Rheumatoid Arthritis MedDRA version: 14.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Trade Name: Alemtuzumab (already received by alemtuzumab cohort between 1991 and 1994
manufacturerd by Cambridge Therapeutic Antibody Centre, Burroughs Wellcome, Glaxo Wellcome)
Product Name: Alemtuzumab (already received by alemtuzumab cohort between 1991 and 1994)
Pharmaceutical Form
Sponsors
The Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All study participants must be able and willing to provide informed consent prior to any study-specific procedures, including immunisation. NOTE: Alemtuzumab recipients who do not wish to take part in the study (i.e. attend Addenbrooke’s for study procedures as outlined in Protocol Section 13.1, including blood samples with/without vaccination), but who are happy for morbidity information only to be collected via a phone call or via GP records on one occasion only (as per screening/baseline visit) will indicate their intention in writing on the study “Expression of Interest” form. Alemtuzumab recipients (cases) • Received alemtuzumab in original Cambridge studies (1991-94) Matched controls • Rheumatoid arthritis according to 1987 ACR criteria • Disease duration within 5 years of matched case • Age within 10 years of matched case • Gender profile to match alemtuzumab recipients 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 16 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: Both groups • Contra-indications to vaccination (as per SmPCs – see protocol Appendices B-D) • Recent vaccination with study strain of flu vaccine • Vaccination with tetanus, diphtheria, polio or pneumococcus within past 5 years (contra-indication to the specific vaccine only) Controls only • Received rituximab within past 3 months • Treatment with any investigational agent within 12 weeks or 5 half-lives of the investigational drug NOTE: Eligible patients (control or alemtuzumab cohort) who have received vaccination with pneumococcus, tetanus, diphtheria, or polio within the past 5 years will not be excluded from the study, but will NOT be revaccinated with the specific vaccine as relevant, i.e. Revaxis and/or Pneumovax II. NOTE: Eligible patients (control or alemtuzumab cohort) who are also women of child-bearing potential will have pregnancy status checked by a serum pregnancy test at the screening visit. Women who are subsequently confirmed as pregnant or who are breast feeding will NOT be excluded from the study but will NOT receive any of the three vaccines at the screening/baseline visit. Results from the serum pregnancy test (where relevant) must be obtained prior to vaccination. For relevant female patients whose pregnancy test is negative, a separate baseline visit is needed for vaccination only (once pregnancy results are known). The separate baseline visit must be within 7 days of the screening visit; the date of vaccination (baseline) would then be Day 0.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the ability to mount immune responses (to measure the function of the immune system) in patients who received alemtuzumab for rheumatoid arthritis between 1991 and 1994 and a matched control group with long-standing rheumatoid arthritis. The control group will be matched for disease duration (within 5 years of matched case), age (within 10 years of matched case) and gender.;Secondary Objective: To update data regarding reconstitution of lymphocytes (white blood cell believed to contribute to Rheumatoid Arthritis), mortality and morbidity in the group of patients who received alemtuzumab between 1991 and 1994. To compare specific parameters of immune function in alemtuzumab patients and controls (lymphocyte subsets by flow cytometry; Circulating cytokine levels; Thymic function; Serum immunoglobulins and serum protein electrophoresis; Rheumatoid factor and anti-CCP levels). To collect information on current disease activity in alemtuzumab patients and controls (Swollen joint count; Tender joint count; Patient VAS; ESR/CRP).;Primary end point(s): The primary outcome variable is serological response 4 weeks after immunisation.;Timepoint(s) of evaluation of this end point: Day 28 (+/- 48 hours) after immunisation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): In alemtuzumab cohort only: • Mortality data to be obtained via the Office for National Statistics. Death certificates will be requested for those patients who have died since last follow-up to confirm cause of death. The alemtuzumab cohort are already flagged via Office for National Statistics for flagging and tracing (with consent). • Morbidity data collected will relate specifically to infectious and malignant morbidity since last follow-up. In both patient groups: • Adverse event profile at 4 weeks after immunisation. • Full blood count and lymphocyte subsets • Serum protein electrophoresis and immunoglobulin levels • T-cell receptor excision circles (measurement of thymic activity) • Serum cytokines (at minimum IL7, IL15, IL21) • Autoantibody levels • Disease activity score using 28 joints (DAS28) – Swollen joint count, Tender joint count, Patient VAS, ESR, CRP (Protocol Appendix E). • ACR Core Criteria, including Patient Health Assessment Questionnaire and Patient pain VAS (Protocol Appendix F);Timepoint(s) of evaluation of this end point: In alemtuzumab cohort only: • Mortality data - as and when received by ONS. • Morbidity data - collected at combined screening/baseline visit only(or on one occassion only, via phone call to patient or via GP records, if pt does not wish to take part in study but happy for morbidity information to be collected only) In both patient groups: • Adverse event profile - 4 weeks after immunisation (Day 28 +/- 48 hours). • Full blood count and lymphocyte subsets, Serum protein electrophoresis and immunoglobulin levels, T-cell receptor excision circles (measurement of thymic activity), Serum cytokines (at minimum IL7, IL15, IL21), Autoantibody levels, Disease activity score using 28 joints (DAS28), ACR Core Criteria - at combined screening/baseline visit only. | — |
Countries
United Kingdom
Outcome results
None listed