Atacicept in Multiple Sclerosis Extension Study, Phase II

Relapsing Multiple Sclerosis Clinical Trial

— ATAMS ext  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00853762
• Other study ID #: 28851
• Status: Terminated
• Phase: Phase 2
• First received: February 26, 2009
• Last updated: February 3, 2012
• Start date: February 2009
• Est. completion date: February 2011

Study information

• Verified date: February 2012
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 68
• Est. completion date: February 2011
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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).

Study Design

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Relapsing Multiple Sclerosis
• Sclerosis

Intervention

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).
• Atacicept
Best benefit / risk ratio treatment of Atacicept dose that has been identified

Locations

Country	Name	City	State
Australia	Research Site	Box Hill VIC
Australia	Research Site	Fitzroy
Australia	Research Site	New Lambton
Australia	Research Site	Woodville
Belgium	Research Site	Diepenbeek
Belgium	Research Site	Sijsele
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Ottawa	Ontario
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Hradec Králové
France	Research Site	Caen
France	Research Site	Saint-Herblain
Germany	Research Site	Bochum
Germany	Research Site	Düsseldorf
Lebanon	Research Site	Beyrouth
Lithuania	Research Site	Kaunas
Netherlands	Research Site	Breda
Netherlands	Research Site	Nieuwegein
Netherlands	Research Site	Rotterdam
New Caledonia	Research Site	Winston Salem
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Samara
Russian Federation	Research Site	Vladimir
Russian Federation	Research Site	Yaroslavl
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Sweden	Research Site	Stockholm
Switzerland	Research Site	Basel
Switzerland	Research Site	Innsbruck
Switzerland	Research Site	Zürich
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Odessa
Ukraine	Research Site	Uzhgorod
United Kingdom	Research Site	London
United Kingdom	Research Site	Sheffield
United Kingdom	Research Site	Stoke on Trent
United States	Research Site	Cleveland	Ohio
United States	Research Site	Cleveland,	Ohio
United States	Research Site	East Lansing	Michigan
United States	Research Site	Nashville	Tennessee
United States	Research Site	Northbrook	Illinois
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Stie	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
EMD Serono

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czech Republic,  France,  Germany,  Lebanon,  Lithuania,  Netherlands,  New Caledonia,  Russian Federation,  Spain,  Sweden,  Switzerland,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nature and severity of AEs and SAEs (i.e. infections, injection site reactions and malignancies) at each visit		At each visit	No
Primary	Hematology, and blood chemistry laboratory parameters and vital signs at each visit		At each visit	No
Primary	ECGs		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	No
Primary	IgG levels (i.e. IgG level <3 g/L)		Will be monitored for the duration of the study	No
Primary	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		At each study visit	No
Secondary	Number of clinical attacks/relapses for duration of study		Duration of study	No
Secondary	EDSS and KFS scores		At W12, W36, 1x per year starting at W60, Early Study Termination (EST) and Early Treatment Termination (ETT) visits	No
Secondary	MSFC score		At W12, W36, once per year starting at W60, EST and ETT visits	No
Secondary	MRI parameters		At W12, once per year starting at W60, W228 and possibly at EST and ETT visits	No
Secondary	PK measures		At W12, W36, W60, W216, W228 and at EST or ETT visit	No
Secondary	PD measures		At each visit	No
Secondary	Pharmacogentics/pharmacogenomics analysis in a subgroup of patients		At W12 and 1x per year from W60	No