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

• Register: ClinicalTrials.gov
• Last refreshed on: 17 May 2016
• Main ID: NCT01562951
• Date of registration: 13/03/2012
• Prospective Registration: Yes
• Primary sponsor: Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa
• Public title: Assessment of Mucosal Activity to Improve the Prognosis of Patients With Crohn's Disease Treated With Immunosuppressants ADACAL
• Scientific title: cAlprotectin and hsCRP as Markers of a New Diagnostic-therapeutic strAtegy That Assesses muCosal Activity to individuaLize Treatment and Improve the Prognosis of Patients With Crohn's Disease Treated With Immunosuppressants
• Date of first enrolment: October 2012
• Target sample size: 15
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT01562951
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
• Phase: Phase 3

Countries of recruitment

Belgium, France, Spain

Contacts

• Name: VALLE GARCÍA, MD
• Affiliation: Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 75 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Mucosal Inflammation

Crohn's Disease

Intervention(s)

Drug: ADALIMUMAB

Drug: Placebo

Primary Outcome(s)

The primary efficacy endpoint is the rate of therapeutic failure up to week 48 [Time Frame: Every 12 weeks up to Week 48]

Secondary Outcome(s)

The rate of CDEIS remission (CDEIS<=3) at week 48 [Time Frame: at week 48]

The rate of hospital admissions related to the disease, to the treatment side effects or other causes up to weeks 24 or 48 [Time Frame: up to weeks 24 or 48]

The rate of mucosal healing (CDEIS=0) at week 48 [Time Frame: at week 48]

Change in CDEIS from baseline to week 48 [Time Frame: up to 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 [Time Frame: from baseline up to week 48]

The number of surgical interventions related to CD up to 24 and 48 weeks [Time Frame: up to 24 and 48 weeks]

The change in calprotectin and hsCRP from baseline to week 12, 24, 36, and 48 [Time Frame: from baseline to week 12, 24, 36, and 48]

Change in CDAI from baseline to week 12, 24, 36 and 48 [Time Frame: from baseline to week 12, 24, 36 and 48]

Change in the global score based on IBDQ from baseline to week 12, 24, 36, and 48. [Time Frame: from baseline to week 12, 24, 36, and 48.]

The correlation between calprotectin, hsCRP and CDAI at any time points during the study. [Time Frame: 48 weeks]

The rate of serious AEs between the two strategies up to 24 and 48 weeks [Time Frame: up to 24 and 48 weeks]

The rate of serious AEs requiring the cessation of the ongoing treatment between the two strategies up to 24 and 48 weeks. [Time Frame: up to 24 and 48 weeks]

Change in the scores based on WPAI from baseline to week 12, 24, 36 and 48 [Time Frame: from baseline to week 12, 24, 36 and 48]

Area Under the Curve (AUC) over 48 weeks for CDAI [Time Frame: 48 weeks]

The accuracy of calprotectin/hsCRP to predict therapeutic failure 12 weeks in advance [Time Frame: 12 weeks]

The rate of therapeutic failure (see the definition of primary endpoint) up to week 24 [Time Frame: up to week 24]

The correlation between calprotectin/hsCRP and CDEIS or mucosal healing at Baseline and Week 48. [Time Frame: at Baseline and Week 48.]

Secondary ID(s)

A12-771

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

TFS Trial Form Support

Abbott