Atacicept in Multiple Sclerosis Extension Study, Phase II
Condition: Relapsing Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: Atacicept 25 mg; Atacicept 75 mg; Atacicept 150 mg; Atacicept 150 mg
Intervention description: Subjects who received atacicept 25 milligram (mg) subcutaneously (SC) as loading dose twice weekly for first 4 weeks, followed by atacicept 25 mg SC for 32 weeks, in 28063 study will continue with atacicept 25 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.; Subjects who received atacicept 75 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 75 mg SC for 32 weeks, in 28063 study will continued with atacicept 75 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.; Subjects who received atacicept 150 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 150 mg SC for 32 weeks, in 28063 study will continue with atacicept 150 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.; Subjects who received placebo SC twice weekly for first 4 weeks, followed by placebo SC for 32 weeks, in 28063 study will continue with atacicept 150 mg (without loading dose) SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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).