A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn's Disease Patients in Sustained Steroid-free Remission on Combination Therapy

NCT02177071 | Completed Phase 4 DMC

• 1 other identifier: GETAID 2014-03
• Study Type: interventional
• Target: 211
• Locations: 3 countries
• Sites: 27

Brief Summary

Phase IV Design : Prospective, open-label, randomized three-arms study Main Inclusion criteria Luminal Crohn's disease patients with steroid free remission for at least 6 months and a combination therapy with infliximab and anti-metabolites for at least 8 months Primary objective To demonstrate that Infliximab scheduled maintenance with or without antimetabolites is superior to antimetabolites alone to maintain sustained steroid-free remission over 2 years, while the latter is non inferior with regards to the mean time spent in remission over the same duration Main co-primary end points Clinical relapse rate at 2 years Mean remission duration within 2 years Study treatment Infliximab, Mercaptopurine, azathioprine, methotrexate. Number of subjects 225 randomized patients (75 per arm) Study duration: 3 + 2 years Enrollment: 3 years Follow-up: 2 years

Conditions

Crohn's Disease

Keywords

CROHN DISEASE; INFLIXIMAB; COMBINATION THERAPY; steroid free remission; anti-metabolites

Outcome Measures

Primary Outcomes (1)

• co-primary efficacy end points

  There will be two co-primary efficacy end points Relapse rate at 2 years, relapse being defined by either one of the following events: * A CDAI\>250 at any visit or between 150 and 250 with an increase of at least 70 points, over two consecutive visits one week apart associated with a CRP \> 5 mg/l or a fecal calprotectin \> 250 microg/g * A new opening fistula, perianal or entero-cutaneous. * An intra-abdominal abcess (size of at least 3 cm) or perianal abcess (size of at least 2 cm) * An episode of intestinal obstruction due to Crohn's lesions confirmed by medical imaging and requiring hospitalisation (also considered as treatment failure, see below) Mean restricted time spent in remission This time will be computed in all patients, from baseline (CDAI \<150 and with absence of fistula drainage) until relapse, as defined above, within the 2 first years. First and subsequent remissions will be summed up within the two first years.

  2 ans

Secondary Outcomes (5)

• relapse in each arm.

  2 years

• Sustained clinical remission

  2years

• Treatment failure

  2 years

• Tissue damage progression

  2 years

• Endoscopic remission

  2 years

Other Outcomes (4)

• disability index

  2 YEARS

• adverse events and SAE

  2 YEARS

• BIOLOGICS

  2 YEARS

Study Arms (3)

INFLIXIMAB AND ANTI METABOLITE

NO INTERVENTION

continuing scheduled infliximab treatment and anti-metabolite

STOP INFLIXIMAB CONTINUING ANTI METABOLITE

OTHER

discontinuing infliximab and continuing the anti-metabolite

Drug: INFLIXIMAB

CONTINUING INFLIXIMAB AND discontinuing anti-metabolites

OTHER

CONTINUING INFLIXIMAB AND DISCONTINUING ANTI METABOLITE

Drug: AZATHIOPRINE; Drug: MERCAPTOPURINE; Drug: Methotrexate

Interventions

INFLIXIMAB DRUG

STOP INFLIXIMAB CONTINUING ANTI METABOLITE

AZATHIOPRINE DRUG

CONTINUING INFLIXIMAB AND discontinuing anti-metabolites

MERCAPTOPURINE DRUG

CONTINUING INFLIXIMAB AND discontinuing anti-metabolites

Methotrexate DRUG

CONTINUING INFLIXIMAB AND discontinuing anti-metabolites

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Crohn's disease.
• Male or female, age \> 18 years.
• Currently treated with a combination therapy with infliximab and anti-metabolites for luminal Crohn's disease.
• Combined therapy with scheduled infliximab and anti-metabolites for at least 8 months.
• Scheduled administration of infliximab 5 mg/Kg every 8 weeks over the last 4 months.
• Antimetabolites administered at a stable dosage for the last 3 months: at least 1 mg/Kg or 2 mg/Kg for mercaptopurine and azathioprine, respectively, or the highest tolerated dosage if intolerance to standard dose; at least 15 mg/week subcutaneously for methotrexate.
• Patients in steroid free clinical remission for at least 6 months according to retrospective assessment of the patients' files.
• CDAI \< 150 at baseline.
• A contraceptive during the whole study for childbearing potential female patients.
• Patients able to understand the information provided to them and to give written informed consent for the study

You may not qualify if:

• Patients who have presented a severe acute or delayed reaction to infliximab.
• Perianal fistulae as the main indication for infliximab treatment
• Patients with ostomy or ileoanal pouch
• Pregnancy or planned pregnancy during the study
• Inability to follow study procedures as judged by the investigator
• Non-compliant subjects.
• Participation in another therapeutic study
• Steroid use ≤6 months prior to screening
• Currently receiving steroids, immunosuppressive agents (other than purine, methotrexate), biologic treatment (other than infliximab) or thalidomide

