Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Four-Arm Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study to Evaluate the Safety, Tolerability and Efficacy as Assessed by Frequent MRI Measures of 3 Doses of Atacicept Monotherapy in Subjects With Relapsing Multiple Sclerosis (RMS) Over a 36 Week Treatment Course
Brief Summary: To evaluate the safety and tolerability of atacicept and to explore if atacicept reduces central nervous system inflammation in subjects with relapsing multiple sclerosis (RMS) as assessed by frequent magnetic resonance imaging (MRI). This study is randomised. Study medication is administered via subcutaneous (under the skin) injections.


Options:
A: 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.
B: Inclusion Criteria:

* Be between 18 and 60 years of age
* Have definite relapsing multiple sclerosis
* Have had one or more relapses within the prior 12 months
* Must be in a clinically stable or improving neurological state during the four weeks prior to Study Day 1
* Expanded Disability Status Scale (EDSS) score from 0 to 5.5, inclusive
* If female, she must either be post-menopausal or surgically sterilized; or use a hormonal contraceptive, intra uterine device, diaphragm with spermicide, or condom with spermicide, for the duration of the study; and be neither pregnant nor breast-feeding
* Confirmation that the subject is not pregnant must be established by a negative serum human chorionic gonadotropin (hCG) pregnancy test within 7 days of Study Day 1 and a negative urine pregnancy test on Study Day 1. A pregnancy test is not required if the subject is post-menopausal or surgically sterilized
* Be willing and able to comply with the protocol for the duration of the study
* Voluntarily provide written informed consent and, for USA sites only, a subject authorization under Health Insurance Portability and Accountability Act (HIPAA), prior to any study-related procedure that is not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care

Exclusion Criteria:

* Have secondary progressive multiple sclerosis (SPMS) or primary progressive MS (PPMS)
* Prior use of any interferon or glatiramer acetate
* Have had treatment with oral or systemic corticosteroids or adrenocorticotrophic hormone (ACTH) within 4 weeks of Study Day 1 and within 7 days prior to the Day 1 magnetic resonance imaging (MRI)
* Have a psychiatric disorder that is unstable or would preclude safe participation in the study.
* Have significant leukopenia (white blood cell count \< 0.5 times the lower limit of normal of the central laboratory) within 7 days of Study Day 1.
* Have elevated liver function tests (alanine aminotransferase \[AST\], aspartate aminotransferase \[ALT\], alkaline phosphatase \> 2.0 times the upper limit of normal \[ULN\] of the central laboratory, or total bilirubin \> 1.5 times the ULN of the central laboratory) within 7 days of Study Day 1 or a history of hepatitis (including infectious or drug-induced)
* Prior cytokine or anti-cytokine therapy within 3 months prior to Study Day 1
* Prior use of immunomodulatory or immunosuppressive therapy (including but not limited to cyclophosphamide, cyclosporin, methotrexate, azathioprine, linomide, mitoxantrone) within the 12 months prior to Study Day 1
* Prior use of cladribine or have received total lymphoid irradiation
* Have allergy or hypersensitivity to human serum albumin, mannitol, glatiramer acetate, natural or recombinant interferon-β, or any other components of the study drugs or gadolinium diethylenetriaminepentaacetic acid
* Have taken intravenous immunoglobulin or any other investigational drug or taken part in any experimental procedure in the 6 months prior to Study Day 1.
* Presence of systemic disease that might interfere with subject safety, compliance or evaluation of the condition under study (e.g. insulin-dependent diabetes, Lyme disease, clinically significant cardiac disease, human immunodeficiency virus \[HIV\], human T-cell lymphotrophic virus type I \[HTLV-1\])
* Have had plasma exchange in 3 months prior to Study Day 1.
C: Inclusion Criteria:

- Diagnosis of RMS (as per McDonald criteria, 2005) Other protocol-defined inclusion criteria could apply.

Exclusion Criteria:

* Have primary progressive multiple sclerosis (MS)
* Have secondary progressive MS without superimposed relapses
* Relevant cardiac, hepatic and renal diseases as specified in the protocol
* Pretreatment with immunosuppressants and immunomodulating drugs as specified in the protocol
* Clinical significant abnormalities in blood cell counts and immunoglobulin levels as specified in the protocol
* Clinical significant acute or chronic infections as specified in the protocol Other protocol-defined exclusion criteria could apply.
D: Inclusion Criteria:

* Female and male patients
* Aged 18-55 years
* Diagnosis of RRMS (Relapsing-Remitting Multiple Sclerosis), EDSS score of 0 to 5.0
* Treatment-naive to IFNB or Copaxone

Exclusion Criteria:

* Neurological progression at disease onset or between relapses
* Serious or acute heart diseases
* History of severe depression or suicide attempt
* Serious or acute liver, renal or bone marrow dysfunction
* Monoclonal gammopathy
* Known allergy to Gadolinium-DTPA, to IFNs (Interferons), to glatiramer acetate, to human albumin or to mannitol
* Pregnancy or lactation

Answer: C