Ensayos clínicos

Inclusion Criteria:

• Male or female aged ≥ 18 to ≤ 80 years, or minimum age of adult consent according to local regulations, at the Baseline visit. Where locally permissible, subjects 16 to < 18 years of age who meet the definition of Tanner stage 5 for development at the Baseline Visit (sites will be notified when adolescents may enroll).
• Confirmed diagnosis of CD for at least 3 months prior to Baseline. Appropriate documentation of biopsy results consistent with the diagnosis of CD, in the assessment of the Investigator, must be available.
• Crohn's disease activity index (CDAI) score 220 – 450 at Baseline.
• Endoscopic evidence of mucosal inflammation as documented by the SES-CD of ≥ 3. All eligible scores exclude the presence of narrowing component and are confirmed by a central reader. (Once cap of no more than 10% is reached, enrollment criterion will be an SES-CD of ≥ 6 for ileocolonic or colonic disease or SES-CD of ≥ 4 for isolated ileal disease).
• Average daily SF ≥ 4 and/or average daily AP score ≥ 2 at Baseline.
• Demonstrated intolerance or inadequate response to one or more of the following biologic agents as defined below: infliximab, adalimumab, certolizumab pegol, natalizumab, vedolizumab and/or ustekinumab:
  • Demonstration of intolerance requires no minimum dose or duration of use;
  • Inadequate response to biologic agents defined as signs and symptoms of persistently (in the opinion of the Investigator) active disease despite a history of one or more of the following:
    • At least one 6-week induction regimen of infliximab (≥5 mg/kg IV at Weeks 0, 2, and 6);
    • At least one 4-week induction regimen of adalimumab (one 160 mg SC dose at Week 0, followed by one 80 mg SC dose at Week 2 [or one 80 mg SC dose at Week 0, followed by one 40 mg SC dose at Week 2, in countries where this dosing regimen is approved]);
    • At least one 4-week induction regimen of certolizumab pegol (400 mg SC at Weeks 0, 2, and 4);
    • At least one 6-week induction regimen of vedolizumab (300 mg IV at Weeks 0, 2, and 6);
    • At least one 12-week induction regimen of natalizumab (300 mg IV every 4 weeks);
    • At least one 8-week induction regimen of ustekinumab [260 mg (≤55 kg) or 390 mg (> 55 to ≤85 kg) or 520 mg (> 85 kg) IV, followed by 90 mg SC at Week 8] (Once cap of no more than 20% ustekinumab exposed subjects is reached, subjects with prior ustekinumab exposure will not be allowed to enroll).
  • Recurrence of symptoms during scheduled maintenance dosing following prior clinical benefit of the above biologic agents.
  • Note: Subjects who discontinued biologic agents for reasons other than inadequate response as defined above or intolerance (e.g., change of insurance) are not eligible to enroll.
• If female, subject must meet the criteria as stated in Section 5.2.4 of this protocol Contraception Recommendations. Females of childbearing potential must have a negative serum pregnancy test result during Screening, and a negative urine pregnancy at  Baseline. Females of non-childbearing potential (either postmenopausal or permanently surgically sterile as defined in Section 5.2.4) during Screening do not require pregnancy testing at Baseline.
  • Note: Subjects with borderline serum pregnancy test at Screening must have a serum pregnancy test ≥ 3 days later to document continued lack of a positive result.
• Subject must be able and willing to give written informed consent and to comply with the requirements of this study protocol.

Exclusion Criteria:

• Subject with a current diagnosis of ulcerative colitis or indeterminate colitis.

Concomitant Medications and Treatments

• Subject on CD-related antibiotics who has not been on stable doses for greater than, or discontinued within, 14 days prior to Baseline.
• Subject on oral aminosalicylates who has not been on stable doses for greater than, or discontinued within, at least 14 days prior to Baseline.
• Subject taking oral corticosteroids:
  •  Budesonide > 9 mg/day;
  •  Beclomethasone > 5 mg/day;
  •  Prednisone or equivalent > 20 mg/day;
  •  Or has not been on the current course for ≥ 14 days prior to Baseline and on a stable dose for ≥ 7 days prior to Baseline.
• Subject on immunomodulators (AZA, 6-MP, MTX) who:
  • Has not been on the current course for ≥ 42 days prior to Baseline;
  • Has not been on a stable dose for ≥ 35 days prior to Baseline.

Medications and Treatments During the Screening Period

• Subject who received IV anti-infectives within 35 days prior to Baseline visit or oral/intramuscular anti-infectives (non-CD-related) within 14 days prior to the Baseline visit.
• Subject who received exclusive enteral nutrition or any parenteral nutrition within 35 days prior to Baseline.
• Subject who received any live bacterial or viral vaccination within 30 days prior to Screening or during the Screening period.
• Subject who received cyclosporine, tacrolimus, or mycophenolate mofetil within 35 days prior to Baseline.
• Subject who received fecal microbial transplantation within 35 days prior to Baseline.

