Biomarkers in diagnosis & treatment of patients with Crohn’s disease treated with immunosuppressants

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2011-003966-34-BE
• Date of registration: 11/10/2011
• Prospective Registration: Yes
• Primary sponsor: Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU)
• Public title: Biomarkers in diagnosis & treatment of patients with Crohn’s disease treated with immunosuppressants
• Scientific title: The ADACAL Study: 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: 06/12/2011
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-003966-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Spain

Contacts

• Name: President GETECCU
• Affiliation: Grupo Español Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU)

• Name: President GETECCU
• Affiliation: Grupo Español Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU)

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 = 250µg/g and/or hsCRP = 5mg/L.
• Significant lesions seen during colonoscopy, as defined by CDEIS.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 180

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:
o Live vaccines.
o 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.
o Oral corticosteroids (eg., Prednisone, budesonide) should be discontinued for 3 months before study inclusion.
o Antibiotics for CD. Only antibiotics used to treat a concurrent infection are allowed.
o 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.
o Monoclonal antibodies or anti-TNF drugs.
o 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:
o Aspartate transaminase (AST) or alanine transaminase (ALT) > 2 x the upper limit of the reference range;
o Total bilirubin = 3 mg/dL (51 µmol/L);
o 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

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Crohn's disease (CD) is an inflammatory disease of the intestines that primarily causes abdominal pain, diarrhea, vomiting, or weight loss.

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Trade Name: Humira
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 40-160
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: - To assess the effect of an individualized treatment according to a new calprotectin and hsCRP based diagnostic-therapeutic strategy on mucosal healing, quality of life, work productivity, number of hospital admissions, and surgical interventions.
- To determine the value of calprotectin and hsCRP in predicting therapeutic failure, and mucosal healing.
- To correlate hsCRP with calprotectin.

Timepoint(s) of evaluation of this end point: Data will be evaluated in combination after last patient last visit.

Main Objective: To assess the effect of individualized treatment according to a new calprotectin/ high-sensitivity C-reactive protein (hsCRP)-based diagnostic-therapeutic strategy on the mid-term outcome in Crohn’s Disease (CD) patients.

Primary end point(s): The primary efficacy endpoint is the rate of therapeutic failure up to week 48.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Data will be evaluated in combination after last patient last visit.

Secondary end point(s): • The rate of therapeutic failure up to week 24.
• Change in CDEIS from baseline to week 48.
• The rate of mucosal healing (CDEIS=0) at week 48.
• The rate of CDEIS remission (CDEIS<=3) 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.
• Change in CDAI 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.
• Change in the scores based on WPAI from baseline to week 12, 24, 36 and 48.
• Area Under the Curve (AUC) over 48 weeks for CDAI.
• The number of surgical interventions related to CD up to 24 and 48 weeks.
• The rate of hospital admissions related to the disease, to the treatment side effects or other causes up to weeks 24 or 48.
• Calprotectin levels based on PhiCal tests;
• hsCRP levels

Secondary ID(s)

A12-771

Source(s) of Monetary Support

Abbott Laboratories