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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00853762




Registration number
NCT00853762
Ethics application status
Date submitted
26/02/2009
Date registered
2/03/2009
Date last updated
20/03/2017

Titles & IDs
Public title
Atacicept in Multiple Sclerosis Extension Study, Phase II
Scientific 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)
Secondary ID [1] 0 0
28851
Universal Trial Number (UTN)
Trial acronym
ATAMS ext
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsing Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atacicept 25 mg
Treatment: Drugs - Atacicept 75 mg
Treatment: Drugs - Atacicept 150 mg
Treatment: Drugs - Atacicept 150 mg

Experimental: Atacicept 25 mg (With Loading) -

Experimental: Atacicept 75 mg (With Loading) -

Experimental: Atacicept 150 mg (With Loading) -

Experimental: Atacicept 150 mg (Without Loading) -


Treatment: Drugs: Atacicept 25 mg
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.

Treatment: Drugs: Atacicept 75 mg
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.

Treatment: Drugs: Atacicept 150 mg
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.

Treatment: Drugs: Atacicept 150 mg
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity
Timepoint [1] 0 0
From the first dose of study drug administration up to Week 24
Primary outcome [2] 0 0
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Timepoint [2] 0 0
Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36
Primary outcome [3] 0 0
Change From Baseline in Vital Signs: Pulse Rate
Timepoint [3] 0 0
Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36
Primary outcome [4] 0 0
Change From Baseline in Vital Signs: Temperature
Timepoint [4] 0 0
Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36
Primary outcome [5] 0 0
Change From Baseline in Electrocardiogram (ECGs)
Timepoint [5] 0 0
Baseline, Week 12 and 36
Primary outcome [6] 0 0
Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels
Timepoint [6] 0 0
Baseline up to Week 36
Primary outcome [7] 0 0
Number of Subjects With Positive Neutralizing Antibody (NAb)
Timepoint [7] 0 0
Baseline, Week 12 and 36
Secondary outcome [1] 0 0
Number of Subjects With Clinical Attacks/Relapses
Timepoint [1] 0 0
Baseline up to Week 24
Secondary outcome [2] 0 0
Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Week 12
Timepoint [2] 0 0
Baseline, Week 12
Secondary outcome [3] 0 0
Change in Multiple Sclerosis Functional Composite (MSFC) Score at Week 12
Timepoint [3] 0 0
Week 12
Secondary outcome [4] 0 0
Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject
Timepoint [4] 0 0
Baseline, Week 12 and 24
Secondary outcome [5] 0 0
Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject
Timepoint [5] 0 0
Baseline, Week 12 and Week 24
Secondary outcome [6] 0 0
Concentrations of Free and Total Atacicept
Timepoint [6] 0 0
Baseline and Week 12
Secondary outcome [7] 0 0
Free B-Lymphocyte Stimulator (BLyS) and Free A Proliferation-Inducing Ligand (APRIL) Serum Concentrations.
Timepoint [7] 0 0
Baseline, Week 12 and 36
Secondary outcome [8] 0 0
Pharmacogenetics/Pharmacogenomics Analysis
Timepoint [8] 0 0
Day 1 and Week 36

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2011
Sample size
Target
Accrual to date
Final
74
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Box Hill VIC
Recruitment hospital [2] 0 0
Research Site - Fitzroy
Recruitment hospital [3] 0 0
Research Site - New Lambton
Recruitment hospital [4] 0 0
Research Site - Woodville
Recruitment postcode(s) [1] 0 0
- Box Hill VIC
Recruitment postcode(s) [2] 0 0
- Fitzroy
Recruitment postcode(s) [3] 0 0
- New Lambton
Recruitment postcode(s) [4] 0 0
- Woodville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
Belgium
State/province [7] 0 0
Diepenbeek
Country [8] 0 0
Belgium
State/province [8] 0 0
Sijsele
Country [9] 0 0
Canada
State/province [9] 0 0
Alberta
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Czech Republic
State/province [11] 0 0
Brno
Country [12] 0 0
Czech Republic
State/province [12] 0 0
Hradec Králové
Country [13] 0 0
France
State/province [13] 0 0
Caen
Country [14] 0 0
France
State/province [14] 0 0
Saint-Herblain
Country [15] 0 0
Germany
State/province [15] 0 0
Bochum
Country [16] 0 0
Germany
State/province [16] 0 0
Düsseldorf
Country [17] 0 0
Lebanon
State/province [17] 0 0
Beyrouth
Country [18] 0 0
Lithuania
State/province [18] 0 0
Kaunas
Country [19] 0 0
Netherlands
State/province [19] 0 0
Breda
Country [20] 0 0
Netherlands
State/province [20] 0 0
Nieuwegein
Country [21] 0 0
Netherlands
State/province [21] 0 0
Rotterdam
Country [22] 0 0
New Caledonia
State/province [22] 0 0
Winston Salem
Country [23] 0 0
Russian Federation
State/province [23] 0 0
Ekaterinburg
Country [24] 0 0
Russian Federation
State/province [24] 0 0
Moscow
Country [25] 0 0
Russian Federation
State/province [25] 0 0
Novosibirsk
Country [26] 0 0
Russian Federation
State/province [26] 0 0
Saint Petersburg
Country [27] 0 0
Russian Federation
State/province [27] 0 0
Samara
Country [28] 0 0
Russian Federation
State/province [28] 0 0
Vladimir
Country [29] 0 0
Russian Federation
State/province [29] 0 0
Yaroslavl
Country [30] 0 0
Spain
State/province [30] 0 0
Barcelona
Country [31] 0 0
Spain
State/province [31] 0 0
Madrid
Country [32] 0 0
Spain
State/province [32] 0 0
Malaga
Country [33] 0 0
Sweden
State/province [33] 0 0
Stockholm
Country [34] 0 0
Switzerland
State/province [34] 0 0
Basel
Country [35] 0 0
Switzerland
State/province [35] 0 0
Innsbruck
Country [36] 0 0
Switzerland
State/province [36] 0 0
Zürich
Country [37] 0 0
Ukraine
State/province [37] 0 0
Kharkiv
Country [38] 0 0
Ukraine
State/province [38] 0 0
Kyiv
Country [39] 0 0
Ukraine
State/province [39] 0 0
Odessa
Country [40] 0 0
Ukraine
State/province [40] 0 0
Uzhgorod
Country [41] 0 0
United Kingdom
State/province [41] 0 0
London
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Sheffield
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Stoke on Trent

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
EMD Serono
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck KGaA, Darmstadt, Germany
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00853762
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Daniel Mikol, MD, PhD
Address 0 0
EMD Serono
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00853762