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

Primary Purpose

Crohn Disease, Azathioprine, Methotrexate

Status

Recruiting

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

AZA capsules

MTX

blood sample

About this trial

This is an interventional treatment trial for Crohn Disease focused on measuring Crohn Disease, Combinations of therapy, anti-Tumor Necrosis Factor, azathioprine, methotrexate

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

CHU AmiensRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

AZA group

MTX group

Arm Description

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

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

Outcomes

Primary Outcome Measures

Variation of the endoscopic response between AZA and MTX groups

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)

Secondary Outcome Measures

Full Information

NCT ID

NCT05040464

First Posted

August 26, 2021

Last Updated

February 7, 2023

Sponsor

Centre Hospitalier Universitaire, Amiens

1. Study Identification

Unique Protocol Identification Number

NCT05040464

Brief Title

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

Acronym

COMET

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 26, 2021 (Actual)

Primary Completion Date

August 2023 (Anticipated)

Study Completion Date

March 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Centre Hospitalier Universitaire, Amiens

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Crohn Disease, Azathioprine, Methotrexate

Keywords

Crohn Disease, Combinations of therapy, anti-Tumor Necrosis Factor, azathioprine, methotrexate

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

166 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

AZA group

Arm Type

Experimental

Arm Description

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

Arm Title

MTX group

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

AZA capsules

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

MTX

Intervention Description

MTX 25 mg SC once a week

Intervention Type

Biological

Intervention Name(s)

blood sample

Intervention Description

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

Primary Outcome Measure Information:

Title

Variation of the endoscopic response between AZA and MTX groups

Description

Time Frame

26 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Mathurin Fumery, Pr

Phone

03 22 08 88 51

Fumery.mathurin@chu-amiens.fr

Facility Information:

Facility Name

CHU Amiens

City

Amiens

ZIP/Postal Code

80480

Country

France

Individual Site Status

Recruiting

Facility Contact: