An Open-Label, Multicenter, Efficacy and Safety Study to Evaluate Two Treatment Algorithms in Subjects with Moderate to Severe Crohn's Disease - CALM

Phase 1

Conditions: Crohn's disease
MedDRA version: 12.1 Level: LLT Classification code 10011401 Term: Crohn's disease

Registration Number: EUCTR2010-020137-10-FR

Lead Sponsor: Abbott GmbH & Co. KG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 252

Inclusion Criteria

1. Males and females = 18 and = 75 years of age at the Baseline visit.
2. Diagnosis of colonic or ileocolonic CD confirmed using imaging technology or endoscopy not more than 4 years prior to Baseline.
3. CDAI score of = 220 and = 450 at the Baseline visit.
4. Crohn's disease Endoscopic Index of Severity (CDEIS) > 6 in at least one non ileal segment, with presence of ulcers, AND total CDEIS > 8, at the Screening visit.
5. hs-CRP = 0.5 mg/dL at the Screening visit.
6. Fecal Calprotectin = 250 µg/g at the Screening visit.
7. If female, subject is either not of child bearing potential, defined as post menopausal for at least 1 year, surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or is of childbearing potential and practicing one of the following methods of birth control during the study and for 150 days after the last dose:
• Condoms, sponge and foam, jellies with diaphragm or intrauterine device (IUD). IUDs may fail during azathioprine treatment. Alternative or additional contraceptive measures are advised, if azathioprine is initiated.
• Oral or parenteral contraceptives for 3 months prior to study drug administration.
• A vasectomized partner.
8. Male subjects must agree to use an acceptable form of birth control, listed above at the start of azathioprine administration and for 90 days after last dose of azathioprine. Males should also commit to inform his partner(s) about it and to report any pregnancy to the investigator.
9. If female, subject is not breast-feeding throughout the study and for 150 days after last dose.
10. Subjects or his/her legal representative have voluntarily signed and dated an informed consent approved by and compliant with the requirements of this study protocol which has been approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
11. Adequate cardiac, renal and hepatic function as determined by the Principal Investigator and demonstrated by Screening laboratory evaluations, questionnaires and physical examination results that do not indicate an abnormal clinical condition which would place the subject at undue risk and thus preclude subject participation in the study.
12. Subjects must be able to self-inject and orally administer study medication or have a designee or Healthcare Professional who can assist.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Previous or current biologic use for Crohn's disease or participation in a biologic study.
2. Previous or current use of immunomodulators (e.g., methotrexate, azathioprine, 6-mercaptopurine) for Crohn's disease or participation in an immunomodulator study.
3. Corticosteroid use for Crohn's disease within 6 months of Screening.
4. Greater than one previous course of corticosteroid.
5. Corticosteroid use for Crohn's disease in the previous 2 years before Screening for > 6 months.
6. Subjects not on stable doses of aminosalicylates, or CD-related antibiotics (fluoroquinolones such as ciprofloxacin, nitroimidazole derivatives such as metronidazole, and rifaximin) for at least 4 weeks prior to Baseline. Subject must consent to remain on stable doses throughout the entire trial.
7. Subjects on topical therapy for Crohn's disease.
8. Deficient or low Thiopurine methyltransferase (TPMT) enzyme activity (= 34 nmol/g Hb/hour).
9. Montreal Classification B3 or Montreal classification B2 with symptoms of obstruction.
10. Stricturing on ileocolonoscopy at Screening regardless of symptoms.
11. Greater than one major surgery for Crohn's disease in the medical history, or planned surgery for Crohn's disease.
12. History of malignancy (including lymphoma and leukemia) other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix.
13. History of listeriosis, histoplasmosis, human immunodeficiency virus (HIV), chronic or active hepatitis B, an immunodeficiency syndrome, central nervous system (CNS) demyelinating disease (including myeletis), neurologic symptoms suggestive of demyelinating disease, chronic recurring infection, active TB (receiving treatment or not receiving treatment), severe infections such as sepsis and opportunistic infections. PPD test positive at Screening = 5 mm.
14. Subjects with a current diagnosis of ulcerative colitis or indeterminate colitis as determined by the Investigator and Abbott Medical Monitor.
15. Subjects with an ostomy, or ileoanal pouch (subject with previous ileo-rectal anastomosis are not excluded), draining fistula, abscess.
16. Subjects who have short bowel syndrome as determined by the Investigator.
17. Subjects who are currently receiving total parenteral nutrition (TPN).
18. Subjects who are currently receiving enteral nutrition via a tube for complete nutrition.
19. Females who are pregnant, considering becoming pregnant or will not discontinue breast feeding.
20. Subjects who has received any investigational chemical or biological agent in the past 30 days or 5 half-lives prior to Baseline (whichever is longer).
21. Subjects who have had systemic antibiotic, antiviral or antifungal treatment(s) within 3 weeks prior to Baseline for all non–Crohn's-related infections.
22. Subjects with a history of clinically significant drug or alcohol abuse in the last year.
23. 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 failu

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> Main Objective: To demonstrate that tight control of disease activity using stringent<br> criteria based on CDAI, hs-CRP, fecal Calprotectin, and corticosteroid use improves the rate of mucosal healing at Week 56, as compared to management using less stringent criteria based on CDAI and corticosteroid use.<br> ;Secondary Objective: To assess the pharmacokinetics (PK) of adalimumab following subcutaneous administration.;<br> Primary end point(s): The primary efficacy variable is the proportion of subjects with mucosal healing<br> (CDEIS < 4) and no deep ulcerations on ileocolonoscopy (absence of all deep ulcerations in all segments explored in CDEIS) at Week 56.<br>

Secondary Outcome Measures

Name	Time	Method

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