Assessment of Mucosal Activity to Improve the Prognosis of Patients With Crohn's Disease Treated With Immunosuppressants

NCT ID: NCT01562951

Last Updated: 2016-05-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2014-03-31

Brief Summary

This study will test that individualized treatment in patients with Crohn's Disease in remission or mild clinical activity under immunosuppressants may improve prognosis, rather than just treating flares.

Detailed Description

Patients will be prescreened for inclusion criteria one week before the start of screening at Visit 0 (Prescreening Visit). Patients must be on stable doses of azathioprine/mercaptopurine. Patients will be given a diary to record their CD symptoms for the seven days prior to Visit 1. At Visit 1 (Screening Visit 1), patients will have their CDAI score assessed based upon their diary information. Patients with CDAI ≤ 220 will then have both calprotectin and hsCRP testing done. Patients with calprotectin > or = 250µg/g and/or hsCRP > or = 5mg/L will be notified and told to schedule Visit 2 within three weeks. At Visit 2 (Screening Visit 2), patients will undergo a colonoscopy. A Crohn's Disease Endoscopic Index of Severity (CDEIS) will be used to determine the endoscopic activity. Patients with significant endoscopic lesions will be notified and asked to enroll in the study.

Patients will be randomized into the study at Visit 3 (Randomization Visit, same day of Visit 2 in results available). Due to the cost and invasiveness of the colonoscopy, the Screening Visit 2 colonoscopy will serve as the baseline for the study, should the patient be enrolled. Drug will also be dispensed at this visit. Eligible patients will be randomized in a 1:1 ratio to receive either adalimumab or placebo during the treatment period, along with continuing their current immunosuppressive maintenance treatment at a stable dose. Treatment in both arms will be induction at 160/80mg and maintenance on 40 mg every other week.

Patients will return for follow up visits every 12 weeks until the final follow-up visit at 48 weeks (Visit 7), where another colonoscopy will be performed. Patients who terminate early from the study for any reason will be asked to return for a follow-up visit, where Visit 7 procedures will be performed.

Before week 48, if a patient has an increase of more than 50% in either calprotectin and/or hsCRP over baseline and above the thresholds at any regular visit, a follow-up visit will be performed two weeks later. If the 50% increase is still observed another colonoscopy will be performed, within two weeks of the follow-up visit. If patients still have significant endoscopic lesions, study product will be intensified to 40 mg weekly. This will include patients on placebo in order to preserve the double-blind aspect of the study.

Conditions

Crohn's Disease; Mucosal Inflammation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

PLACEBO

Treatment with placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

PLACEBO at 160/80 mg and maintained on 40 mg eow until next colonoscopy performed at week 48. If before week 48, an increase of more than 50% is observed in calprotectin and/or hsCRP from baseline, over two consecutive follow up visits 2 weeks apart, the colonoscopy will be performed earlier. If patients have still significant endoscopic lesions, adalimumab or adalimumab placebo will be intensified to 40 mg weekly

ADALIMUMAB

Treatment with Adalimumab

Group Type: ACTIVE_COMPARATOR

ADALIMUMAB

Intervention Type: DRUG

Adalimumab at 160/80 mg and maintained on 40 mg eow until next colonoscopy performed at week 48. If before week 48, an increase of more than 50% is observed in calprotectin and/or hsCRP from baseline, over two consecutive follow up visits 2 weeks apart, the colonoscopy will be performed earlier. If patients have still significant endoscopic lesions, adalimumab or adalimumab placebo will be intensified to 40 mg weekly.

Interventions

ADALIMUMAB

Adalimumab at 160/80 mg and maintained on 40 mg eow until next colonoscopy performed at week 48. If before week 48, an increase of more than 50% is observed in calprotectin and/or hsCRP from baseline, over two consecutive follow up visits 2 weeks apart, the colonoscopy will be performed earlier. If patients have still significant endoscopic lesions, adalimumab or adalimumab placebo will be intensified to 40 mg weekly.

Intervention Type: DRUG

Placebo

PLACEBO at 160/80 mg and maintained on 40 mg eow until next colonoscopy performed at week 48. If before week 48, an increase of more than 50% is observed in calprotectin and/or hsCRP from baseline, over two consecutive follow up visits 2 weeks apart, the colonoscopy will be performed earlier. If patients have still significant endoscopic lesions, adalimumab or adalimumab placebo will be intensified to 40 mg weekly

Intervention Type: DRUG

Other Intervention Names

HUMIRA

Eligibility Criteria

Inclusion Criteria

• Age 18-75 years old- Patients with CD diagnosis confirmed by colonoscopy
• Patients with inflammatory CD of terminal ileal, colonic or ileocolonic location
• Maintenance treatment with at least 2 mg/kg/day for azathioprine/ 1 mg/kg/day for mercaptopurine or the highest dosage tolerated in patients who could not tolerate this dosage, at least 6 months.
• Willingness to sign informed consent
• If female of childbearing age, be post-menopausal, surgically sterile, or willing to use a reliable form of birth control for the duration of the study (such as physical barrier [patient and partner], contraceptive pill or patch, spermicide and barrier, or intrauterine device)and for at least five months after the last adalimumab treatment.
• Able to comply with the requirements of the study.
• CDAI score ≤ 220.
• Calprotectin > or = 250µg/g and/or hsCRP > or = 5mg/L.
• Significant lesions seen during colonoscopy, as defined by CDEIS.

