Combination of baricitinib and anti-TNF in rheumatoid arthritis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Bordeaux

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

5 Feb 2025 → ongoing

Decision date (initial)

2024-05-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Biogen · Eli Lilly and Company · Ministry for Health and Solidarity, France

External identifiers

EU CT number

2024-511442-39-00

EudraCT number

2020-004345-37

ClinicalTrials.gov

NCT04870203

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To assess the clinical efficacy at 24 weeks of the combination strategy of anti-TNF therapy (adalimumab (40 mg every two weeks) or etanercept (50 mg every week)) with baricitinib (4mg daily) versus baricitinib alone (4mg daily) in patients with refractory RA.

Secondary objectives 11

1. Main secondary objectives : To assess the safety of the combination of baricitinib and anti-TNF therapy versus baricitinib alone, comparing the clinical and biological safety profiles through 24 weeks of follow-up
2. To assess drug retention rates at weeks 4, 12 and 24 in each treatment group
3. To assess the proportion of patients who decrease the glucocorticosteroid dose ≤ 5 mg per day, sustained from week 12 to week 24, among patients with a baseline dose > 5 mg per day, in each treatment group
4. To assess patient-reported outcomes (HAQ, FACIT, RAID) at week 24 in each treatment group
5. To assess the maintenance of clinical efficacy at week 52 in each treatment group
6. Main secondary objectives : To compare changes in DAS28-CRP score between baseline and week 24 in each treatment group.
7. Comparing the proportion of patients who have an ACR20 response and ACR70 response at weeks 4, 12 and 24 in each treatment group
8. Comparing the proportion of patients who have an ACR50 response at weeks 4 and 12 in each treatment group.
9. Comparing the proportion of patients who have a EULAR response at weeks 4, 12 and 24, according to DAS28-ESR in each treatment group.
10. Comparing the proportion of patients who present remission or low disease activity at weeks 4, 12 and 24, according to DAS28-ESR in each treatment group.
11. Comparing changes in DAS28-ESR, DAS28-CRP, sDAI and cDAI scores between baseline and each visit (until week 24, inclusive) in each treatment group.

Conditions and MedDRA coding

Rheumatoid arthritis (RA)

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age between 18 and 65 years-old
2. Adult patient with a diagnosis of RA as defined by the ACR/EULAR 2010 criteria for the classification of RA
3. Patient who presents an inadequate response to at least one bDMARD or tsDMARD for at least 12 weeks prior to study entry at a dose that is considered acceptable to assess clinical response adequately
4. Patient affected by active RA (DAS28-ESR > 3.2 or sDAI > 11 or cDAI > 10) eligible to receive a bDMARD or tsDMARD according to the French Society of Rheumatology guidelines
5. Patient treated by prednisone dosage ≤ 10mg per day. The corticosteroids dosage will be decreased to 7,5 mg/day at the beginning of the study (W0)
6. Person affiliated with or beneficiary of the French social security scheme
7. Free, informed and written consent signed by the participant and the investigator (on the day of inclusion at the latest and before any examination required by the research project)

