Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis MedDRA version: 8.1 Level: LLT Classification code 10050894 Term: Anti-neutrophil cytoplasmic antibody positive vasculitis
Conditions
Interventions
Product Name: Abatacept
Product Code: BMS-188667
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Abatacept
CA
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with Acute AAV, presenting at first diagnosis or relapse (not grumblers, to maximize effect seen), defined by clinical presentation, ANCA positivity (anti-MPO or anti-PR3 positive) and a BVAS score of > 8. 2. Males and females (not nursing and not pregnant) at least 18 years of age. Women of child bearing potential are eligible if they are practicing effective contraceptive measures 3. Written informed consent given 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) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects with severe life-threatening disease, i.e. lung haemorrhage at the time of presentation, renal impairment with SCr>150 mcmol/l, or severe CNS dysfunction thought to be due to vasculitis 2. Subjects with current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral disease, or other medical conditions that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study. 3. Subjects with any other non-vasculitic multisystem autoimmune disease. 4. Subjects with any serious acute bacterial infection unless treated and completely resolved with antibiotics prior to enrollment 5. Subjects with any severe chronic or recurrent bacterial infection, e g. bronchiectasis, osteomyelitis, chronic pyelonephritis 6. Subjects with Hepatitis B or C or HIV. 7. Subjects with Herpes zoster infection that resolved less than 2 months prior to enrollment. 8. Subjects who have received any live vaccines within 3 months of the first dose of study medication or who will have need of a live vaccine at any time in the year following enrollment 9. Subjects with current clinical or laboratory evidence of active or latent tuberculosis (TB) and subjects with a history of active TB treated within the last 3 years should be excluded. Subjects who received treatment for active TB greater than 3 years ago may be eligible for inclusion in this study if there is documentation of the prior anti-TB treatment confirming that it was appropriate in duration and type. 10. Subjects with any previous malignancy, with the exception of non-melanoma skin malignancies, adequately treated previously 11. Subjects with a mammogram that is suspicious for malignancy and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations. Mammograms (females only) must be performed within 6 months of study entry or if documentation is not on file 12. Pregnancy or breast feeding. Adequate contraception is necessary; 13. Subjects with MTX treatment in prior 3 months 14. Subjects with allergies to study medications. 15. Prior therapy with rituximab within the last 6 months (CD19 count must be normal before enrollment regardless of time of last dose). ; anti-TNF therapy, or IL-1 receptor antagonists within the last 3 months. 16. Subjects participating concurrently in another clinical trial. 17. Subjects with a history of intolerance to methotrexate. 18. Subjects who have at any time received treatment with abatacept. 19. Subjects who have received treatment with any investigational drug within 28 days (or less than 5 terminal half-lives of elimination) of the Day 1 dose. 20. Subjects with any of the following laboratory values: - Hgb 2 times upper limit of normal. -Any ot
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the relapse rate (defined by clinical and biochemical parameters) over 24 months in patients with acute AAV presenting at first diagnosis of relapse, after 12 months of treatment with abatacept in combination with steroids and methotrexate or placebo in combination with steroids and methotrexate. ; Secondary Objective: To assess the clinical efficacy of abatacept combined with MTX + steroids vs placebo and MTX + steroids by measuring: 1. The sustained remission rate 2. Time to remission 3. The average steroid dosage at 6, 12, 18 and 24 months in abatacept and placebo groups respectively 4. Time to ANCA negativity by immunofluorescence or negative anti-PR3 or anti-MPO Ab test by ELISA. 5. Proportion of patients defaulting to cyclophosphamide therapy. 6. Proportion of patients unable to stick with trial protocol. 7. Degree of chronic disease activity 8. Health related quality of life To assess the safety and tolerability of abatacept in this study population, evaluated by number of adverse events ; Primary end point(s): Response to treatment measured by: Relapse rates in patients who have achieved remission over 24 month study period. Proportion of patients in sustained remission at 6, 12, 18 and 24 months; time to remission; The average steroid dosage at 6, 12,18 and 24 months; Time to ANCA negativity by immunofluorescence or negative anti-PR3 or anti-MPO Ab test by ELISA; Urinary MCP-1 measurement to assess disease activity in those with kidney disease. In both groups, disease will be monitored using the well established and validated BVAS 2003, in conjunction with biochemical, immunological, radiological and other physiological parameters, which we regularly use to assess disease activity. The definitions of remission ( | — |
Countries
Germany, Netherlands, United Kingdom
Outcome results
None listed