Efficacy of Abatacept vs Adalimumab in Early, Autoantibody positive Rheumatoid Arthritis (RA) and who did not respond well to methotrexate.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bristol-Myers Squibb Services Unlimited Company

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

5 Nov 2021 → ongoing

Decision date (initial)

2024-01-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Bristol-Myers Squibb Services Unlimited Company

External identifiers

EU CT number

2023-506450-20-00

EudraCT number

2020-000350-96

WHO UTN

U1111-1247-1367

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To demonstrate the superiority in efficacy of abatacept compared with adalimumab, both on background MTX, in achieving clinical response (ACR50) at Week 24, in early, seropositive (RF+ and ACPA+) RA patients with the SE HLA Class II risk alleles (ie, SE+).

Secondary objectives 6

1. To compare the efficacy of abatacept with adalimumab, both on background MTX in achieving clinical remission criteria (DAS28-CRP remission) at Week 24 in early, seropositive RA patients with the SE HLA Class II risk alleles (ie, SE+).
2. To compare the efficacy of abatacept with adalimumab, both on background MTX in achieving clinical response (ACR50) at Week 24 in the whole study population of early, seropositive RA patients.
3. To compare the efficacy of abatacept with adalimumab, both on background MTX in achieving clinical remission criteria (CDAI remission) at Week 24 in early, seropositive RA patients with the SE HLA Class II risk alleles (ie, SE+).
4. To compare the efficacy of abatacept with adalimumab, both on background MTX in achieving improvement in pain at Week 24 in early, seropositive RA patients with the SE HLA Class II risk alleles (ie, SE+).
5. To determine the efficacy over time by treatment in early, seropositive RA patients (SE+ subset and whole population).
6. To determine the improvement in health-related quality of life over time by treatment in early, seropositive RA patients (SE+ subset and whole population).

Conditions and MedDRA coding

Rheumatoid Arthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Early rheumatoid arthritis (RA), defined as symptoms of RA that started ≤ 12 months prior to screening and satisfied the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria for the classification of RA at some point during the 12-month period
2. Naïve to any targeted (biologic or nonbiologic) disease-modifying antirheumatic drugs (DMARDs), conventional synthetic DMARDs other than methotrexate (MTX), or investigational therapies for RA
3. Treated with MTX for at least 12 weeks, with a stable dose of oral or parenteral MTX for at least 4 weeks prior to randomization
4. Anti-cyclic citrullinated peptide-2 (Anti-CCP-2) test that is > 3× the upper limit of normal and are positive for rheumatoid factor (RF) according to central lab testing during screening
5. At least a Disease Activity Score 28-joint count calculated using Creactive protein (DAS28-CRP) ≥ 3.2 at screening
6. At least 3 tender and at least 3 swollen joints at screening and at randomization.

Exclusion criteria 11

1. Women who are breastfeeding
2. Autoimmune disease other than RA (e.g., psoriasis, systemic lupus erythematosus [SLE], vasculitis, seronegative spondyloarthritis, inflammatory bowel disease, Sjogren's syndrome) or currently active fibromyalgia
3. History of or current inflammatory joint disease other than RA (e.g., psoriatic arthritis, gout, reactive arthritis, Lyme disease)
4. At risk for tuberculosis
5. Recent acute infection
6. History of chronic or recurrent bacterial infection (e.g., chronic pyelonephritis, osteomyelitis, bronchiectasis)
7. History of infection of a joint prosthesis or artificial joint
8. History of systemic fungal infections (such as histoplasmosis, blastomycosis, or coccidiomycosis)
9. History of primary immunodeficiency
10. Current clinical findings or a history of a demyelinating disorder
11. 5 or more joints cannot be assessed for tenderness or swelling

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of SE+ participants meeting ACR50 response at Week 24

Secondary endpoints 6

1. Proportion of SE+ participants achieving DAS28-CRP remission (DAS28-CRP < 2.6) at Week 24
2. Proportion of whole study population participants meeting ACR50 response at Week 24
3. Proportion of SE+ participants achieving CDAI remission (CDAI ≤ 2.8) at Week 24
4. Mean change from baseline in SE+ participant-reported pain (VAS) at Week 24
5. Proportion of SE+ subset and whole population achieving ACR20/50/70 responses, DAS remission, CDAI remission, SDAI remission over the SBTP and OLTP; mean changes from baseline in DAS28-CRP, CDAI, SDAI over the SBTP and OLTP; mean changes from baseline in the 7 ACR core components over the SBTP and OLTP
6. Mean change from baseline in SF-36 in SE+ subset and whole population at Week 24 and Week 104 (4 physical and 4 mental subscales and the physical component and mental component summary)

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bristol-Myers Squibb Services Unlimited Company

Sponsor organisation

Bristol-Myers Squibb Services Unlimited Company

Address

Plaza 254, Blanchardstown Corporate Park 2 Blanchardstown Corporate Park 2

City

Dublin 15

Postcode

D15 T867

Country

Ireland

Scientific contact point

Organisation

Bristol-Myers Squibb Services Unlimited Company

Contact name

GSM-CT

Public contact point

Organisation

Bristol-Myers Squibb Services Unlimited Company

Contact name

GSM-CT

Third parties 3

Locations

6 EU/EEA countries · 19 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 30 files

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

Application history

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