Exclusion criteria 32

1. Patient previously treated with baricitinib
2. Patient previously treated by both adalimumab and etanercept. If the patient received previously only one of these two treatments, she/he can be included in the study but with the treatment she/he has not yet received (if she/he is randomized in the experimental COMBI group)
3. Patient affected by another form of inflammatory arthritis with the exception of secondary Sjögren syndrome
4. Patient who presents contraindications to the study treatments
5. Patient with a history of hypersensitivity to etanercept/baricitinib/adalimumab and any of the excipients
6. Patient who smokes or has done so for a long time in the past
7. Patient who is currently receiving corticosteroids at doses >10 mg of prednisone per day (or equivalent) or has been receiving an unstable dosing regimen of corticosteroids within 4 weeks of study entry
8. Patient who is currently receiving more than 1 concomitant csDMARD (MTX, leflunomide, hydroxychloroquine or sulfasalazine) at the time of study entry
9. Patient who is currently receiving or has received csDMARDs (eg, gold salts, cyclosporine, azathioprine, or any other immunosuppressives) other than MTX (up to 25 mg/week), leflunomide (up to 20 mg/day), hydroxychloroquine (up to 400 mg/day), or sulfasalazine (up to 3000 mg/day) within 4 weeks prior to study entry.
10. Patient who has received any parenteral corticosteroid administered by intramuscular or intravenous injection within 4 weeks prior to study entry, or is anticipated to require parenteral injection of corticosteroids during the study
11. Patient who had 3 or more joints injected with intraarticular corticosteroids or hyaluronic acid within 4 weeks prior to study entry. Joints injected with intraarticular corticosteroids or hyaluronic acid within 2 weeks prior to study entry or within 6 weeks prior to planned randomization cannot be counted in the TJC and SJC for entry or enrollment purpose
12. Patient with haemoglobin less than 80 g/L, absolute lymphocyte count lower than 0.5×109/L, absolute neutrophil count less than 1×109/L, or platelet count less than 100×109/L; clearance creatinine less than 60 mL/min; total bilirubin more than 1,5 times the upper limit of normal (ULN) at screening, aspartate aminotransferase, or alanine amino-transferase more than 2 times the upper limit of normal (ULN) at screening
13. Patient with co-administration with OAT3 inhibitors with a strong inhibition potential (such as probenecid).
14. Patient who has a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute a risk when taking investigational product or could interfere with the interpretation of data
15. Patient with an history of Stevens-Johnson syndrome and/or cutaneous vasculitis.
16. Patient with an history of CNS demyelinating disorders and peripheral demyelinating polyneuropathies.
17. Patient with an history of Moderate to severe heart failure (NYHA classes III/IV)
18. Patient with an history of Major Adverse Cardiovascular Events (non-fatal myocardial infarction or non-fatal stroke).
19. Patient who has a history of VTE (DVT/PE) within 12 weeks prior to randomization or have a history of recurrent (>1) VTE (DVT/PE). Prior DVT with PE where events overlapped in time (i.e., with PE considered resulting from DVT) is not considered recurrent DVT/PE for the purpose of this criterion
20. Patient who has been exposed to a live vaccine within 12 weeks prior to planned randomization or are expected to need/receive a live vaccine during the course of the study (with the exception of herpes zoster vaccination). Investigators should review the vaccination status of their patients and follow the local guidelines for adult vaccination with nonlive vaccines intended to prevent infectious disease prior to entering patients into the study
21. Patient with an active cancer
22. Patient with malignancy or history of malignancy.
23. Patient who has a current or recent (<30 days prior to study entry) clinically serious viral, bacterial, fungal, or parasitic infection.
24. Patient who is immunocompromised and, in the opinion of the investigator, is at an unacceptable risk for participating in the study.
25. Patient with an history of sepsis or risk of sepsis.
26. Patient with a history of active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
27. Patient who had household contact with a person with active tuberculosis (TB) and did not receive appropriate and documented prophylaxis for TB.
28. Patient who has evidence of active TB or has previously had evidence of active TB and did not receive appropriate and documented treatment.
29. Patient who has evidence of latent TB (as documented by a positive PPD, no clinical symptoms consistent with active TB, and a normal chest x-ray at screening) unless patient completes at least 3 weeks of appropriate treatment prior to study entry and agrees to complete the remainder of treatment while in the trial
30. Patient who had any major surgery within 8 weeks prior to study entry or will require major surgery during the study that, in the opinion of the investigator, would pose an unacceptable risk to the patient.
31. Pregnant or breastfeeding woman, or woman of childbearing potential who refuses to use an effective contraception during the study course, and who does not take an effective contraception at least one week after baricitinib treatment, five months after adalimumab treatment and three weeks after etanercept treatment.
32. Patient governed by articles L 1121-5 to L 1121-8 (persons deprived of their liberty by a judicial or administrative decision, minors, persons of legal age who are the object of a legal protection measure or unable to express their consent).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients who achieve an ACR 50 response at week 24 in each treatment group (COMBI group (adalimumab + baricitinib) vs. MONO group (baricitinib conventional therapy)

Secondary endpoints 12

1. Main secondary endpoints : Proportion of AEs and SAEs in each treatment group
2. Proportion of patients who achieve an ACR20 response and an ACR70 response at weeks 4, 12 and 24 in each treatment group
3. Proportion of patients who achieve an ACR50 response at weeks 4 and 12 in each treatment group
4. Proportion of patients who present a EULAR response at weeks 4, 12 and 24, according to DAS28-ESR, in each treatment group
5. Proportion of patients who achieve remission or low disease activity at weeks 4, 12 and 24, according to DAS28-ESR, in each treatment group
6. Quantitative change in DAS28-ESR, DAS28-CRP, sDAI and cDAI scores between baseline and each visit (until week 24 included) for each treatment group of treatment
7. Drug retention rates at weeks 4, 12 and 24 in each treatment group
8. Proportion of patients who decrease the glucocorticosteroid dose ≤ 5 mg per day, sustained from week 12 to week 24, among patients with a baseline dose > 5 mg per day, in each treatment group
9. Quantitative change in patient-reported outcomes (HAQ, FACIT, RAID) between baseline, weeks 4, 12 and 24 visit in each treatment group
10. Proportion of participants maintaining an ACR50 response, remission or low disease activity at week 52 in each treatment group.
11. Quantitative change in DAS28-ESR, DAS28-CRP, sDAI and cDAI scores between weeks 24 and 52 in each treatment group.
12. Main secondary endpoints : Quantitative change in DAS28-CRP, between baseline and week 24 for each treatment group of treatment

Investigational products

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

Test 3

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Bordeaux

Sponsor organisation

Centre Hospitalier Universitaire De Bordeaux

Address

12 Rue Dubernat, Cs 91286 Cs 91286

City

Talence

Postcode

33400

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Bordeaux

Contact name

Coordinating Investigator

Public contact point

Organisation

Centre Hospitalier Universitaire De Bordeaux

Contact name

Coordinating Investigator

Locations

1 EU/EEA country · 35 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

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

Documents 9 files

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

Application history

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