Relapsing Remitting Multiple Sclerosis MedDRA version: 14.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: TYSABRI
Product Code: AN100226, BG00002
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: NATALIZUMAB
CAS Number: 189261-10-7
Concentration unit: mg milligram
Sponsors
Biogen Idec Research Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of enrollment or at the timepoint specified in the individual eligibility criterion listed: 1. Ability of parents or legal guardians to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations. Subjects may provide assent in addition to the parental or guardian consent, if appropriate. 2. Aged from 10 to less than 18 years old at the time of informed consent or assent. 3. Diagnosis of RRMS according to Krupp [Krupp 2007] on behalf of the International Pediatric MS Study Group and Polman [Polman 2011] at Screening. RRMS diagnosis must be confirmed by a brain MRI scan performed within the 12 months prior to Screening or at Screening. 4. It has been determined by the treating physician that natalizumab treatment is appropriate for this subject based on their disease status. 5. Subjects of childbearing potential, who are sexually active, must practice effective contraception during the study and be willing and able to continue contraception for 3 months after their last infusion of study treatment. For further details of contraceptive requirements for this study, please refer to Section 15.5.3. Are the trial subjects under 18? yes Number of subjects for this age range: 12 F.1.2 Adults (18-64 years) no 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
Exclusion criteria: Candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of enrollment or at the timepoint specified in the individual criterion listed: Medical History 1. Diagnosis of acute disseminated encephalomyelitis, neuromyelitis optica, isolated optic neuritis or transverse myelitis, progressive MS, or any other potential differential diagnosis of pediatric-onset RRMS. 2. History of human immunodeficiency virus. 3. History of hepatitis C virus antibody or current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]). Subjects with immunity to hepatitis B from previous natural infection (defined asnegative HBsAg, positive hepatitis B surface antibody immunoglobulin G, and positive HBcAb) are eligible to participate in the study (US Centers for Disease Control and Prevention’s interpretation of the hepatitis B serology panel). 4. History of or current signs and symptoms suggestive of PML. 5. History of inflammatory disorders, metabolic neurogenetic leukodystrophies, toxic leukoencephalopathies, or vascular conditions. 6. History of premalignant or malignant disease. 7. History of severe allergic or anaphylactic reactions, or known drug hypersensitivity. 8. Clinically significant infections or medical illness from 30 days prior to Screening or between Screening and the first infusion of study treatment. 9. Diagnosis of MS relapse within 30 days prior to enrollment. 10. History of, or abnormal laboratory values indicative of, significant medical, neurologic (other than MS), or psychiatric disorders that might preclude participation in the study in the opinion of the Investigator. 11. Abnormal laboratory values at Screening defined at following thresholds: a. bilirubin level >2 times the upper limit of normal (× ULN) b. absolute lymphocyte count =750/mm3, hemoglobin =10 g/dL, or platelet count =100,000/mm3 c. serum creatinine >1.5 mg/dL d. alanine aminotransferase (ALT), OR aspartate aminotransferase (AST), OR gamma-glutamyltransferase (GGT) >2 × ULN MS Treatment History 12. Prior natalizumab therapy. 13. Prior treatment with total lymphoid irradiation. 14. Prior treatment with cladribine, mitoxantrone, fingolimod, teriflunomide, T cell or T-cell receptor vaccination, cyclophosphamide, cyclosporine, azathioprine, methotrexate, mycophenolate mofetil, or any therapeutic monoclonal antibody or other immunosuppressive therapy. 15. Plasmapheresis or cytapheresis within 12 months prior to the first infusion of study treatment. 16. Prior treatment with intravenous immunoglobulin (IVIg) within 4 months prior to the first infusion of study treatment. 17. Treatment with IV or oral corticosteroids (topical corticosteroids are acceptable) or related products within 30 days prior to the first infusion of study treatment. 18. Immunomodulatory treatment, i.e., interferon beta or glatiramer acetate within 2 weeks prior to the first infusion of study treatment. Miscellaneous 19. Nursing or pregnant female, or female planning to become pregnant during study participation. 20. Participation in any other investigational study that involved treatment with an investigational drug or prior treatment with any experimental agent outside a clinical study. 21. Other unspecified reasons that, in the opinion of the Investigator and/or Biogen Idec, make the subject unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to determine the PK profile of multiple doses of natalizumab in pediatric subjects with RRMS.;Secondary Objective: The secondary objectives of this study in this study population are as follows: • To characterize the PD profile of natalizumab (as defined by a4 integrin binding). • To determine the safety and tolerability of multiple doses of natalizumab. ;Primary end point(s): The primary endpoints are as follows: maximum plasma concentration (Cmax) for the 24-hour sampling period, predose (trough) concentrations (Cpredose) from multiple dosing time to maximum plasma concentration (Tmax) for the 24-hour sampling period area under the plasma concentration curve from time of first dose to infinity (AUCinf), apparent clearance (Cl/F), volume of distribution, elimination half-life (t1/2) ;Timepoint(s) of evaluation of this end point: The primary endpoints are as follows: maximum plasma concentration (Cmax) for the 24-hour sampling period, predose (trough) concentrations (Cpredose) from multiple dosing time to maximum plasma concentration (Tmax) for the 24-hour sampling period area under the plasma concentration curve from time of first dose to infinity (AUCinf), apparent clearance (Cl/F), volume of distribution, elimination half-life (t1/2) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are as follows: the average and minimum saturation values of a4 integrin over the dosing interval, incidence of serious adverse events (SAEs), infusion and hypersensitivity reactions, and other AEs, the presence of anti-natalizumab antibodies;Timepoint(s) of evaluation of this end point: The secondary endpoints are as follows: the average and minimum saturation values of a4 integrin over the dosing interval, incidence of serious adverse events (SAEs), infusion and hypersensitivity reactions, and other AEs, the presence of anti-natalizumab antibodies | — |
Countries
Italy
Outcome results
None listed