|- candidate number||8270|
|- NTR Number||NTR2434|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||28-jul-2010|
|- Secondary IDs||2009-017306-36 EudraCT number|
|- Public Title||Trial of anti IgE in RA.|
|- Scientific Title||Anti-IgE therapy (omalizumab) in IgE-ACPA positive RA.|
|- hypothesis||Recent data showed for the first time that IgE-ACPA antibodies have a direct biological immune response in mast cells of IgE-ACPA+ RA patients. Subsequently, mast cell targeting agents, such as anti-IgE therapy have rationale for application in RA patients.|
|- Healt Condition(s) or Problem(s) studied||Rheumatoid arthritis|
|- Inclusion criteria||1. Patients with refractory active rheumatoid arthritis (RA). Refractory disease is defined as persistent or relapsed disease activity despite conventional treatment, i.e. combination of disease modifying antirheumatic drugs including maximal tolerable doses of methotrexate. Active disease is defined as a DAS44 (Disease Activity Score of 44 joints) score of more than 3.6;|
2. Presence of IgE-ACPA;
3. Age above 18 years;
4. WHO performance status 0, 1 or 2;
5. Informed consent according to rules and regulations of Leiden University Medical Center.
|- Exclusion criteria||1. History of allergic or anaphylactic reaction to any therapeutic agent or known hypersensitivity to any component of anti-IgE monoclonal antibodies or to murine proteins;|
2. No previous therapy with corticosteroids or a biological agent during the last 3 months;
3. No previous therapy with rituximab, leflunomide;
4. Life expectation of less than 6 months;
5. History of severe CNS disturbances and psychiatric problems;
6. Severe uncontrolled infections including parasitosis;
7. Irreversible major organ dysfunction, defined by any of the following criteria:
A. Creatinine clearance < 40 ml/min;
B. Left ventricular ejection fraction < 40%;
C. Pericardial effusion with haemodynamic consequences;
D. Resting arterial oxygen tension (PaO2) < 8 kPa (<60 mmHg) and / or resting arterial carbon dioxide tension (PaCO2) > 6.7 kPa (>50 mmHg);
E. Sustained 3-fold increase in serum transaminase or bilirubin.
8. HIV positivity;
9. Positive pregnancy test or unwillingness to use adequate contraception for the duration of the study;
10. History of cancer, including solid tumors, hematological malignancies and carcinoma in situ (except for basal cell and squamous cell carcinoma of the skin that have been treated and cured).
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-jan-2011|
|- planned closingdate||30-jun-2012|
|- Target number of participants||80|
|- Interventions||This investigation is a placebo-controlled randomized double blinded single-center phase IIa study, administering subcutaneously every four weeks 300 mg of monoclonal anti-IgE antibody or placebo in patients with IgE-ACPA positive RA during 6 months.|
|- Primary outcome||1. Clinical parameters for disease activity are measured by the DAS44 (Disease Activity Score on 44 joints) assessment. Responses are classified as follows:|
A. Complete response is defined as a DAS44 improvement of > 1.2 and DAS<2.4;
B. Moderate response is defined as DAS44 improvement of 1.2 and DAS >2.4 or DAS 44 improvement of >0.6 en <=1.2 and DAS <=3.7;
C. Non-response is defined as DAS44 improvement of >0.6 en <=1.2 improvement and DAS >3.7 or improvement of <=0.6.
2. Immunological parameters in peripheral blood and synovium after treatment with anti-IgE antibodies (omalizumab) are:
A. Proportion of peripheral blood basophils, mast cells in synovium;
B. Functional presence of IgE-ACPA;
C. IgE , FcERI expression on basophils, mast cells, B cells and DC;
D. Synovial infiltration of B cells, plasmacells, mast cells and (IgE-)ACPA presence in synovial fluid.
3. Safety and toxicity parameters are evaluated according to WHO Common Toxicity Criteria.
|- Secondary outcome||N/A|
1. Day 0 = M0 baseline-visit 1;
2. Day 28 = M1 visit 2;
3. Day 56 = M2 visit 3;
4. Day 84 = M3 visit 4;
5. Day 112 = M4 visit 5;
6. day 140 = M5 visit 6;
7. Day 168 = M6 visit 7.
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES|| A.J.M. Schuerwegh|
|- CONTACT for SCIENTIFIC QUERIES|| A.J.M. Schuerwegh|
|- Sponsor/Initiator ||Leiden University Medical Center (LUMC)|
(Source(s) of Monetary or Material Support)
|Leiden University Medical Center (LUMC)|
|- Publications||Schuerwegh AJM, Ioan A, Dorjée AL, Roos J, Bajema IM, van de Voort EIH, Huizinga TWJ, Toes REM. Evidence for a functional role of IgE anticitrullinated protein antibodies in rheumatoid arthritis. Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2586-91.
Schuerwegh AJM, Ioan A, Dorjée AL, van de Voort EIH, Huizinga TWJ, Toes REM. The Functional Role of IgE-Anti Citrullinated Peptide/Protein Antibodies in Rheumatoid Arthritis. Ann Rheum Dis 2009;68(suppl I):A18-A19. Oral presentation on European Workshop of Rheumatology Research (EWRR) February 26-28th, 2009, Warsaw, Poland.
Direct activation of IgE-ACPA positive cells in rheumatoid arthritis. Schuerwegh AJM, Ioan A, Dorjée AL, van de Voort EIH, Huizinga TWJ, Toes REM. Ann Rheum Dis 2009;68(supplIII):150. Oral presentation on European League of Arthritis and Rheumatism (EULAR) June 10t -13th, 2009, Copenhagen, Danmark.
Citrullinated Proteins Activate IgE-ACPA+ Cells in Rheumatoid Arthritis. Annemie JM Schuerwegh, Andreea Ioan-Facsinay, Annemarie L. Dorjée, Ellen IH van der Voort, Tom WJ Huizinga and René EM Toes. Annual Congres on Rheumatology ACR/AHRP Scientific Meeting October 2009, Philadelphia, USA. |
|- Brief summary||This investigation is a double blinded single-center placebo controlled randomized phase IIa study, administering subcutaneously monoclonal anti-IgE antibody (300mg/month) or placebo in IgE-ACPA positive RA patients, refractory to methotrexate. This study evaluates the safety and efficacy of anti-IgE therapy with respect to: Clinical (DAS), laboratory parameters and adverse events. In addition, this study investigates whether disease activity correlates with immunological parameters, including immunopathology and IgE-ACPA-autoantibodies. |
|- Main changes (audit trail)|
|- RECORD||28-jul-2010 - 11-apr-2011|