COBRA-Slim with or without fast access to TNF blockade for remission induction in early RA

• Register: EUCTR
• Last refreshed on: 26 February 2024
• Main ID: EUCTR2017-004054-41-BE
• Date of registration: 15/03/2018
• Prospective Registration: Yes
• Primary sponsor: University Hospitals Leuven
• Public title: COBRA-Slim with or without fast access to TNF blockade for remission induction in early RA
• Scientific title: CareRA2020: Effectiveness of a combination of Methotrexate and a step down glucocorticoid regimen (COBRA-Slim) for remission induction in patients with early Rheumatoid Arthritis (RA), with or without fast access to 24 weeks of Tumor Necrosis Factor (TNF) blockade in insufficient responders, a randomized, multicenter, pragmatic trial. - CareRA2020
• Date of first enrolment: 07/05/2018
• Target sample size: 440
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004054-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: prospective study to evaluate the role of a biological in a remission induction scheme If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Belgium

Contacts

• Name: Patrick Verschueren
• Affiliation: University Hospitals Leuven

• Name: Patrick Verschueren
• Affiliation: University Hospitals Leuven

Key inclusion & exclusion criteria

Inclusion criteria:
- Age 18 years and older
- Diagnosis of RA as defined by the ACR/EULAR2010 criteria for early RA
- Early RA defined by a diagnosis made = 1 year ago.
- Use a reliable method of contraception for women of childbearing potential
- Able and willing to give written informed consent and to participate in the study
- Understanding and able to write Dutch or French

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 385
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 55

Exclusion criteria:
- Previous treatment with:
o MTX or leflunomide
o cyclophosphamide, azathioprine or cyclosporine
o sulphasalazine (SSZ) for more than 3 weeks
o hydroxychloroquine for more than 6 weeks
o oral GC for more than 4 weeks within 4 months before screening
o oral GC at a daily dosage of more than 10 mg prednisone equivalent within 4 weeks before baseline
o oral GC at a daily dosage equal to or less than 10 mg prednisone equivalent within 2 weeks before baseline
o intra-articular GC within 4 weeks before BL
o an investigational drug for the treatment/prevention of RA
- History of chronic heart failure
- History of severe infections or chronic infection
- History of malignant neoplasm within 5 years
- Contra indications for GC
- Contra indications for TNF blocking agents
- Contra indications for Methotrexate
- Psoriatic Arthritis
- Underlying cardiac, pulmonary, metabolic, renal or gastrointestinal conditions, chronic or latent infectious diseases or immune deficiency which in the opinion of the investigator places the patient at an unacceptable risk for participation in the study
- Pregnancy, breastfeeding or no use of a reliable method of contraception for woman of childbearing potential
- Alcohol or drug abuse
- Active TB
- Latent TB unless adequate prophylactic treatment is given
- No access to the Belgian Health Insurance system



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

early active Rheumatoid Arthritis, previously untreated with DMARDs
MedDRA version: 20.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Name: etanercept
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: ETANERCEPT
CAS Number: 185243-69-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Pharmaceutical Form: Coated tablet
INN or Proposed INN: LEFLUNOMIDE
CAS Number: 75706-12-6
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 10-20

Primary Outcome(s)

Secondary Objective: Main secondary objective
To investigate in insufficient responders to the COBRA-Slim regimen if accelerated access to a six-month course of anti-TNF therapy (etanercept), is leading to improved remission rates when compared to conventional treatment adaptation according to the COBRA-Slim strategy, 28 weeks after randomization into one of two treatment arms.

Other secondary objectives:
1.To further determine the clinical efficacy of accelerated access to etanercept versus the standard COBRA-Slim strategy in terms of remission rates and functionality scales.
2.To compare radiographic progression between all treatment schemes.
3.To evaluate the side effects of the given treatments as evaluated according to the regulatory guidelines for marketed products.
4.To evaluate the primary outcome using the DAS28ESR instead of the DAS28CRP.

Primary end point(s): Area under the curve of DAS28-CRP over 104 weeks (long term effectiveness) in insufficient responders randomized to either COBRA-Slim Bio-Induction or Standard COBRA-Slim Induction.

Main Objective: The primary objective is to compare in an early RA population with insufficient response (not achieving DAS28CRP=3.2 within 32 weeks) to COBRA-Slim remission induction, the long term effectiveness of accelerated access to a six-month course of anti-TNF therapy (etanercept) within a time window from w8 up to w32, versus further treatment adaptation according to the standard COBRA-Slim strategy.

Timepoint(s) of evaluation of this end point: at week 104

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: at 28 weeks after randomisation;
at week 52;
at week 64;
at week104

Secondary end point(s): Main secondary outcome measure
Proportion of insufficient responders achieving remission (DAS28CRP<2.6) 28 weeks after randomization (short term efficacy) to either COBRA-Slim Bio-Induction or Standard COBRA-Slim Induction.
Other secondary outcome measures
The following analyses will be performed in the randomized early insufficient responder population (w8-w32) with or without accelerated access to a six-month course of etanercept. The same analyses will also be performed including the randomized groups of insufficient responders, each completed with an early responder control population.

1. Clinical efficacy:
o Remission (DAS28CRP<2.6) at w104.
o EULAR response at 28 weeks after randomization and at w104
o HAQ response at 28 weeks after randomization and at w104
2. Radiographic progression: X-ray evolution at w52 and w104 compared to BL as reviewed and evaluated by the central team.
3. Side effects: (S)ARs from BL until w104
4. To evaluate the primary outcome using the DAS28ESR instead of the DAS28CRP.

Secondary ID(s)

KCE-16002

Source(s) of Monetary Support

Belgian Health Care Knowledge Center (KCE)

Ethics review

Status: Approved
Approval date: 07/05/2018
Contact:

Results

• Results available: Yes
• Date Posted: 19/08/2023
• Date Completed: 01/07/2022
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004054-41/results