Sponsors & Collaborators

• Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives: lead
• Saint-Louis Hospital, Paris, France: collaborator

Study Sites (27)

St Vincent Hospital

Melbourne, Australia

Location

CHU LIEGE - Sart Tilman

Liège, Province De Liège, 4000, Belgium

Location

Gent University Hospital

Ghent, 9000, Belgium

Location

Chu Clermont-Ferrand

Clermont-Ferrand, Auvergne-Rhône-Alpes, 63003, France

Location

CHU LYON

Pierre-Bénite, Auvergne-Rhône-Alpes, 69495, France

Location

Chu Saint Etienne

Saint-Etienne, Auvergne-Rhône-Alpes, 42270, France

Location

Chu Besancon

Besançon, Bourgogne-Franche-Comté, 25030, France

Location

Chu Rennes

Rennes, Brittany Region, 35033, France

Location

Chu Tours

Tours, Centre-Val de Loire, 37044, France

Location

Chu Reims

Reims, Grand Est, 51092, France

Location

Chu Nancy

Vandœuvre-lès-Nancy, Grand Est, 54500, France

Location

Chu Amiens

Amiens, Hauts-de-France, 80054, France

Location

Chu Lille

Lille, Hauts-de-France, 59000, France

Location

Chr Valencienne

Valenciennes, Hauts-de-France, 59300, France

Location

Caen Unversity Hospital

Caen, Normandy, 14033, France

Location

CHU Bordeaux - Pessac

Pessac, Nouvelle-Aquitaine, 33700, France

Location

Chu Montpellier

Montpellier, Occitanie, 34295, France

Location

Chu Toulouse

Toulouse, Occitanie, 31403, France

Location

Chu Nantes

Nantes, Pays de la Loire Region, 44093, France

Location

CHU NICE

Nice, Provences Alpes Cote d'Azur, 06202, France

Location

Hopital Saint Joseph

Paris, 75014, France

Location

Hopital Beaujon

Clichy, Île-de-France Region, 92110, France

Location

Chu Kremlin Bicetre

Le Kremlin-Bicêtre, Île-de-France Region, 94270, France

Location

Hopital Bicetre

Le Kremlin-Bicêtre, Île-de-France Region, 94275, France

Location

Hopital Saint Louis

Paris, Île-de-France Region, 75010, France

Location

Hopital St Antoine

Paris, Île-de-France Region, 75012, France

Location

Montsouris Mutualist Institute

Paris, Île-de-France Region, 75674, France

Location

Related Publications (3)

• Pierre N, Huynh-Thu VA, Baiwir D, Mazzucchelli G, Fleron M, Trzpiot L, Eppe G, De Pauw E, Laharie D, Satsangi J, Bossuyt P, Vuitton L, Vieujean S, Colombel JF, Meuwis MA, Louis E; GETAID and the SPARE-Biocycle research group. External validation of serum biomarkers predicting short-term and mid/long-term relapse in patients with Crohn's disease stopping infliximab. Gut. 2024 Nov 11;73(12):1965-1973. doi: 10.1136/gutjnl-2024-332648.

  PMID: 39134391 DERIVED

• Louis E, Resche-Rigon M, Laharie D, Satsangi J, Ding N, Siegmund B, D'Haens G, Picon L, Bossuyt P, Vuitton L, Irving P, Viennot S, Lamb CA, Pollok R, Baert F, Nachury M, Fumery M, Gilletta C, Almer S, Ben-Horin S, Bouhnik Y, Colombel JF, Hertervig E; GETAID and the SPARE-Biocycle research group. Withdrawal of infliximab or concomitant immunosuppressant therapy in patients with Crohn's disease on combination therapy (SPARE): a multicentre, open-label, randomised controlled trial. Lancet Gastroenterol Hepatol. 2023 Mar;8(3):215-227. doi: 10.1016/S2468-1253(22)00385-5. Epub 2023 Jan 11.

  PMID: 36640794 DERIVED

• Hirten RP, Lakatos PL, Halfvarson J, Colombel JF. Reply. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1301-1302. doi: 10.1016/j.cgh.2020.07.061. Epub 2020 Nov 26. No abstract available.

  PMID: 33248096 DERIVED

MeSH Terms

Conditions

Crohn Disease

Interventions

Infliximab; Azathioprine; Mercaptopurine; Methotrexate

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Thionucleosides; Sulfur Compounds; Organic Chemicals; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Sulfhydryl Compounds; Aminopterin; Pterins; Pteridines

Study Officials

• David Laharie

  Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2014
• First Posted: June 27, 2014
• Study Start: October 9, 2015
• Primary Completion: June 1, 2021
• Study Completion: October 1, 2021
• Last Updated: August 3, 2022

Record last verified: 2022-08

Locations

FR (24); AU (1); BE (2)