Efficacy and Safety of Two Treatment Models in Subjects With Moderate to Severe Crohn's Disease (CALM)

• Assess Pharmacokinetics (PK) of adalimumab following subcutaneous injection; a PK blood draw at protocol defined time points. Serum concentrations of adalimumab will be determined using a validated Ligand binding assay (LBA) method. [ Time Frame: 48 weeks after Randomization ] [ Designated as safety issue: No ]
  Subjects will have a PK blood draw at protocol defined time points. Serum concentrations of adalimumab will be determined using a validated Ligand binding assay (LBA) method.
• Safety will be assessed through clinical laboratory tests, vital signs, physical exams and adverse event assessments. [ Time Frame: Starting the day Informed Consent is signed through the study to Final/Early Termination. In addition, 70 days after the last visit, the site will contact the subject to collect any safety data. ] [ Designated as safety issue: Yes ]
  Safety will be assessed through clinical laboratory tests, vital signs, physical exams and adverse event assessments.

• Assess Pharmacokinetics (PK) of adalimumab following subcutaneous injection; a PK blood draw at protocol defined time points. Serum concentrations of adalimumab will be determined using a validated enzyme-linked immunosorbent assay (ELISA) method. [ Time Frame: 56 weeks ] [ Designated as safety issue: No ]
  Subjects will have a PK blood draw at protocol defined time points. Serum concentrations of adalimumab will be determined using a validated enzyme-linked immunosorbent assay (ELISA) method.
• Safety will be assessed through clinical laboratory tests, vital signs, physical exams and adverse event assessments. [ Time Frame: Starting the day Informed Consent is signed through the study to week 56 or Early Termination. In addition, 70 days after the last visit, the site will contact the subject to collect any safety data. ] [ Designated as safety issue: Yes ]
  Safety will be assessed through clinical laboratory tests, vital signs, physical exams and adverse event assessments.

Efficacy and Safety of two treatment models in subjects with moderate to severe Crohn's Disease.

• Biological: adalimumab
  Subject will be assigned to this intervention during the study upon Success Criteria evaluations.
  Other Names:

  • ABT-D2E7
  • Humira
• Drug: prednisone
  All subjects will start this intervention upon enrollment into the study except those that Early Randomize and meet protocol specific criteria. Depending on the evaluation criteria subjects may continue this therapy or stop it during the study.
• Drug: azathioprine
  Subjects will start this therapy after moving through all other therapeutic options. This will be used in conjunction with adalimumab and once assigned to this intervention, the subject will continue taking it until they complete the study or discontinue.

• Active Comparator: Tight Control
  The Tight Control arm manages disease activity using more stringent criteria than the Clinically Driven arm.
  Interventions:

  • Biological: adalimumab
  • Drug: prednisone
  • Drug: azathioprine
• Active Comparator: Clinically Driven
  The Clinically Driven arm manages disease activity using less stringent criteria.
  Interventions:

  • Biological: adalimumab
  • Drug: prednisone
  • Drug: azathioprine

Inclusion Criteria:

• Males and females greater than or equal to 18 and less than or equal to 75 years of age at the Baseline visit.
• Diagnosis of ileal, colonic (including rectal), or ileocolonic CD confirmed using imaging technology or endoscopy not more than 6 years prior to Baseline.
• CDAI score of greater than or equal to 220 and less than or equal to 450 at the Baseline visit in subjects not receiving prednisone or equivalent at Baseline. CDAI score of greater than or equal to 200 and less than or equal to 450 at the Baseline visit if the subject is receiving prednisone less than or equal to 20 mg or equivalent for greater than or equal to 7 days before Baseline. CDAI score of greater than 150 and less than or equal to 450 at the Baseline visit if the subject is receiving prednisone greater than 20 mg or equivalent for greater than or equal to 7 days before Baseline
• 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).
• 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.
• Subjects must be able to self-inject and orally administer study medication or have a designee or Healthcare Professional who can assist

Exclusion Criteria:

• Previous or current biologic use for Crohn's disease or participation in a biologic study
• Previous or current use of immunomodulators (e.g., methotrexate, azathioprine, 6-mercaptopurine, JAK inhibitor, alpha-integrin) 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.
• Exclusion Criterion deleted in Amendment 3-"Receiving systemic corticosteroid for Crohn's disease at a dose of prednisone equivalent greater than to 20 mg per day or budesonide greater than 6 mg per day 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 (NYHA class III or IV), recent cerebrovascular accident and any other condition which, in the opinion of the Investigator or the sponsor, would put the subject at risk by participation in the protocol
• Subjects with positive C. difficile stool assay at Screening.