RCT part: COBRA-Slim with or without fast access to TNF blockade for remission induction in early RA. LTE part: Long Term observational follow-up on patients started in CareRA2020 RCT (COBRA Slim with or without fast access to TNF blockade for remission induction in RA).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UZ Leuven

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

15 May 2018 → 8 Jul 2025

Decision date (initial)

2024-02-01

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

BELGIAN HEALTH CARE KNOWLEDGE CENTER (KCE), RIZIV-INAMI (Belgium)

External identifiers

EU CT number

2023-510189-28-00

EudraCT number

2017-004054-41

ClinicalTrials.gov

NCT03649061

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

RCT part:
The primary objective is to compare in an early RA population with insufficient response (not achieving DAS28CRP≤3.2 within 32 weeks or DAS28CRP<2.6 at week 32) 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 week 8 up to week 32, versus further treatment adaptation according to the standard COBRA-Slim strategy.
For this purpose, the area under the DAS28CRP curve from BL until w104 will be assessed.
This outcome parameter is considered to be clinically very relevant, since it reflects the overall evolution in disease burden over the first 2 years of treatment, taking into account the speed and stability of the response and the need for consecutive treatment adaptations.

LTE part:
To evaluate the clinical disease course and safety for three years following participation of RA patients in the CareRA2020 RCT depending on the original treatment allocation.

Secondary objectives 1

1. Main secondary objective for the RCT part: 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.

Conditions and MedDRA coding

Rheumatoid Arthritis

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Belgian Health Care Knowledge Centre

EMA paediatric investigation plan (PIP)

EMEA-000299-PIP08-03

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Diagnosis of RA as defined by the ACR/EULAR2010 criteria for early RA
2. Early RA defined by a diagnosis made ≤ 1 year ago.
3. Use a reliable method of contraception for women of childbearing potential to be evaluated as in daily clinical practice
4. Able and willing to give written informed consent and to participate in the study
5. Understanding and able to write Dutch or French
6. for the LTE part: Patients participated in the CareRA2020 RCT, who completed w104 of the RCT and are able and willing to give written informed consent can participate in this long term observational follow-up.

Exclusion criteria 15

1. Previous treatment with: MTX or leflunomide; cyclophosphamide, azathioprine or cyclosporine; sulfasalazine (SSZ) for more than 3 weeks; hydroxychloroquine for more than 6 weeks; oral GC for more than 4 weeks within 4 months before screening; oral GC at a daily dosage of more than 10 mg prednisone equivalent within 4 weeks before baseline; oral GC at a daily dosage equal to or less than 10 mg prednisone equivalent within 2 weeks before baseline; intra-articular, intravenous or intramuscular GC within 4 weeks before BL; an investigational drug for the treatment/prevention of RA
2. History of chronic heart failure
3. History of severe infections or chronic infection
4. History of malignant neoplasm within 5 years
5. Contra indications for GC
6. Contra indications for TNF blocking agents
7. Contra indications for MTX or leflunomide
8. Psoriatic Arthritis
9. 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
10. Pregnancy, breastfeeding or no use of a reliable method of contraception for woman of childbearing potential (as in daily clinical practice)
11. Alcohol or drug abuse
12. Active TB
13. Latent TB unless adequate prophylactic treatment is given according to local guidelines
14. No access to the Belgian Health Insurance system
15. For the LTE part: No exclusion criteria are applicable.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. For the RCT part: Area under the curve of DAS28CRP over 104 weeks (long term effectiveness) in insufficient responders randomized to either COBRA-Slim Bio-Induction or Standard COBRA-Slim Induction.
2. For the LTE part: Area under the curve of DAS28-CRP over 260 weeks (long term effectiveness) in insufficient responders randomized to either COBRA-Slim Bio-Induction or Standard COBRA-Slim Induction.

Secondary endpoints 3

1. For the RCT part: 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.
2. For the RCT part: 1. Clinical efficacy: Remission (DAS28CRP<2.6) at w104, EULAR response at 28 weeks after randomization and at w104, 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.
3. For the LTE part: 1. To further determine the clinical efficacy of the accelerated access to Etanercept strategy versus the classic COBRA Slim strategy; 2. To evaluate the safety of the given treatments.

Investigational products

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

Test 2

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

Sponsor organisation

UZ Leuven

Address

Herestraat 49

City

Leuven

Postcode

3000

Country

Belgium

Scientific contact point

Organisation

UZ Leuven

Contact name

Patrick Verschueren

Public contact point

Organisation

UZ Leuven

Contact name

Patrick Verschueren

Locations

1 EU/EEA country · 21 investigational sites

By country

Investigational sites

Country notifications

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

Application history

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