Clinical trial NCT00853762: Atacicept in Multiple Sclerosis Extension Study, Phase II
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Relapsing Multiple Sclerosis
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2009-03-02
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity
timeFrame: From the first dose of study drug administration up to Week 24
measure: Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36
measure: Change From Baseline in Vital Signs: Pulse Rate
timeFrame: Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36
measure: Change From Baseline in Vital Signs: Temperature
timeFrame: Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36
measure: Change From Baseline in Electrocardiogram (ECGs)
timeFrame: Baseline, Week 12 and 36
measure: Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels
timeFrame: Baseline up to Week 36
measure: Number of Subjects With Positive Neutralizing Antibody (NAb)
timeFrame: Baseline, Week 12 and 36
Secondary outcomes:
measure: Number of Subjects With Clinical Attacks/Relapses
timeFrame: Baseline up to Week 24
measure: Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Week 12
timeFrame: Baseline, Week 12
measure: Change in Multiple Sclerosis Functional Composite (MSFC) Score at Week 12
timeFrame: Week 12
measure: Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject
timeFrame: Baseline, Week 12 and 24
measure: Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject
timeFrame: Baseline, Week 12 and Week 24
measure: Concentrations of Free and Total Atacicept
timeFrame: Baseline and Week 12
measure: Free B-Lymphocyte Stimulator (BLyS) and Free A Proliferation-Inducing Ligand (APRIL) Serum Concentrations.
timeFrame: Baseline, Week 12 and 36
measure: Pharmacogenetics/Pharmacogenomics Analysis
timeFrame: Day 1 and Week 36
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Northbrook
country: United States
facility: Research Site
state: Illinois
city: East Lansing
country: United States
facility: Research Site
state: Michigan
city: Cleveland,
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Box Hill VIC
country: Australia
facility: Research Site
city: Fitzroy
country: Australia
facility: Research Site
city: New Lambton
country: Australia
facility: Research Site
city: Woodville
country: Australia
facility: Research Site
city: Diepenbeek
country: Belgium
facility: Research Site
city: Sijsele
country: Belgium
facility: Research Site
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Brno
country: Czech Republic
facility: Research Site
city: Hradec Králové
country: Czech Republic
facility: Research Site
city: Caen
country: France
facility: Research Site
city: Saint-Herblain
country: France
facility: Research Site
city: Bochum
country: Germany
facility: Research Site
city: Düsseldorf
country: Germany
facility: Research Site
city: Beyrouth
country: Lebanon
facility: Research Site
city: Kaunas
country: Lithuania
facility: Research Site
city: Breda
country: Netherlands
facility: Research Site
city: Nieuwegein
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Winston Salem
country: New Caledonia
facility: Research Site
city: Ekaterinburg
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Samara
country: Russian Federation
facility: Research Site
city: Vladimir
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Basel
country: Switzerland
facility: Research Site
city: Innsbruck
country: Switzerland
facility: Research Site
city: Zürich
country: Switzerland
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Odessa
country: Ukraine
facility: Research Site
city: Uzhgorod
country: Ukraine
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Sheffield
country: United Kingdom
facility: Research Site
city: Stoke on Trent
country: United Kingdom
facility: Research Site
Study officials:
affiliation: EMD Serono
name: Daniel Mikol, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Kappos L, Hartung HP, Freedman MS, Boyko A, Radu EW, Mikol DD, Lamarine M, Hyvert Y, Freudensprung U, Plitz T, van Beek J; ATAMS Study Group. Atacicept in multiple sclerosis (ATAMS): a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Neurol. 2014 Apr;13(4):353-63. doi: 10.1016/S1474-4422(14)70028-6. Epub 2014 Mar 6.