relapsing-remitting Multiple Sclerosis MedDRA version: 9.1 Level: LLT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis
Conditions
Interventions
Product Name: ETIMS (EDC-fixed autologous PBMCs coupled with 7 immunodominant myelin peptides in MS patients)
Product Code: ETIMS
Pharmaceutical Form: Intravenous infusion
Sponsors
University Medical Center Hamburg-Eppendorf
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria for dose escalation period of the study Six patients will be included in the dose escalation study. To be eligible for entry into the dose escalation study, patients must meet the following criteria at the time of enrolment. a)Between the ages of 18 and 55 years. b)Patients with relapsing-remitting or secondary progressive MS according to published criteria (51) c)EDSS score between 1 and 5.5. d)Patients are off-treatment for standard therapies (interferon-beta, glatiramer acetate, natalizumab, mitoxantrone) e)Patients are able to provide written, informed consent prior to any testing under this protocol, including screening and baseline investigations that are not considered part of routine patient care. Patient decision not to start, or not to continue with standard immunomodulatory therapy, has to be made by the patient after discussing conventional treatment options with a neurologist not directly involved in the study to ensure the patient has made an informed decision. Additionally, the informed consent form provided to the patient will explicitly state the currently approved therapies and their potential benefits. See page 38 for a discussion of the ethical requirements in regards to conventional treatment options. Inclusion criteria for pre-treatment screening for the established dose period of the study To be eligible for entry into the study, patients must meet the following criteria at the time of enrolment. Re-assessment of the inclusion criteria will occur on day zero of the twelve-month treatment phase. a)Between the ages of 18 and 55 years. b)Patients with relapsing-remitting MS according to published criteria c)EDSS score between 1 and 5.5. d)Disease duration = 5 years e)Patients have either failed standard therapies (interferon-beta, glatiramer acetate) by clinical measures, or are not eligible for standard therapies, or opted not to start or continue with any of the standard therapies. f)Patients are able to provide written, informed consent prior to any testing under this protocol, including screening and baseline investigations that are not considered part of routine patient care. Patient decision not to start, or not to continue with standard immunomodulatory therapy, has to be made by the patient after discussing conventional treatment options with a neurologist not directly involved in the study to ensure the patient has made an informed decision. Additionally, the informed consent form provided to the patient will explicitly state the currently approved therapies and their potential benefits. See page 38 for a discussion of the ethical requirements in regards to conventional treatment options. 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
Exclusion criteria: Patients will be excluded from the study if any of the exclusion criteria exist at the time of enrolment. Re-assessment of the exclusion criteria will occur on day zero of the six month treatment follow-up phase. Medical history a)Diagnosis of secondary-progressive or primary-progressive MS, as defined by published diagnostic criteria (51). b)Abnormal screening/baseline blood tests exceeding any of the limits defined below: ?Serum alanine transaminase or aspartate transaminase levels which are greater than three times the upper limit of normal values. ?Total white blood cell count 2.0 mg/dl, if serum creatinine level > 1.2 mg/dl, glomerular filtration rate must be determined, patients are excluded if it is <30mL/minute ?Positive pregnancy test c)Pregnant or breast-feeding female. d)History or signs of immunodeficiency. e)Concurrent clinically significant (as determined by the investigators) cardiac, immunological, pulmonary, neurological, renal or other major disease. f)Splenectomy g)History of HIV or positive HIV antibody testing h)Positive for hepatitis C antibody and/or positive for Hepatitis B surface antigen at screening. i)Patients with cognitive impairments who are unable to provide written, informed consent prior to any testing under this protocol, including screening and baseline investigations that are not considered part of routine patient care. Treatment history a)If prior treatments were administered, the patient must be off treatment for the required period prior to enrolment. Time required off agent prior to enrolment 24 weeks: Alemtuzumab, Rituximab, Methotrexate, Cyclophosphamide, Cyclosporine, T cell or TCR vaccination, DNA plasmid vaccination, Cladribine, any monoclonal antibody and any other immunosuppressive treatments 12 weeks: Glatiramer Acetate, Interferon-beta, Natalizumab, Azathioprine, Mitoxantrone, IVIg, Plasma Exchange 4 weeks: Corticosteroids b)Prior treatment with other investigational drugs or procedures will be evaluated individually by the investigators. Miscellaneous a)History of alcohol or drug abuse within the 5 years prior to enrolment. b)Female patients who are not post-menopausal or surgically sterile who are not using an acceptable method of contraception. Acceptability of various methods of contraception will be at the discretion of the investigator. Documentation that the patient is post-menopausal or surgically sterile must be available prior to enrolment. c)Male patients who are not surgically sterile and not practicing adequate contraception. Acceptability of various methods of contraception will be at the discretion of the investigator and will be discussed in details with all male patients during the informed consent procedure. Documentation that the patient is surgically sterile must be available prior to enrolment. d)Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that is likely to affect the patient returning for follow-up visits on schedule. e)Previous participation in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: 1) To investigate the effect of i.v. administered peptide- pulsed PBMC on secondary and tertiary outcome parameters, consisting of clinical and MRI measures. 2) To investigate the mechanisms of action of peptide-pulsed EDC-fixed PBMC on inflammatory activity in MS.;Main Objective: To investigate the safety and tolerability of antigen-specific tolerization with peptide-pulsed PBMC in RR-MS and to examine the efficacy of tolerization with peptide-pulsed PBMC in reducing the inflammatory activity in the central nervous system;Primary end point(s): Evaluation of safety The safety population is defined as all patients who received peptide-coupled PBMC and have at least one clinical assessment and/or one cranial MRI. If a cranial MRI is not available the clinical assessment will be included in the safety analysis. In case that no clinical assessment is available all clinical information retrievable by direct telephone visit or medical reports from other MDs/hospitals will be included in the safety analysis. The incidence of all adverse events reported by the investigator and/or the patient will be tabulated by severity and relationship to treatment. Laboratory evaluations will be assessed to determine incidence of clinically notable abnormalities that emerge during the course of the study. MRI safety measures include the comparison of CELs and other MRI measures between baseline and treatment phase. Clinical safety measures are the changes in SNRS, EDSS, MSFC, UNDS from baseline to treatment phase. The annualized relapse rate before treatment will be compared to the treatment phase. The long term safety of ETIMS will be assessed in a follow-up visit at month 12 and evaluated separately. Evaluation of Efficacy The efficacy of intravenously administered peptide-coupled PBMCs in patients with MS will be evaluated by comparing the mean number of CELs present on cranial MRI during the pre-treatment baseline phase to the treatment phase. The primary ef | — |
Countries
Germany
Outcome results
None listed