COMET: Comparison of Azathioprine to Methotrexate in Combination Therapy With Adalimumab in Crohn's Disease: an Open-label Randomized Controlled Trial

Sponsor

Centre Hospitalier Universitaire, Amiens (Other)

Overall Status

Recruiting

CT.gov ID

NCT05040464

Collaborator

(none)

166

Enrollment

Location

Arms

30.2

Anticipated Duration (Months)

5.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Combination therapy, the association of an anti-Tumor Necrosis Factor (TNF) to an immunosuppressant, is recognized as the most effective treatment during Crohn's disease (CD). Several mechanisms have been proposed to explain the superiority of combination therapy over monotherapy, the additive effect of two effective drugs or the prevention of anti-TNF immunogenicity. As the best combination therapy is unknown, both azathioprine (AZA) and methotrexate (MTX) are used. Some retrospective studies suggest a higher effectiveness of AZA. MTX may have an advantage in terms of safety.

The investigators hypothesize that AZA is more effective than MTX as combination therapy with adalimumab to improve short-term endoscopic, clinical and pharmacological outcomes in CD patients.

Condition or Disease	Intervention/Treatment	Phase
Crohn Disease Azathioprine Methotrexate	Drug: AZA capsules Drug: MTX Biological: blood sample	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

166 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Comparison of Azathioprine to Methotrexate in Combination Therapy With Adalimumab in Crohn's Disease: an Open-label Randomized Controlled Trial

Actual Study Start Date :

Aug 26, 2021

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZA group Combination of sub-cutaneous administration of adalimumab at a dose of 160mg(W0)-80mg(W2)-40mg(W6) and then 40mg EOW and oral AZA capsules at a daily dose of 2.5 mg/kg	Drug: AZA capsules oral AZA capsules at a daily dose of 2.5 mg per kilogram, Biological: blood sample The lab tests are: serum albumin, C-reactive protein, thrombocytosis and haemoglobin.
Experimental: MTX group Combination of sub-cutaneous administration of adalimumab at a dose of 160mg (week (W) 0)-80mg(W2)-40mg(W6) and then 40mg EOW and sub-cutaneous MTX 25mg once a week	Drug: MTX MTX 25 mg SC once a week Biological: blood sample The lab tests are: serum albumin, C-reactive protein, thrombocytosis and haemoglobin.

Arm

Intervention/Treatment

Experimental: AZA group

Combination of sub-cutaneous administration of adalimumab at a dose of 160mg(W0)-80mg(W2)-40mg(W6) and then 40mg EOW and oral AZA capsules at a daily dose of 2.5 mg/kg

Drug: AZA capsules

oral AZA capsules at a daily dose of 2.5 mg per kilogram,

Biological: blood sample

The lab tests are: serum albumin, C-reactive protein, thrombocytosis and haemoglobin.

Experimental: MTX group

Combination of sub-cutaneous administration of adalimumab at a dose of 160mg (week (W) 0)-80mg(W2)-40mg(W6) and then 40mg EOW and sub-cutaneous MTX 25mg once a week

Drug: MTX

MTX 25 mg SC once a week

Biological: blood sample

The lab tests are: serum albumin, C-reactive protein, thrombocytosis and haemoglobin.

Outcome Measures

Primary Outcome Measures

Variation of the endoscopic response between AZA and MTX groups [26 weeks]
Variation of the endoscopic response to AZA in combination with adalimumab and to MTX in combination with adalimumab in patients with CD. The endoscopic reference score (EREFS) is used to determine severity of 5 endoscopic findings: edema, rings, exudates, furrows, and structures. The EREFS classification system rates the severity of edema (0-2), rings (0-3), exudates (0-2), furrows (0-2), and strictures (0-1)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female patients with age > 18 years
Crohn's disease for at least 6 weeks,
Clinically active with CDAI > 150
Active inflammation by endoscopy (CDEIS > 4) at baseline
Not responder to conventional therapy or are intolerant to or have medical contraindications for such therapies and initiating treatment with adalimumab
Patient followed in a center belonging to the GETAID network
Fertile men and women of childbearing potential included in the protocol should use adequate methods of contraception according to study drug SMPCs.
Written consent

Exclusion Criteria:

Short bowel syndrome, ostomy, symptomatic stricture, abscess, recent history of abdominal surgery (<3 months)
Non-passable colonic stricture
Previous intolerance to thiopurines or MTX
Previous exposition to adalimumab
Contra-indication to immunosuppressants or anti-TNF
Others serious simultaneous illness that could interfere with study participation
Planning pregnancy, pregnancy or lactation or absence of contraception
Known substance abusers
Use of any investigational drug within 30 days
Adults protected by law