Prior Medications and Treatments

• Subject who received any approved biologic agent (e.g., infliximab, adalimumab, certolizumab, natalizumab, vedolizumab) within 8 weeks prior to Baseline, or any investigational biologic or other agent or procedure within 35 days or 5 half-lives prior to Baseline, whichever is longer.
• Subject with prior exposure to p40 inhibitors (e.g., ustekinumab [Stelara]), p19 inhibitors (e.g., risankizumab).
• Subject has been taking combination of two or more of the following oral budesonide, or oral beclomethasone and/or oral prednisone (or equivalent) simultaneously, with the exception of inhalers, within 14 days prior to Screening or during the Screening period.
• Subject who received IV corticosteroids within 14 days prior to Screening or during the Screening period.
• Subject who received therapeutic enema or suppository, other than required for endoscopy, within 14 days prior to endoscopy used for Screening or during the Screening period.
• Subject who received apheresis (e.g., Adacolumn apheresis) ≤ 60 days prior to Screening or during the Screening period.
• Subject who has concomitant cannabis use either recreational or for medical reasons within 14 days of Baseline or any history of clinically significant drug, or alcohol abuse in the last 12 months.

CD Related

• Subject with currently known complications of CD such as:
  • abscess (abdominal or perianal);
  • symptomatic bowel strictures;
  • > 2 missing segments of the following 5 segments: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum
  • fulminant colitis;
  • toxic megacolon;
  • or any other manifestation that might require surgery while enrolled in the study.
• Subject with ostomy or ileoanal pouch.
• Subject diagnosed with short gut or short bowel syndrome.
• Subject with surgical bowel resection within the past 3 months prior to Baseline, or a history of ≥ 3 bowel resections.
• Safety
• Subject who has a known hypersensitivity to risankizumab or the excipients of any of the study drugs or the ingredients of Chinese hamster ovary (CHO).
• Subjects with the following chronic or active infections:
  • Active, chronic, or recurrent infection that based on the Investigator's clinical assessment makes the subject unsuitable candidate for the study;
  • Infection with C. difficile toxin or other intestinal pathogen during Screening;
  • Are infected with human immunodeficiency virus (HIV);
  • QuantiFERON®-TB test or Purified Protein Derivative (PPD) skin test, or both, according to local guidelines, will be performed during Screening. QuantiFERON®-TB test is preferred for subjects who received BCG vaccination or were exposed to other Mycobacteria species.  Subjects with a positive test result (or indeterminate results that have been repeated) may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the subject has no evidence of active tuberculosis. Subjects with a history of active TB who have documented completion of a full course of anti-TB therapy may be allowed to enter the study after consultation with the AbbVie TA MD. If latent TB is established, TB prophylaxis/treatment should be initiated and maintained according to local country guidelines;
  • Have active hepatitis B or hepatitis C defined as: 
    • HBV: hepatitis B surface antigen (HBs Ag) positive (+), or detected sensitivity on the HBV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) qualitative test for hepatitis B core antibody (HBc Ab) positive subjects;
    • HCV: HCV ribonucleic acid (RNA) detectable in any subject with positive anti-HCV antibody (HCV Ab).
• Subject with a previous history of dysplasia of the gastrointestinal tract or found to have dysplasia, other than completely removed low-grade dysplastic lesions, in any biopsy performed during the Screening endoscopy.
• Subject with a known history of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly.
• Subject with current or previous history of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix.
• Subject who has severe, progressive, or uncontrolled renal, hepatic, hematological, endocrine, disorder or symptoms thereof.
• Female subjects who is pregnant, breastfeeding, or is considering becoming pregnant during the study or for approximately 140 days after the last dose of study drug.
• Subject who has any condition, including any physical, psychological, or psychiatric condition, which in the opinion of the Investigator, would compromise the safety of the subject or the quality of the data and renders the subject an unsuitable candidate for the study.
• Screening laboratory and other analyses show any of the following abnormal results:  
  • Aspartate transaminase (AST), alanine transaminase (ALT) > 2 × upper limit of the reference range;
  • White blood cell (WBC) count < 3.0 × 109/L;
  • Total bilirubin ≥2 mg/dL; except for subjects with isolated elevation of indirect bilirubin relating to Gilbert syndrome;
  • Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 30 ml/min/1.73 m2;
  • Hemoglobin < 8 g/dL;
  • Platelets < 100,000/μL;
  • Positive serum pregnancy test at the Screening visit or positive urine pregnancy test at the Baseline visit.