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

Phase 3

Completed

• Conditions: Crohn's Disease; 10017969

• Registration Number: NL-OMON39794
• Lead Sponsor: AbbVie

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 2017-12-15
• Last Update Posted: 6 May 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 16

Inclusion Criteria

1. Males and females >= 18 and <= 75 years of age at the Baseline visit.
2. Diagnosis of ileal, colonic (including rectal), or ileocolonic CD confirmed using imaging technology or endoscopy not more than 6 years prior to Baseline.
3. Moderate to severe Crohn's disease defined as CDAI score of >= 220 and <= 450 at the Baseline visit in subjects not receiving prednisone or equivalent at Baseline. CDAI score of >= 200 and <= 450 at the Baseline visit if the subject is receiving prednisone <= 20 mg or equivalent for >= 7 days before Baseline. CDAI score of > 150 and <= 450 at the Baseline visit if the subject is receiving prednisone > 20 mg or equivalent for >= 7 days before Baseline.
4. Sum of deep ulcerations, superficial ulcerations, surface involved by disease, surface involved by ulceration CDEIS subscores in at least one ileal or non-ileal segment > 6, with presence of ulcers, AND total CDEIS > 6, on Screening endoscopy.
5. Inclusion Criterion deleted in Amendment 2.
6. hs-CRP >= 5 mg/L (>= 47.6 nmol/L) at the Screening visit and/or 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.
13. Subject has a negative TB Screening Assessment [(including a PPD test < 5 mm and/or negative QuantiFERON-TB Gold test or equivalent and negative CXR (PA and lateral view)] at Screening.

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, JAK inhibitor, alpha-integrin inhibitors) for Crohn's disease or participation in a Crohn's disease study with immunomodulator(s). Current use of immunomodulators for non-Crohn's disease at Baseline.
3. Exclusion Criterion deleted in Amendment 3.
4. Greater than two previous courses of corticosteroid (systemic corticosteroid) or budesonide) for Crohn's Disease. A course is defined as 1) total duration for burst and taper >= 4 weeks and 2) prednisone or equivalent >= 40 mg (or budesonide >= 9 mg) for at least 2 weeks.
5. Currently receiving systemic corticosteroid or budesonide for Crohn's disease for > 3 months before Screening.
6. Exclusion Criterion deleted in Amendment 2.
7. Exclusion Criterion deleted in Amendment 2.
8. Deficient Thiopurine methyltransferase (TPMT) enzyme activity (<= 20 mU/L) OR intermediate TPMT enzyme activity (> 20 and <= 67 mU/L) and subject does not consent to undergo a weekly laboratory surveillance for 4 weeks or longer according to local guidelines if escalated to Therapeutic Option 4 (adalimumab and azathioprine).
9. Montreal Classification B3 or Montreal classification B2 with symptoms of obstruction. The assessment of imaging data with respect to Montreal classification will be discussed with the Medical Monitor.
10. Non passable stricture or passable stricture, even if dilatated during screening ileocolonoscopy with pre-stenotic dilatation on ileocolonoscopy at Screening regardless of symptoms.
11. Greater than one major surgery for Crohn's disease in the medical history, or planned or recent (< 6 months of Screening) 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), 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.
14. Subjects with a current diagnosis of ulcerative colitis or indeterminate colitis as determined by the Investigator and AbbVie 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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary efficacy variable is the proportions of subjects with mucosal<br /><br>healing (CDEIS < 4) and no deep ulcerations on ileo-colonoscopy (absence of all<br /><br>deep ulcerations in all segments explored in CDEIS) 48 weeks after<br /><br>randomisation. The ileo-colonoscopies will be evaluated by the site. The<br /><br>secondary efficacy variables are described at page 103-106 section 5.3.3.2<br /><br>protocol amendment 4 dd 21 March 2013.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The secondary objective of this study is to assess the pharmacokinetics (PK) of<br /><br>adalimumab following subcutaneous administration</p><br>