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.
- Conditions
- MS10007951
- Registration Number
- NL-OMON33672
- Lead Sponsor
- Merck Serono the Netherlands - a division of Merck BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 7
All subjects must satisfy the following entry criteria prior to baseline/SD1 (the first
day of dosing):
1. Diagnosis of Relapsing Multiple Sclerosis (per McDonald criteria, 2005);
2. Fulfill 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, 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.
To be eligible for inclusion in this study the subjects must not satisfy any of the
following 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, mycophenolate mofetil, azathioprine, methotrexate, or natalizumab.
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 Please add definition.
[NYHA class 3: Cardiac disease resulting in marked limitation of physical activity. Subjects are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnoea, or anginal pain.
NYHA class 4: Cardiac disease resulting in inability to carry on any physical activity without discomfort.
Symptoms of heart failure or the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased. (Source: The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9th ed. Boston,
Mass: Little, Brown & Co; 1994:253-256.)];
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 w
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• The primary endpoint is the mean number of T1 gadolinium (Gd)-enhancing<br /><br>lesions per subject per scan from week 12 to 36, inclusive.</p><br>
- Secondary Outcome Measures
Name Time Method