E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | Relapse-remitting Multiple Sclerosis (RRMS) | |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Classification code | 10048393 | |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial | The primary objective of this study is to assess the dose-response effect of multiple subcutaneous (SC) injections of CNTO 1275 in subjects with RRMS based on the cumulative number of new gadolinium (Gd)-enhancing T1-weighted lesions on cranial MRIs through week 23. | |
E.2.2 | Secondary objectives of the trial | The secondary objectives of this study are to assess the clinical response and safety of multiple SC injections of CNTO 1275 and to describe the pharmacokinetics after repeated doses of CNTO 1275 in subjects with RRMS. | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria | 1. Be >/= 18 and </= 65 years of age at screening. 2. Have a definite diagnosis of RRMS according to the 2001 Guidelines from the International Panel on the Diagnosis of MS (McDonald at al, 2001). 3. Have a Kurtzke’s EDSS Scale score of 0 to 6.5 (described in Appendix B of the protocol). 4. Have a history of at least 1 of the following: * A minimum of 2 relapses of MS within the previous 2 years but not within the 1-month period prior to screening. * A relapse of MS within the previous 6 months but not within the 1-month period prior to screening. 5. Women of childbearing potential and men must be using adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device [IUD], barrier method with spermicide, or surgical sterilization) during the study and must agree to continue such precautions for 1 year after receiving the last injection(s) of study agent. Women of childbearing potential must test negative for pregnancy at screening. 6. Are considered eligible according to county–specific TB screening guidelines for latent TB defined in Section 4.3. of the protocol. 7. Are capable of providing written informed consent, which must be obtained prior to any study-related procedures. 8. Are able to adhere to the study visit schedule and understand and comply with other protocol requirements. | |
E.4 | Principal exclusion criteria | 1. Have a CNS disease (eg, CNS lymphoma, systemic lupus erythematous) that could affect the interpretation of the functional disability scale scores. 2. Have significant bulbar involvement of MS or other neurologic deficits or history that would, in the judgment of the investigator, place the subject at significant risk of infectious complications. 3. Have a decubitus ulcer. 4. Have an indwelling foley catheter. 5. Have received any immunomodulating therapies (eg, interferon) within the 3-month period prior to screening. 6. Have received glatiramer acetate within the 3-month period prior to screening. 7. Have ever received cladribine or any chemotherapeutic agents (eg, mitoxantrone). 8. Have received systemic corticosteroids within the 1-month period prior to screening. 9. Have received any previous treatment with CNTO 1275 or any other investigational agent for the treatment of MS that is known to target IL-12 or IL-23. 10. Have received treatment in a clinical study within 3 months prior to screening or within 5 half-lives (if known) of an investigational agent, whichever is longer. The Sponsor may grant inclusion approval on an individual basis if it is determined unlikely that the investigational agent would have an effect on MRI lesions during the screening or treatment period. 11. Are pregnant, nursing, or planning pregnancy (both men and women) within 1 year after the last study agent injection(s). 12. Have a history of a previous immediate hypersensitivity response including anaphylaxis or a severe allergic reaction to monoclonal antibodies. 13. Have a chest x-ray at screening or within 2 months prior to screening that shows evidence of malignancy, infection, or any abnormalities suggestive of TB as described in Section 4.3.2. of the protocol. 14. Have laboratory evidence of any of the following: * Hemoglobin < 8.0 gm/dL * WBC count < 3.0 x 1,000,000,000 cells/L * Neutrophil count < 1.5 x 1,000,000,000 cells/L * Platelet count < 100 x 1,000,000,000 cells/L * Serum transaminase levels > 1.5 times the upper limit of normal for the clinical laboratory * Serum creatinine levels > twice the upper limit of the normal reference rangefor the clinical laboratory, unless calculated creatinine clearance is > 30mL/min. 15. Have a serious infection (eg, hepatitis, pneumonia or pyelonephritis), a chronic or serious recurring infection, hospitalization for infection, or treatment with IV antibiotics for infection within 2 months prior to screening. Less serious infections (eg, acute upper respiratory tract infection or uncomplicated urinary tract infection) need not be considered exclusions at the discretion of the investigator. 16. Have or have had opportunistic infections (eg, cytomegalovirus [CMV], Pneumocystis carinii, histoplasmosis or any mycobacterial infection other than TB) within 6 months prior to randomization. 17. Have a known or suspected diagnosis of asthma. 18. Have documented current or past infection with hepatitis B or C. 19. Have documented human immunodeficiency virus (HIV) infection. 20. Have presence of a transplanted organ (with the exception of a corneal transplant performed > 3 months prior to randomization). 21. Have a known malignancy or history of malignancy within the previous 5 years (with the exception of basal cell carcinoma of the skin that has been treated with no evidence of recurrence). 22. Have a history of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease. 23. Have a history of alcohol or substance abuse within the preceding 6 months that, in the opinion of the investigator, may increase the risks associated with study participation, or study agent administration, or may interfere with interpretation of results. 24. Are considered ineligible according to the country-specific TB screening guidelines for latent TB defined in Section 4.3. of the protocol. 25. Have a contradiction to obtaining an MRI or are unable to tolerate MRI procedures. 26. Have received a BCG vaccination within 1 year prior to screening. 27. Have ever received natalizumab or other agents that target alpha-4-integrin. | |
E.5 End points |
E.5.1 | Primary end point(s) | The cumulative number of new Gd-enhancing T1-weighted lesions on cranial MRIs through week 23. | |
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description | The study will be conducted with 2 subject cohorts | |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 | The trial involves single site in the Member State concerned | No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |