Rheumatoid arthritis MedDRA version: 23.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Trade Name: Orencia Injektionslösung in einer Fertigspritze
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ABATACEPT
CAS Number: 332348-12-6
Concentration unit:
Sponsors
Universitätsklinikum Erlangen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Fulfilment of the 2010 ACR-EULAR criteria of rheumatoid arthritis • CCP antibody positivity (cut off 5 RE/ ml) • Disease activity score DAS28-ESR > 3.2 • Inadequate treatment response and/ or intolerance to at least one csDMARD (e.g. MTX) and/or bDMARDs (e.g. TNF-alpha inhibitors or IL-6 blockers or tsDMARDs) • csDMARD: only simultaneous therapy with MTX (if tolerated) allowed, i.e. Sulfasalazin, Hydroxychloroquine and Leflunomide must be stopped during screening phase and be replaced by MTX • Women of childbearing potential (WOCBP) must use adequate effective methods of contraception during participation in the study and 3 months after the last dose of Daratumumab or 14 weeks after the last dose of Abatacept • Fulfilment of the requirements for the administration of abatacept as stated in the abatacept SmPC 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 17 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: • Planned or ongoing pregnancy or breast-feeding • Ongoing or previous treatment with abatacept or daratumumab • Concomitant treatment with other bDMARDs and/ or tsDMARDs • Concomitant treatment with high potency opioid analgesics (e.g. methadone, hydromorphone, morphine) • Concomitant treatment with high-dosed glucocorticoids (> 30 mg prednisolone equivalent per day except for daratumumab premedication) • Active ongoing inflammatory diseases other than RA • Malignant disease or history of malignant disease within 5 years prior to screening • Chronic infection such as latent TB (not adequately treated according to guidelines), HIV infection or active hepatitis B, C or history of hepatitis B, C • History of known chronic obstructive pulmonary disease (COPD: severity I-IV, bronchial asthma: severity 2-4)) • Hypersensitivity to the IMP, severe and uncontrolled infections such as sepsis and opportunistic infections. • Severe and uncontrolled infections such as sepsis and opportunistic infections • hereditary fructose intolerance (HFI) • Vaccination with attenuated vaccines during the course of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To assess the safety of combined abatacept/daratumumab treatment in ACPA-positive RA subjects •To assess the clinical efficacy of combined abatacept/daratumumab treatment in ACPA-positive RA subjects ;Secondary Objective: •To achieve drug-free clinical remission after combined abatacept/daratumumab treatment.;Primary end point(s): Safety (Phase I + II): •Incidence and grading of severity of Injection Related Reactions (IRR) and toxicity after administration of daratumumab until week 12. •AE and SAE due to IMP (both, daratumumab and abatacept) throughout the whole study. Clinical efficacy (Phase II): •Percentage of subjects with anti-CCP2 antibody seroconversion = CCP2 antibody level <5 RE/ml at week 24. ;Timepoint(s) of evaluation of this end point: week 12/24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Serological: • Change in anti CCP2 antibody levels (RE/ml) • Change in anti CCP2 antibody levels (RE/ml) in HLA-defined subgroups • Change in total IgG, IgA, IgM subclasses • Change in glycosylation profile of total IgG and CCP2 antibodies • Change in the number of plasmablasts, B cell and T cell numbers • Change in numbers of CCP2-specific plasmablasts and B-cells • Change in number of CD38+ T cells Clinical: • TJC/SJC • DAS28-CRP • SDAI / CDAI • Percentage of patients in clinical remission (DAS28-ESR<2.6) • ACR 20, 50, 70 response rates ;Timepoint(s) of evaluation of this end point: week 48 vs week 24; week 48 vs week 0 | — |
Countries
Germany
Contacts
Public ContactMedizinische Klinik 3
Universitätsklinikum Erlangen
Outcome results
None listed