Atacicept in Multiple Sclerosis Extension Study, Phase II (ATAMS ext)

Merck KGaA (EMD Serono)

Status and phase: Terminated; Phase 2

Conditions: Relapsing Multiple Sclerosis

Treatments: Drug: Atacicept 150 mg; Drug: Atacicept 25 mg; Drug: Atacicept 75 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT00853762

28851

Details and patient eligibility

About

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.

Enrollment: 74 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

74 participants in 4 patient groups

Atacicept 25 mg (With Loading)

Experimental group

Treatment:

Drug: Atacicept 25 mg

Atacicept 75 mg (With Loading)

Experimental group

Treatment:

Drug: Atacicept 75 mg

Atacicept 150 mg (With Loading)

Experimental group

Treatment:

Drug: Atacicept 150 mg

Atacicept 150 mg (Without Loading)

Experimental group

Treatment:

Drug: Atacicept 150 mg