Efficacy, Safety and Pharmacokinetics of BI 655066/ABBV-066 (Risankizumab) in Patients With Active, Moderate-to-severe Crohn's Disease.

A Phase II, Multicenter, Randomized, Double-blind, Multiple Dose, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy, Pharmacokinetics, and Safety of BI 655066/ABBV-066 (Risankizumab), an IL-23 p19 Antagonist Monoclonal Antibody, in Patients With Moderately to Severely Active Crohn's Disease, Who Are naïve to, or Were Previously Treated With Anti-TNF Therapy

This study is a proof of concept, multi-center, randomized, double-blind, placebo-controlled, parallel-group phase 2 dose-ranging study of BI 655066/ABBV-066 (risankizumab), an IL-23 p19 antagonist monoclonal antibody, in patients with moderately to severely active Crohn's disease.

Inclusion criteria:

1. Men or women 18-75 years at the time of consent.

2. Diagnosis of Crohn's disease (CD) at least 3 months prior to screening.

3. Moderate to severe active CD, defined as Crohn's Disease Activity Index (CDAI) ≥ 220 and ≤ 450.

4. Presence of mucosal ulcers in at least one segment of the ileum or colon and a Crohn's Disease Endoscopic Index of Severity (CDEIS) score ≥ 7 (for patients with isolated ileitis, ≥4), as assessed by ileocolonoscopy and confirmed by central independent reviewer before randomization

5. Patients who are naive or experienced to 1 or more TNF antagonists (infliximab, adalimumab, or certolizumab pegol) at a dose approved for CD. TNF antagonist experienced patients may have stopped anti-TNF treatment due to primary or secondary non-responsiveness, intolerance or for other reasons.

6. Female patients:

   Women of childbearing potential (not surgically sterilized and between menarche and 1 year postmenopause), that, if sexually active agree to use one of the appropriate medically accepted methods of birth control in addition to the consistent and correct use of a condom from date of screening until 15 weeks after last administration of study medication. Medically accepted methods of contraception are: ethinyl estradiol containing contraceptives, diaphragm with spermicide substance, and intra-uterine-device, or

   1. Surgically sterilized female patients with documentation of prior hysterectomy, tubal ligation or complete bilateral oophorectomy, or
   2. Postmenopausal women with postmenopausal is defined as permanent cessation = 1 year of previously occurring menses, and
   3. Negative serum ß-Human Chorionic Gonadotrophin (ß-HCG) test at screening and urine pregnancy test prior to randomization.

   Male patients:

   1. Who are documented to be sterile, or
   2. Who consistently and correctly use effective method of contraception (i.e. condoms) during the study and 15 weeks after last administration of study medication.

7. Have the capacity to understand and sign an informed consent form.

8. Be able to adhere to the study visit schedule and other protocol requirements.

Exclusion criteria:

1. Have complications of CD such as strictures, stenoses, short gut syndrome, or any other manifestation that might require surgery, could preclude the use of the CDAI to assess response to therapy, or would possibly confound the evaluation of benefit from treatment with BI 655066.

2. Have any current or prior abscesses, unless they have been drained and treated at least 6 weeks prior to randomization and are not anticipated to require surgery. Patients with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses present.

3. Have had any kind of bowel resection or diversion within 6 months or any other intra-abdominal surgery within 3 months prior to screening. Patients with a current ileostomy or colostomy are excluded.

4. Have received treatment with:

   • Total parenteral nutrition (TPN) within 2 weeks of screening.
   • Any dose of ustekinumab (Stelara®).
   • Anti-TNF therapy ≤ 8 weeks prior to the first administration of study medication or any other biologic ≤ 8 weeks prior to the first administration of study drug or within 5 times the half-life of the biologic prior to the first administration of study agent, whichever is longer.
   • Natalizumab, efalizumab, or agents that deplete B or T cells (e.g., rituximab, alemtuzumab, or visilizumab) within 6 months of screening, or, if after receiving these agents, evidence is available at screening of persistent depletion of the targeted lymphocyte population.
   • Any investigational drug within the previous 4 weeks or 5 times the half-life of the investigational agent prior to the first administration of study agent, whichever is longer.
   • Regular daily use of opioids for medical reasons within previous 3 months prior to the first administration of study agent.
   • Rectal 5-aminosalicylic acid (5-ASA) compounds, parenteral or rectal corticosteroids must have been discontinued at least 4 weeks prior to visit 2.
   • Cannot adhere to the concomitant medication requirements specified in section 4.2.2.

5. Are pregnant, nursing, or planning pregnancy (both men and women) while enrolled in the study, or within 15 weeks after receiving the last dose of study medication.

6. Have used apheresis (e.g., Adacolumn apheresis) ≤ 2 weeks prior to screening.

7. Have received any live bacterial or viral vaccination ≤ 12 weeks prior to Day 1. Patients must agree not to receive a live virus or bacterial vaccination during the study or up to 12 months after the last administration of study drug.

8. Have had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening. Patient must agree not to receive a BCG vaccination during the study or up to 12 months after the last study drug administration.

9. Have signs or symptoms of infection, history of chronic or recurrent infection, have evidence of active herpes zoster infection ≤ 8 weeks of screening, have a stool culture or other examination positive for an enteric pathogen, have a history of latent or active granulomatous infection, infected with human immunodeficiency virus (HIV), hepatitis B (HepB) or hepatitis C (HepC) virus, established nonserious infections

10. Are not eligible according to tuberculosis (TB) screening criteria

11. Have severe, progressive or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, neurologic, cerebral or psychiatric disease or signs and symptoms.

12. Have a transplanted organ

13. Have known history of lymphoproliferative disease

14. Have any malignancy or history of malignancy

15. Have previously undergone allergy immunotherapy

16. Are unable or unwilling to undergo multiple venipunctures

17. Are known to have substance abuse

18. Are currently or intending to participate in any other study

19. Have screening laboratory test results within the protocol stated parameters

20. Have a known hypersensitivity to study drug

21. Have evidence of current or previous clinically significant disease, medical condition other than CD, finding of the medical examination or lab value.