
9. Subjects must be willing and able to comply with the protocol requirements for the duration of the study.

Exclusion Criteria:

1. Subjects with progressive forms of MS
2. An onset of relapse, unstable neurological condition or any treatment with corticosteroids \[intravenous (iv), intramuscular (im) and/or per os (po)\] or ACTH between month -1 (screening) and 0 (baseline).
3. Use of experimental or investigational drugs, and/or participation in drug clinical studies within the 6 months prior to screening.
4. Use of immunosuppressive including Mitoxantrone (Novantrone®) or cytotoxic agents within 6 months prior to the screening visit.
5. Previous use of either of the following: natalizumab (Tysabri®), cladribine, laquinimod.
6. Previous treatment with glatiramer acetate (Copaxone®) Interferon-β (either 1a or 1b) or IVIG within 2 months prior to screening visit.
7. Systemic corticosteroid treatment of ≥30 consecutive days duration within 2 months prior to screening visit.
8. Previous total body irradiation or total lymphoid irradiation.
9. Previous stem cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation.
10. A known history of tuberculosis.
11. Acute infection two weeks prior to baseline visit.
12. Major trauma or surgery two weeks prior to baseline
13. A history of vascular thrombosis (excluding catheter-site superficial venous thrombophlebitis).
14. A carrier state of factor V Leiden mutation (either homo- or heterozygous) as disclosed at screening.
15. Positive screening test for Hepatitis B surface antigen, Hepatitis C antibody, or HIV antibody as disclosed at screening visit.
16. Use of potent inhibitors of CYP3A4 within 2 weeks prior to baseline visit (1 month for fluoxetine) see detailed list in Appendix 5
17. Use of amiodarone within 2 years prior to screening visit.
18. Pregnancy or breastfeeding.
19. Subjects with a clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation, as determined by medical history, physical examinations, ECG, laboratory tests or chest X-ray. Such conditions may include:

    * A cardiovascular or pulmonary disorder that cannot be well-controlled by standard treatment permitted by the study protocol.
    * A gastrointestinal disorder that may affect the absorption of study medication.
    * Renal or metabolic diseases.
    * Any form of chronic liver disease, including known non-alcoholic steatohepatitis.
    * A ≥2xULN serum elevation of either of the following at screening: ALT, AST or direct bilirubin
    * A QTC interval (obtained from either 2 ECG recordings at screening or from the mean value calculated from 3 measurements at baseline visit) which is \>450msec.
    * A family history of Long- QT syndrome.
    * A history of drug and/or alcohol abuse.
    * Major psychiatric disorder.
20. A known history of sensitivity to Gd.
21. Inability to successfully undergo MRI scanning.
22. Known drug hypersensitivity that would preclude administration of laquinimod, such as hypersensitivity to: mannitol, meglumine or sodium stearyl fumarate.

Exclusion Criteria:

1. Subjects who suffer from any form of progressive MS.
2. Any condition which the investigator feels may interfere with participation in the study.
3. Subjects with a clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation,
4. Subjects who received any investigational medication, immunosuppressives or cytotoxic agents within 6 months prior to screening
5. Previous treatment with immunomodulators within two months prior to screening
6. Pregnancy or breastfeeding.
D: Inclusion Criteria:

* Participation in study 28063.
* Completion of Week 36 visit of the core study 28063.
* Willingness and ability to comply with study procedures for the duration of the study.
* Voluntary provision of written informed consent (including, for the USA, subject authorization under the Health Insurance Portability and Accountability Act (HIPAA)), given before any study-related procedure that is not part of normal medical care and with the understanding that the subject may withdraw consent at any time without prejudice to his or her future medical care.

Exclusion Criteria:

* Premature discontinuation of core study 28063.
* Subjects who meet criteria listed below will receive IMP in study 28851:

  * Subjects who are eligible for participation in extension study 28851 but do not meet these criteria will not be treated with IMP but will undergo scheduled visits, irrespective of their treatment.
* All subjects must satisfy the following criteria before Extension Study Day 1 (D1-EXT; defined as the first day of dosing in the extension study) to be eligible for treatment with IMP:

  * Eligibility for participation in extension study 28851.
  * For women of childbearing potential, a negative urine pregnancy test at eligibility assessment.
  * Female subjects of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for four (4) weeks before the first dose administered within the extension study, during the study and for twelve (12) weeks after the last dose of trial medication. Adequate contraception is defined as two barrier methods, or one barrier method with spermicide, or an intrauterine device, or use of a combined oral female hormonal contraceptive (or the definitions requested by health authorities and locally amended in the core study 28063). For the purposes of this trial, women of childbearing potential are defined as: "All female subjects after puberty unless they are post-menopausal for at least two years or are surgically sterile" (For Germany Only: Female subjects of childbearing potential must be willing to avoid pregnancy by using highly effective methods of contraception for approximately four (4) weeks prior to D1-EXT, during and for twelve (12) weeks after the last dose of trial medication. This requirement does not apply to surgically sterile subjects or to subjects who are postmenopausal for at least 2 years. Highly effective contraception is defined as any method or combination of methods which result in a low failure rate (i.e. less than (\<) 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, sexual abstinence, vasectomized partner, 2 barrier methods, or 1 barrier method with spermicide)
* Willingness and ability to comply with study procedures for the duration of the study.
* To be eligible for treatment with investigational medicinal product (IMP) in study 28851, the subjects must not meet any of the following criteria:
* Non-eligibility for participation in extension study 28851 (premature discontinuation of core study 28063).
* Major protocol violation or non-compliance in the core study.
* Use of prohibited immunomodulatory / immunosuppressive therapies
* Serum immunoglobulin G (IgG) level \<3 gram per liter (g/L) if the subject received atacicept in the core study, or serum IgG level \<6 g/L if the subject received placebo in the core study (to protect the blinding of the core study, the IgG level will be communicated to the treating physician only if it is too low for extension study participation and only after all Week 36 assessments performed within the core study have been completed).
* Any condition, including laboratory findings that, in the opinion of the Investigator, constitutes a risk or a contraindication for participation in the extension study, or that could interfere with the study objectives, conduct or evaluation.
* Known active clinically significant acute or chronic infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives.
* Investigator judgement that treatment of the subject with atacicept in the extension study is not appropriate.
* Aspartate aminotransferase (AST), or alanine aminotransferase (ALT), or alkaline phosphatase (AP) level greater than (\>)2.5 x upper limit of normal (ULN), or total bilirubin \>1.5 x ULN at eligibility assessment.
* Clinically significant abnormality in any hematological test (e.g. hemoglobin \<100 g/L (6.21 millimoles per liter \[mmol/L\]), white blood cells \<3 x 10\^9 per liter (/L), platelets \<100 x 10\^9/L) at eligibility assessment.
* Clinically significant abnormality on electrocardiogram (ECG) performed at eligibility assessment.
* Presence of uncontrolled or New York Health Association (NYHA) class 3 or 4 congestive heart failure at Week 36 of the core study.
* Moderate to severe renal impairment (creatinine clearance \<50 milliliter per minute (mL/min) according to Cockcroft-Gault equation).
* Allergy or hypersensitivity to gadolinium (Gd).
* Allergy or hypersensitivity to atacicept or to any of the components of the formulated atacicept.
* Diagnosis or family history of Creutzfeldt-Jakob disease (CJD).

Answer: D