E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rheumatoid arthritis |
Rheumatoide Arthritis |
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E.1.1.1 | Medical condition in easily understood language |
Rheumatoid arthritis |
Rheuma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• 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
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• Untersuchung der Sicherheit einer kombinierten Behandlung mit Abatacept und Daratumumab bei Patienten mit ACPA-positiver Rheumatoider Arthritis • Untersuchung der klinischen Wirksamkeit einer kombinierten Behandlung mit Abatacept und Daratumumab bei Patienten mit ACPA-positiver Rheumatoider Arthritis
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E.2.2 | Secondary objectives of the trial |
• To achieve drug-free clinical remission after combined abatacept/daratumumab treatment. |
Erreichen einer therapiefreien Remission nach kombinierter Behandlung mit Abatacept/Daratumumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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
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E.5 End points |
E.5.1 | 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.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
week 48 vs week 24; week 48 vs week 0 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
new indication, new combination |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |