A phase II, multicenter, randomized, double-blind, placebo-controlled, safety, tolerability and efficacy study of add-on Cladribine tablet therapy with Rebif New Formulation in Multiple Scleroris Subjects with Active Disease - Phase II Cladribine add-on to Rebif New Formulation in MS subjects with active disease

• Register: EUCTR
• Last refreshed on: 3 September 2012
• Main ID: EUCTR2006-003366-33-IT
• Date of registration: 08/01/2008
• Prospective Registration: Yes
• Primary sponsor: MERCK SERONO INTERNATIONAL SA
• Public title: A phase II, multicenter, randomized, double-blind, placebo-controlled, safety, tolerability and efficacy study of add-on Cladribine tablet therapy with Rebif New Formulation in Multiple Scleroris Subjects with Active Disease - Phase II Cladribine add-on to Rebif New Formulation in MS subjects with active disease
• Scientific title: A phase II, multicenter, randomized, double-blind, placebo-controlled, safety, tolerability and efficacy study of add-on Cladribine tablet therapy with Rebif New Formulation in Multiple Scleroris Subjects with Active Disease - Phase II Cladribine add-on to Rebif New Formulation in MS subjects with active disease
• Date of first enrolment: 30/10/2008
• Target sample size: 260
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-003366-33
• 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

Italy, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1. be male or female 18-55 years of age (inclusive) 2. weight between 40-120 kg inclusive 3. have definite MS as confirmed by the revised McDonald criteria (Polman et al 2005) and have relapsing forms of MS, such as relapsing remitting or secondary progressive type of disease with superimposed relapses forms (See Appendix I) 4. have experienced at leaset one relapse while receiving Rebif for at least 48 weeks prior to Screening 5. be clinically stable (other than an MS relapse) during the 28 days preceding Screening 6. have an EDSS from 1.0-5.5 inclusive (see appendi x d) 7. have not received more than one DMD other than Rebif during MS treatment history 8. have no prior exposure to immunosuppressive or cytotoxic agents 9. if female must either: a) be post menopausal or surgically sterilized or b) use a hjormonal contraceptive, intra-uterine device, dikaphragm with spermicide, or condom with spermicide, for the duration of the study and c) be neither pregnant nor breast-feeding nor attempting to conceive 10. if male must be willing to use contraception to avoid pregnancies 11. be willing and able to comply with study procedures for the duration of the study 12. have not met any of the exclusion criteria outlined in this protocol; 13. voluntarily provide written informed consent,including, for USAS, subject authroization ujnder Health Insurance Portability and Accountability Act (HIPAA), prior to any study related procedure that i not part of normal medical care, and with the understanding that the subject may withdraw consend 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 or secondary progressive MS without relapse forms; 2. have prior or current malignancy; 3. have a history of chronic or clinically significant hematologic abnormalities; 4. have platelet, absolute neutrophil or absolute lymphocyte counts below the lower limit of normal range or significant leukopenia (white blood cell count < 0.5 times the lower limit of normal of the central laboratory) withing 28 days prior to Study Day 1; 5. prior use of cladribine, mitoxantrone, campath-1h, cyclophosphamide, azathioprine, methotrexate, natalizumab, lymphoid irradiation, bone marrow transplantation or myelosuppressive/cytotoxic therapy; 6. use of cytokine or anti-cytokine therapy, intravenous immunoglobulin (IVIC) or plasmapheresis within 3 months prior to Study Day 1; 7. treatment with oral or systemic corticosteroids or adrenocorticotropic hormone within 28 days prior to Study Day 1; 8. subjects requires chronic or monthly pulse corticosteroids during the study; 9. use of any investigational drug or experimental procedure within 6 months prior to Study Day 1; 10. Subject has inadequate liver function, defined by a total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phsphatase 2.5 times the upper limit of the normal values; 11. subejct suffers from major medical or psychiatric illness that in the opinion of the investigator creates undue risk to the subject or could affect compliance with the study protocol; 12. have compromised immune function (eg HIV+) or ongoing infection; 13. have an allergy or hypersensitivity to gadolinium, to cladribine or any of its excipients, or Rebif or any of its excipient(s)


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

Health Condition(s) or Problem(s) studied

MULTIPLE SCLEROSIS
MedDRA version: 9.1 Level: LLT Classification code 10028245 Term: Multiple sclerosis

Intervention(s)

Trade Name: REBIF*SC 12SIR 12000000UI44MCG
Pharmaceutical Form: Solution for injection
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 44-

Pharmaceutical Form: Tablet
INN or Proposed INN: Cladribine
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: Assess the efficacy in MS subjects with active disease of 2 cladribine tablet dose levels as an add-on to a fixed dose of Rebif (44 mcg tiw) compared to placebo as an add-on to a fixed dose of Rebif on: - lesion activity (as measured by MRI) - qualifying relapse rate - progression of disability

Primary end point(s): The primary safety endpoints will consist of safety and tolerability parameters measured over a period of 96 weeks

Main Objective: Evaluate the safety and tolerability of oral cladribine (cladribine tablets)when added on to Rebif. Evaluate the efficacy of oral cladribine (cladribine tablets) when added on to Rebif compared to placebo when added on to Rebif in MS subjects with active disease

Secondary ID(s)

26593