A four-arm randomised, double-blind, placebo-controlled, multicentre Phase II study to evaluate the safety, tolerability and efficacy as assessed by frequent MRI measures of three doses of atacicept monotherapy in subjects with relapsing multiple sclerosis (RMS) over a 36 weeks treatment course. - Atacicept frequent MRI study in RMS

• Register: EUCTR
• Last refreshed on: 12 June 2012
• Main ID: EUCTR2007-003936-50-SE
• Date of registration: 03/03/2008
• Prospective Registration: Yes
• Primary sponsor: Merck Serono Geneva- an affiliate of Merck KGaA, Darmstadt Germany
• Public title: A four-arm randomised, double-blind, placebo-controlled, multicentre Phase II study to evaluate the safety, tolerability and efficacy as assessed by frequent MRI measures of three doses of atacicept monotherapy in subjects with relapsing multiple sclerosis (RMS) over a 36 weeks treatment course. - Atacicept frequent MRI study in RMS
• Scientific title: A four-arm randomised, double-blind, placebo-controlled, multicentre Phase II study to evaluate the safety, tolerability and efficacy as assessed by frequent MRI measures of three doses of atacicept monotherapy in subjects with relapsing multiple sclerosis (RMS) over a 36 weeks treatment course. - Atacicept frequent MRI study in RMS
• Date of first enrolment: 02/04/2008
• Target sample size: 255
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-003936-50
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Czech Republic, France, Lithuania, Netherlands, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Diagnosis of Relapsing Multiple Sclerosis (per McDonald criteria, 2005);
2. Fulfil at least one of the following: two or more documented relapses during the previous 2 years, one or more documented relapses in the year before enrolment, or one or more Gd- enhancing lesions detected on MRI at screening.
3. Male or female between 18-60 years old, inclusive at the time the informed consent is obtained.
4. Have an EDSS from 0 5.5, inclusive;
5. Women of childbearing potential must not be breast feeding and have a negative serum/urine pregnancy test at initial screening and at Study Day 1 (SD1) before dosing. For the purposes of this trial, a woman of childbearing potential is defined as: “All female subjects after puberty unless they are post-menopausal for at least two years, or are surgically sterile”.
6. Female subjects of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for approximately four (4) weeks prior to SD1, 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. Adequate contraception is defined as two barrier methods, or one barrier method with spermicide, or intrauterine device or use of the oral female contraceptive;
7. Subject is willing and able to comply with study procedures for the duration of the study;
8. Voluntarily provide written informed consent (obtained before any trial related procedure), including, for USA, subject authorization under Health Insurance Portability and Accountability Act (HIPAA), prior to 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 their future medical care.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Have primary progressive MS.
2. Have secondary progressive MS without superimposed relapses.
3. Any condition, including laboratory findings and findings in the medical history or in the pre-study assessments, that in the opinion of the Investigator, constitute a risk or a contraindication for the participation in the study or that could interfere with the study objectives, conduct or evaluation.
4. Prior treatment with B cell modulating therapies, such as rituximab or belimumab.
5. Exposure to immunomodulatory therapy, such as interferon beta or glatiramer acetate, within 3 months prior to SD1.
6. Discontinuation of prior immunodulatory therapy due to perceived lack of efficacy.
7. Prior exposure to immunosuppressive or cytotoxic agents including but not restricted to cladribine, mitoxantrone, alemtuzumab cyclophosphamide, azathioprine, methotrexate, natalizumab or mycophenolate mofetil.
8. Prior myelosuppressive / cytotoxic therapy, such as lymphoid irradiation, or bone marrow transplantation.
9. Prior use of cytokine or anti-cytokine therapy, intravenous immunoglobulin (IVIg) or plasmapheresis within 6 months prior to SD1.
10. Treatment with oral or systemic corticosteroids or adrenocorticotropic hormone within 28 days prior to SD1.
11. Require chronic or monthly pulse corticosteroids during the study
12. Participation in any interventional clinical trial within 2 months prior to SD1, or within 5 half-lives of the investigated compound, whichever is longer.
13. Allergy or hypersensitivity to atacicept or to any of the components of the formulated atacicept.
14. Diagnosis or family history of Creutzfeldt-Jakob disease (CJD).
15. Moderate to severe renal impairment (creatinine clearance <50ml/min according to Cockcroft-Gault equation).
16. Allergy or hypersensitivity to gadolinium.
17. History or presence of uncontrolled or New York Health Association (NYHA) class 3 or 4 congestive heart failure.
18. History of cancer, except adequately treated basal cell carcinoma of the skin, cervical dysplasia or carcinoma in situ of the skin or the cervix.
19. Aspartate aminotransferase (AST) alanine aminotransferase (ALT) or alkaline phosphatase (AP) level >2.5 x ULN. Total bilirubin >1.5 x ULN at screening.
20. Clinically significant abnormality in any haematological test (e.g. haemoglobin <100 g/L (6,21 mmol/L), WBC <3*109/L, lymphocytes <0.8*109/L, platelets <140*109/L) at screening.
21. Clinically significant abnormality on chest X-ray performed within 3 months prior to SD1 or on ECG performed at screening.
22. Immunisation with live vaccines within one month prior to SD1 or need for such treatment during the study.
23. Known active clinically significant acute or chronic infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks of SD1
24. Positive HIV, hepatitis C or hepatitis B (HBsAg and HBc antibody) serology (test performed at screening).
25. Presence of active or latent tuberculosis within the past year prior to screening. Subjects should be evaluated and screened for active or latent tuberculosis according to national and/or local recommendations
26. Serum IgG below 6 g/L at screening




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Relapsing multiple sclerosis
MedDRA version: 9.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis

Intervention(s)

Product Name: atacicept
Pharmaceutical Form: Solution for injection
INN or Proposed INN: atacicept
Other descriptive name: TACI-Fc5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-
INN or Proposed INN: atacicept
Other descriptive name: TACI-Fc5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 75-
INN or Proposed INN: atacicept
Other descriptive name: TACI-Fc5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: - Evaluate safety and tolerability of three doses of atacicept in subjects with RMS, including incidence and severity of infections.
- Evaluate three doses of atacicept in order to determine a minimally effective dose (MED) in subjects with RMS.

Primary end point(s): The primary endpoint is the mean number of T1 gadolinium (Gd)-enhancing lesions per subject per scan from week 12 to 36, inclusive.

Main Objective: The primary objective of the study is to evaluate the efficacy of three doses of atacicept to reduce CNS inflammation in subjects with RMS as assessed by frequent MRI.

Secondary ID(s)

2007-003936-50-ES

28063