|- candidate number||6703|
|- NTR Number||NTR2098|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||9-nov-2009|
|- 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 active rheumatoid arthritis (RA). These include patients with risk of permanent disability, irreversible major organ failure or premature mortality. 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 2.4; |
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 a biological agent or known hypersensitivity to any component of anti-IgE monoclonal antibodies or to murine proteins;|
2. Life expectation of less than 6 months;
3. History of severe CNS disturbances and psychiatric problems;
4. Severe uncontrolled infections including parasitosis;
5. 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.
6. HIV positivity.
|- mec approval received||no|
|- multicenter trial||no|
|- Type||Single arm|
|- planned startdate ||1-jan-2010|
|- planned closingdate||31-dec-2012|
|- Target number of participants||10|
|- Interventions||A prospective open single-center, phase IIa study investigating anti-IgE therapy (Omalizumab) in refractory IgE-ACPA+ RA patients. |
We are administering subcutaneously monoclonal anti-IgE antibody (0.016mg/kg/IU IgE/mL, depending on the total serum IgE/2-4weeks) in IgE-ACPA positive RA patients, refractory to methotrexate.
|- 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 < 1,6;
B. Clinical complete response is defined as a DAS44 < 2,4 or fulfillment of EULAR criteria for „good improvement“;
C. Clinical partial response is defined when EULAR criteria for „moderate improvement“ is fulfilled;
D. Progressive disease is defined as DAS44 increasing or decreasing less than 10% from baseline;
E. Non-response is defined as DAS44 increasing more than 10% of baseline after 1 month of treatment.
2. Immunological parameters in peripheral blood and synovium after treatment with anti-IgE antibodies (Omalizumab) are:
A. Proportion of basophils, mast cells;
B. Functional presence of IgE-ACPA;
C. Production of auto-antibodies (ACPA isotypes);
D. Synovial infiltration of 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. D0 = M0 baseline-visit 1;
2. D28 = M1 visit 2;
3. D56 = M3 visit 3;
4. D84 = M4 visit 4;
5. M6 visit 5.
|- 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, 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 open label single-center phase IIa study, administering subcutaneously monoclonal anti-IgE antibody (0.016mg/kg/IU IgE/mL, depending on the total serum IgE/2-4weeks) 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||9-nov-2009 - 21-nov-2009|