Efficacy of a sequential treatment strategy in Rheumatoid Arthritis.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Montpellier

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Immune System Diseases [C20]

Trial duration

28 Nov 2022 → ongoing

Decision date (initial)

2022-07-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS · BMS

External identifiers

EU CT number

2022-500234-29-00

ClinicalTrials.gov

NCT05428488

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To compare the percentage of remission (DAS28-CRP<2.6) obtained during the 36 weeks following randomization, with a sequential therapeutic strategy using abatacept versus a routine strategy continuing TNF inhibitors (TNFi), in ACPA positive RA patients responding to a first TNFi, initiated 12 weeks before randomization

Secondary objectives 11

1. To compare between the 2 groups of treatment at 12, 24 and 36 weeks after randomization the proportion of patients in remission using different definitions
2. To compare between the 2 groups of treatment at 12, 24 and 36 weeks after randomization the proportion of patients in low disease activity using different definitions
3. To compare between the 2 groups of treatment at 12, 24 and 36 weeks after randomization the proportion of responders on EULAR response criteria
4. To compare between the 2 groups of treatment at 12, 24 and 36 weeks after randomization the variations of patient-reported outcomes
5. To compare between the 2 groups of treatment at 12, 24 and 36 weeks after randomization the variations of auto-antibodies titers (RF and ACPA) compared to baseline and association with remission.
6. To compare between the 2 groups of treatment at 12, 24 and 36 weeks after randomization the number of flares using the FLARE self-questionnaire
7. To compare between the 2 groups of treatment the 36 weeks cumulative dose of steroids
8. To compare between the 2 groups of treatment the 36 weeks cumulative serious adverse events including severe infections
9. To compare between the 2 groups of treatment the 36 weeks cumulative cost-effectiveness.
10. To compare between the 2 groups of treatment at 48-weeks the radiographic progression compared to baseline
11. To compare between the 2 groups of treatment at 48-weeks the allocated treatment retention.

Conditions and MedDRA coding

Rheumatoid Arthritis

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Aged 18 years or above
2. Rheumatoid Arthritis according to ACR-EULAR 2010
3. ACPA positive
4. Under methotrexate or leflunomide treatment for at least 3 months
5. DAS28-CRP>3.2 under methotrexate or leflunomide calculated with CRP dated less than 7 days from baseline
6. Escape under synthetic background treatment defined by an elevation of CRP (CRP> 5mg/L ) or ESR (for men: > age in years/2 ; for women: > age (+10) /2)) within the last 6 months before baseline
7. Targeted DMARDs (biological and targeted synthetic DMARDs) naïve
8. Indication for a TNF inhibitor

Exclusion criteria 9

1. Contra-indications to a TNF inhibitor and/or Abatacept
2. Dementia
3. Fibromyalgia
4. Absence of tuberculosis screening in the previous 3 months before baseline
5. Drug addiction, addiction to alcohol
6. Subject with moderate to severe heart failure (class 3 or class 4 cardiac disease as defined by the New York Heart Association Functional Classification)
7. Known allergy or intolerance to an anti-TNF therapy
8. Patient with untreated active hepatitis B
9. Patient vaccinated with a live vaccine within 30 days prior to screening

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of patients in remission defined by DAS28-CRP<2.6 score during the 36 weeks of treatment following randomization using a mixed logistic regression model for repeated data

Secondary endpoints 11

1. Percentage of patients in remission using different definitions: DAS28-ESR<2.6, CDAI≤2.8, SDAI≤3.3 and Boolean criteria (number of tender and swollen joint, visual analogue scale for global health and CRP all ≤1)
2. Percentage of patients in remission using different definitions at 12, 24 and 36 weeks after randomization: DAS28-ESR<2.6, CDAI≤2.8, SDAI≤3.3 and Boolean criteria (number of tender and swollen joint, visual analogue scale for global health and CRP all ≤1)
3. Proportion of responders using EULAR definition (variations of DAS28-CRP from baseline >0.6 and DAS28-CRP≤5.1) at 12, 24 and 36 weeks after randomization
4. Values and variations from baseline of patient-reported outcomes including health-assessment questionnaire (HAQ-DI), EQ5D, SF-36 (SF-6D)
5. Variation of auto-antibodies titles (RF and ACPA) and correlation of these variations with remission rate defined by DAS28-CRP<2.6
6. Frequency of flares assessed using the FLARE-RA questionnaire completed by the patient between visits
7. Cumulative doses of steroids collected with a booklet between 12 weeks and 48 weeks visits
8. Safety: rates of serious adverse events including severe infections between randomization visit (W12) and 48 weeks
9. Cost efficacy analysis based on direct and indirect costs and QALY between randomization visit (W12) and 48 weeks
10. Variations Sharp modified by Van der Heidje score between baseline and 48 weeks
11. Percentage of patients remaining on abatacept in the sequential arm and on the 1st TNF inhibitor in the control arm at 48 weeks

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Montpellier

Sponsor organisation

Centre Hospitalier Universitaire De Montpellier

Address

191 Avenue Du Doyen Gaston Giraud

City

Montpellier Cedex 5

Postcode

34295

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Montpellier

Contact name

Jacques MOREL

Public contact point

Organisation

Centre Hospitalier Universitaire De Montpellier

Contact name

Jacques MOREL

Locations

1 EU/EEA country · 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 36 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