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

NCT01562951 | Terminated Phase 3

• 1 other identifier: A12-771
• Study Type: interventional
• Target: 15
• Locations: 3 countries
• Sites: 30

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.

Conditions

Crohn's Disease; Mucosal Inflammation

Keywords

Crohn's disease; mucosal inflammation; lesions

Outcome Measures

Primary Outcomes (1)

• The primary efficacy endpoint is the rate of therapeutic failure up to week 48

  The therapeutic failure is defined as any of following cases: 1. CDAI \> 220 with at least 70-point increase from baseline over two consecutive visits 12 weeks apart or CDAI \> 300 at any time point during the study; 2. need of any change in therapy for CD except the ones planned per protocol in each group of the study; 3. need of surgery related to CD or of stricture endoscopic dilatation.

  Every 12 weeks up to Week 48

Secondary Outcomes (17)

• The rate of therapeutic failure (see the definition of primary endpoint) up to week 24

  up to week 24

• Change in CDEIS from baseline to week 48

  up to week 48

• The rate of mucosal healing (CDEIS=0) at week 48

  at week 48

• The rate of CDEIS remission (CDEIS<=3) at week 48

  at week 48

• The rate of CDEIS response, which is defined as a decrease of at least 4 points in CDEIS from baseline to week 48

  from baseline up to week 48

Study Arms (2)

PLACEBO

PLACEBO COMPARATOR

Treatment with placebo

Drug: Placebo

ADALIMUMAB

ACTIVE COMPARATOR

Treatment with Adalimumab

Drug: ADALIMUMAB

Interventions

ADALIMUMAB 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.

Also known as: HUMIRA

ADALIMUMAB

Placebo 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

PLACEBO

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• Antibiotics for CD. Only antibiotics used to treat a concurrent infection are allowed.
• Immunomodulators:

Sponsors & Collaborators

• Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa: lead
• Abbott: collaborator
• TFS Trial Form Support: collaborator

Study Sites (30)

Imeldaziekenhuis Bonheiden

Bonheiden, Bonheiden, 2820, Belgium

Location

Hospital Erasme Bruxelles

Brussels, Brussels Capital, 1070, Belgium

Location

Hospital Saint Luc Bruxelles

Brussels, Brussels Capital, 1200, Belgium

Location

Hospital University Gent

Ghent, Gent, 9000, Belgium

Location

Centre Hospitalier Universitaire de Liege

Liège, Liege, 4000, Belgium

Location

Heiling Hartzieknhuis Roeselare

Roeselare, Roeselare, 8800, Belgium

Location

CHU Amiens - Hospital Nord

Amiens, Amiens, 80054, France

Location

CHU Bordeaux - Hospital Haut-Leveque

Pessac, Bordeaux, 33604, France

Location

Hospital Beaujon

Clichy, Clichy, 92110, France

Location

CHRU Lille - Hospital Claude Huriez

Lille, Lille, 59037, France

Location

CHU Lyon Sud

Lyon, Lyon, 69495, France

Location

CHU Nancy - Hospital de Brabois Adultes

Vandœuvre-lès-Nancy, Nancy, 54500, France

Location

CHU Nantes

Nantes, Nantes, 44093, France

Location

Hospital Saint Louis

Paris, Paris, 75010, France

Location

CHRU Reims - Hospital Robert Debre

Reims, Reims, 51092, France

Location

CHU Rouen - Hospital Charles Nicolle

Rouen, Rouen, 76031, France

Location

CH Saint Etienne - Hospital Nord

Saint-Etienne, Saint Etienne, 42270, France

Location

CHU Tours - Hospital Trousseau

Chambray, Tours, 76031, France

Location

Complejo Hospitalario Santiago de Compostela

Santiago de Compostela, A coruña, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, Andalusia, 14004, Spain

Location

Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Location

Hospital Santa Creu i Sant Pau

Barcelona, Barcelona, 08025, Spain

Location

Hospital Doctor Negrin

Las Palmas de Gran Canarias, Canary Islands, 35010, Spain

Location

Hospital Universitario La Princesa

Madrid, Madrid, 28005, Spain

Location

Hospital Gregorio Marañón

Madrid, Madrid, 28007, Spain

Location

Hospital Ramón y Cajal

Madrid, Madrid, 28034, Spain

Location

Hospital Virgen del Rocío

Seville, Sevilla, 41013, Spain

Location

Hospital de Manises

Manises, Valencia, 46940, Spain

Location

Hospital Clínico de Valencia

Valencia, Valencia, 46010, Spain

Location

Hospital Lozano Blesa

Zaragoza, Zaragoza, Spain

Location

MeSH Terms

Conditions

Crohn Disease; Mucositis

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• VALLE GARCÍA, MD

  Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2012
• First Posted: March 26, 2012
• Study Start: October 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: May 4, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (12); ES (12); BE (6)