Exclusion Criteria

• Patients with an ostomy, or ileoanal pouch (subject with previous ileo-rectal anastomosis are not excluded), draining fistula, abscess
• Patients who had intestinal resection within one year.
• Symptomatic stricture either diagnosed by colonoscopy or clinically suspected and confirmed by imaging techniques.
• Prior treatment with any anti-tumor necrosis factor (TNF) drug.
• Patients receiving rectal treatment 1 month before inclusion
• Signs of active infection
• Previous history of active untreated or inadequately treated tuberculosis (TB) or latent TB. Patients should be screened for latent TB as per local guidelines or clinical practice in the country of study conduct. Patients with latent TB should be treated with standard antimycobacterial therapy (for at least 4 weeks) before initiating biologic therapy and have a negative CRX for active TB at screening
• Subjects with a poorly controlled medical condition such as: uncontrolled diabetes with documented history of recurrent infections, unstable ischemic heart disease, moderate to severe congestive heart failure (New York Heart Association [NYHA] class III or IV), recent cerebrovascular accident, or any other condition which, in the opinion of the Investigator or the sponsor, would put the subject at risk by participation in the protocol
• Signs of colon cancer or dysplasia
• Signs of severe or unstable renal, hepatic, gastrointestinal, cardiovascular, respiratory, neurological, psychiatric, or hematological disease
• Signs of cancer in the past five years, except for localized and treated basal cell skin cancer or cervical cancer
• Patients who are pregnant or nursing
• Concomitant treatment with:

• Live vaccines.
• 5-ASA compounds: Rectal 5-ASA should be discontinued at least 4 weeks before study inclusion. Oral 5-ASA must be at a stable dose for at least 4 weeks before study inclusion. If oral 5-ASA has recently been discontinued, 4 weeks should pass before study inclusion.
• Oral corticosteroids (eg., Prednisone, budesonide) should be discontinued for 3 months before study inclusion.
• Antibiotics for CD. Only antibiotics used to treat a concurrent infection are allowed.
• Immunomodulators:

Patients receiving therapy with azathioprine/mercaptopurine must have been on a stable dose for at least 12 weeks before inclusion and must continue with the same dose during the study.

No treatment with other known immunomodulators (eg. methotrexate, 6-thioguanine [6-TG], cyclosporine, tacrolimus, sirolimus, ustekinumab, pentoxifylline, or mycophenolate mofetil) or experimental drugs (eg., factor colony stimulating granulocyte macrophage [GM-CSF]) within 6 months

• Monoclonal antibodies or anti-TNF drugs.
• Aspirin or Non-steroidal anti-inflammatory drugs (NSAIDs). Treatment with aspirin and/or NSAIDS should not occur for more than 15 consecutive days before collecting of the stool sample for Calprotectin and performing the colonoscopy.

• Screening laboratory and other analyses show any of the following abnormal results:
• Aspartate transaminase (AST) or alanine transaminase (ALT) > 2 x the upper limit of the reference range;
• Total bilirubin ≥ 3 mg/dL (51 μmol/L);
• Serum creatinine > 1.6 mg/dL (144 μmol/L)

• History of any drug or alcohol abuse in the past 2 years
• Receipt of other study product within 3 months of inclusion in this study
• Patients employed by the sponsor or in any relationship of dependence with the sponsor and/or investigator
• Staff at the study center
• Hypersensitivity to the active substance or to any of the excipients

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa

OTHER

Sponsor Role: lead

Abbott

INDUSTRY

Sponsor Role: collaborator

TFS Trial Form Support

INDUSTRY

Sponsor Role: collaborator

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

VALLE GARCÍA, MD

Role: PRINCIPAL_INVESTIGATOR

Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa

Locations

Imeldaziekenhuis Bonheiden

Bonheiden, Bonheiden, Belgium

Hospital Erasme Bruxelles

Brussels, Brussels Capital, Belgium

Hospital Saint Luc Bruxelles

Brussels, Brussels Capital, Belgium

Hospital University Gent

Ghent, Gent, Belgium

Centre Hospitalier Universitaire de Liege

Liège, Liege, Belgium

Heiling Hartzieknhuis Roeselare

Roeselare, Roeselare, Belgium

CHU Amiens - Hospital Nord

Amiens, Amiens, France

CHU Bordeaux - Hospital Haut-Leveque

Pessac, Bordeaux, France

Hospital Beaujon

Clichy, Clichy, France

CHRU Lille - Hospital Claude Huriez

Lille, Lille, France

CHU Lyon Sud

Lyon, Lyon, France

CHU Nancy - Hospital de Brabois Adultes

Vandœuvre-lès-Nancy, Nancy, France

CHU Nantes

Nantes, Nantes, France

Hospital Saint Louis

Paris, Paris, France

CHRU Reims - Hospital Robert Debre

Reims, Reims, France

CHU Rouen - Hospital Charles Nicolle

Rouen, Rouen, France

CH Saint Etienne - Hospital Nord

Saint-Etienne, Saint Etienne, France

CHU Tours - Hospital Trousseau

Chambray, Tours, France

Complejo Hospitalario Santiago de Compostela

Santiago de Compostela, A coruña, Spain

Hospital Universitario Reina Sofia

Córdoba, Andalusia, Spain

Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Hospital Santa Creu i Sant Pau

Barcelona, Barcelona, Spain

Hospital Doctor Negrin

Las Palmas de Gran Canarias, Canary Islands, Spain

Hospital Universitario La Princesa

Madrid, Madrid, Spain

Hospital Gregorio Marañón

Madrid, Madrid, Spain

Hospital Ramón y Cajal

Madrid, Madrid, Spain

Hospital Virgen del Rocío

Seville, Sevilla, Spain

Hospital de Manises

Manises, Valencia, Spain

Hospital Clínico de Valencia

Valencia, Valencia, Spain

Hospital Lozano Blesa

Zaragoza, Zaragoza, Spain

Countries

Belgium; France; Spain

Other Identifiers

A12-771

Identifier Type: -

Identifier Source: org_study_id