Reduction of plasma cells as an approach to reset autoimmunity in rheumatoid arthritis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Charite Universitaetsmedizin Berlin KöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

11 Mar 2025 → ongoing

Decision date (initial)

2024-03-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-511536-27-00

EudraCT number

2021-006669-40

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

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.

Conditions and MedDRA coding

Rheumatoid arthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Fulfilment of the 2010 ACR-EULAR criteria of rheumatoid arthritis
2. ACPA positivity (above the laboratory reference level for positivity)
3. Disease activity score DAS28-ESR >3.2
4. 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)
5. 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
6. 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
7. Fulfilment of the requirements for the administration of abatacept as stated in the abatacept SmPC

Exclusion criteria 14

1. Planned or ongoing pregnancy or breast-feeding
2. Hypersensitivity to the IMP, severe and uncontrolled infections such as sepsis and opportunistic infections
3. Severe and uncontrolled infections such as sepsis and opportunistic infections
4. Hereditary fructose intolerance (HFI)
5. Vaccination with attenuated vaccines during the course of the study
6. Ongoing or previous treatment with daratumumab
7. Concomitant treatment with other bDMARDs and/or tsDMARDs
8. Concomitant treatment with high potency opioid analgesics (e.g. methadone, hydromorphone, morphine)
9. Concomitant treatment with high-dosed glucocorticoids (>30 mg prednisolone equivalent per day except for daratumumab premedication)
10. Active ongoing inflammatory diseases other than RA
11. Malignant disease or history of malignant disease within 5 years prior to screening
12. 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
13. History of known chronic obstructive pulmonary disease (COPD: severity I-IV, bronchial asthma: severity 2-4)
14. Prior primary non-response or intolerance to abatacept or treatment with abatacept within the last 6 months before baseline

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Incidence and grading of severity of Injection Related Reactions (IRR) and toxicity after administration of daratumumab until week 12
2. AE and SAE due to IMP (both, daratumumab and abatacept) throughout the whole study
3. Percentage of subjects with ACPA seroconversion (below the laboratory reference level for positivity)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Charite Universitaetsmedizin Berlin KöR

Sponsor organisation

Charite Universitaetsmedizin Berlin KöR

Address

Chariteplatz 1, Mitte Mitte

City

Berlin

Postcode

10117

Country

Germany

Scientific contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

PD Dr. med. David Simon

Public contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

PD Dr. med. David Simon

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications