This trial will test the efficacy of Kepivance in the prevention of new autoimmune diseases in patients who have multiple sclerosis (MS)who are being treated with alemtuzumab. MedDRA version: 14.1 Level: PT Classification code 10058948 Term: Nephritis autoimmune System Organ Class: 10038359 - Renal and urinary disorders MedDRA version: 14.1 Level: PT Classification c
Conditions
Interventions
Trade Name: Kepivance
Product Name: Kepivance
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Palifermin
CAS
Sponsors
Cambridge University Hospitals NHS Foundation Trust and University of Cambridge
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be included in the trial the patient must have/be: • Male or non-pregnant, non-lactating female patients • Aged between 18 and 50 years inclusive • Diagnosis of MS using McDonald’s criteria, including diagnostic MRI • Onset of first MS symptoms within 10 years • EDSS score 0.0 to 5.0 (inclusive) at screening • At least 2 clinical episodes of MS in the 2 years prior to study entry, with at least 1 attack within 12 months, which may have occurred whilst on disease-modifying therapy, such as beta interferon therapy or glatiramer acetate. • Serum IL-21 =230pg/mL. Apart from the IL-21 inclusion criterion, the details of patient selection are identical to those adopted in the phase 3 trials of alemtuzumab (CARE MS1 and MS2). This ensures that the results of this trial can be generalised to these patient groups. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 86 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: The presence of any of the following will preclude patient inclusion: •Any progressive form of multiple sclerosis •Previous thymectomy •Previous treatment with alemtuzumab, mitoxantrone, cyclophosphomide, cladribine, rituximab or any other immunosuppressant or cytotoxic therapy (other than steroids) •History of malignancy •Personal history of clinically significant autoimmune disease, other than multiple sclerosis (including but not limited to: thyroid disease, immune cytopenias, inflammatory bowel disease, diabetes, lupus, severe asthma) •Intolerance of pulsed corticosteroids, especially a history of steroid psychosis •Major systemic disease or other illness that would, in the opinion of the investigator, compromise patient safety or interfere with the interpretation of study results. •Seropositivity for human immunodeficiency virus (HIV) •Past or present hepatitis B infection (positive hepatitis B serology) •Pregnant women or male and female patients who do not agree to use effective contraception during the study. Reliable and effective contraceptive method(s) include: intrauterine device (IUD), hormonal based contraception, surgical sterilisation, abstinence, or double barrier contraception i.e. condom and occlusive cap (diaphragm or cervical cap with spermicide). • Medical, psychiatric, cognitive or other conditions that, in the investigator's opinion, compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to determine if Kepivance can prevent patients with multiple sclerosis from developing new autoimmune diseases after treatment with alemtuzumab.;Secondary Objective: Our secondary objective is to determine if Kepivance can boost the function of the thymus in adult humans. The thymus is a gland that sits in the neck. Its function is to make new immune cells. If Kepivance can boost the function of the thymus gland this has important implications for a number of patient groups - for example patients who have reduced numbers of immune cells due to HIV infection, or because of treatment with chemotherapy drugs.;Primary end point(s): The primary endpoint is incidence of clinical autoimmunity within 30 months of starting treatment with alemtuzumab.;Timepoint(s) of evaluation of this end point: Patients will be assessed for development of autoimmunity at all routine study visits - Months 1,3 6,9,12,13, 15,18,21,24,27,30. In addition patients will have monthly full blood counts to screen for the development of immune thrombocytopenia. The primary endpoint will be assessed once all patients have completed 30 months on study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Percentage of naive T cells • Safety outcomes - incidence and nature of adverse events • Percentage of central memory T cells, effector memory T cells and T effector memory RA cells - as determined by flow cytometry • Frequency of recent thymic emigrants (defined by co-expression of CD45RA and CD31 in CD4+ T cells, and by CD45RA and CD103 in CD8+ T cells) - as determined by flow cytometry • T cell receptor (TCR) clonality - as determined by CDR3 spectratyping • Thymic function - as determined by measuring TRECs • Thymic volume and density - as assessed by non-contrast helical CT scans of the thymus performed at baseline, then again at 6 months following treatment. The scans will be analysed by a blinded thoracic radiologist who will perform a quantitative computer based analysis in order calculate thymic volume and density.;Timepoint(s) of evaluation of this end point: Safety assessment and recording of all adverse events will be performed throughout the study, and reviewed at all study visits- Months 1,3 6,9,12,13, 15,18,21,24,27, and 30. CT scans of the chest, to measure thymic volume and density, will be performed at baseline and month 6. Immunological assays of thymic function will be performed at baseline and again at months 1,3 6,9,12,13, 15,18,21,24,27, and 30. | — |
Countries
United Kingdom
Contacts
Public ContactMrs Carrie Bayliss
Cambridge University Hospitals NHS Foundation Trust
Outcome results
None listed