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

This study has been terminated.
(EMD Serono voluntarily decided to terminate this trial after observing increased MS disease activity in trial 28063 ATAMS [Please refer to ATAMS])
Sponsor:
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT00853762
First received: February 26, 2009
Last updated: February 3, 2012
Last verified: February 2012
  Purpose

This study, 28851, is a long-term follow-up study of subjects enrolled in ATAMS study 28063, the aim of which 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 sub cutaneously (under the skin). Subjects randomized to placebo in ATAMS will receive atacicept at 150 mg once a week sub cutaneously 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 intial and part A treatment allocation/dose.


Condition Intervention Phase
Relapsing Multiple Sclerosis
Drug: Atacicept
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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)

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Nature and severity of AEs and SAEs (i.e. infections, injection site reactions and malignancies) at each visit [ Time Frame: At each visit ] [ Designated as safety issue: No ]
  • Hematology, and blood chemistry laboratory parameters and vital signs at each visit [ Time Frame: At each visit ] [ Designated as safety issue: No ]
  • ECGs [ Time Frame: At SD 1, W12, W36, once per year starting at W60, and at long term follow up, early study termination and early treatment termination visits ] [ Designated as safety issue: No ]
  • IgG levels (i.e. IgG level <3 g/L) [ Time Frame: Will be monitored for the duration of the study ] [ Designated as safety issue: No ]
  • Immunogenicity: development of NAb to atacicept, persistence of NAb in subjects who become NAb-positive either in the core study or in the extension study will be assessed at each study visit at each study visit [ Time Frame: At each study visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of clinical attacks/relapses for duration of study [ Time Frame: Duration of study ] [ Designated as safety issue: No ]
  • EDSS and KFS scores [ Time Frame: At W12, W36, 1x per year starting at W60, Early Study Termination (EST) and Early Treatment Termination (ETT) visits ] [ Designated as safety issue: No ]
  • MSFC score [ Time Frame: At W12, W36, once per year starting at W60, EST and ETT visits ] [ Designated as safety issue: No ]
  • MRI parameters [ Time Frame: At W12, once per year starting at W60, W228 and possibly at EST and ETT visits ] [ Designated as safety issue: No ]
  • PK measures [ Time Frame: At W12, W36, W60, W216, W228 and at EST or ETT visit ] [ Designated as safety issue: No ]
  • PD measures [ Time Frame: At each visit ] [ Designated as safety issue: No ]
  • Pharmacogentics/pharmacogenomics analysis in a subgroup of patients [ Time Frame: At W12 and 1x per year from W60 ] [ Designated as safety issue: No ]

Enrollment: 68
Study Start Date: February 2009
Study Completion Date: February 2011
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A

Part A - double blind

Arm 1 - Low dose treatment of Atacicept 25 mg once a week

Arm 2 - Mid-dose treatment of Atacicept 75 mg once a week

Arm 3 - High-dose treatment of Atacicept 150 mg once a week

Drug: Atacicept
During Part A subjects will continue to receive the atacicept dose to which they have been randomized in study 28063 (ATAMS) i.e. 25mg once a week (QW) subcutaneously (SC), 75mg QW SC or 150mg QW SC. Subjects randomized to placebo in ATAMS will receive atacicept 150mg QW SC without loading dose. 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). The study treatment period will be up to five years starting from first administration of the first dose of atacicept from the core study (28063 - ATAMS).
Experimental: B

Part B - open label

Arm 1 - Best benefit / risk ratio treatment of Atacicept dose that has been identified

Drug: Atacicept
Best benefit / risk ratio treatment of Atacicept dose that has been identified

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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, two barrier methods, or one barrier method with spermicide)
  • Willingness and ability to comply with study procedures for the duration of the study.
  • To be eligible for treatment with 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 IgG level <3 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 judgment 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 >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 mmol/L), white blood cells <3 x 109/L, platelets <100 x 109/L) at eligibility assessment.
  • Clinically significant abnormality on 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 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00853762

  Show 48 Study Locations
Sponsors and Collaborators
EMD Serono
Investigators
Study Director: Daniel Mikol, MD, PhD EMD Serono
  More Information

No publications provided

Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00853762     History of Changes
Other Study ID Numbers: 28851
Study First Received: February 26, 2009
Last Updated: February 3, 2012
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on September 22, 2014