Ensayos clínicos

Inclusion Criteria:

• Males or females ≥ 18 and ≤ 80 years of age, or minimum age of adult consent according to local regulations at the Baseline Visit.
• In addition, for Sub-Study 2 only: Where locally permissible, subjects 16 to < 18 years of age who meet the definition of Tanner Stage 5 for development at the Baseline Visit.
• Confirmed diagnosis of UC for at least 3 months prior to Baseline. Appropriate documentation of biopsy results consistent with the diagnosis of UC or in the assessment of the Investigator, must be available.
• Active UC with an Adapted Mayo score of 5 to 9 points and endoscopic subscore of 2 to 3 (confirmed by central review).
• Demonstrated intolerance or inadequate response to one or more of the following categories of drugs: aminosalicylates, oral locally acting steroids, systemic steroids (prednisone or equivalent), immunomodulators, and/or biologic therapies or tofacitinib:
  • Demonstration of intolerance requires no minimum dose or duration of use;
  • Inadequate response is defined as outlined below:
    • Oral aminosalicylates (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide):
  • Signs and symptoms of persistently active disease, in the opinion of the Investigator, during a current or prior course of at least 4 weeks of treatment with 2.4 g/day mesalamine (2 g/day if controlled release), 4 g/day sulfasalazine, 1 g/day olsalazine, or 6.75 g/day balsalazide;
  • Oral locally acting steroids (e.g., budesonide, beclomethasone);
  • Signs and symptoms of persistently active disease, in the opinion of the Investigator, during or after a course of at least 4 weeks of treatment with 9 mg/day budesonide or 5 mg/day beclomethasone; OR
  • Inability to taper oral budesonide to at or below 6 mg/day without recurrent active disease;
  • IV or Oral systemic steroids (prednisone or equivalent);
  • Signs and symptoms of persistently active disease, in the opinion of the Investigator, during or after tapering of at least one regimen consisting of a dose equivalent to prednisone ≥ 40 mg/day orally for 3 weeks or intravenously for 1 week; OR 
  • Inability to taper oral systemic steroids to at or below a dose equivalent to prednisone 10 mg/day without recurrent active disease.
• Signs and symptoms of persistently active disease, in the opinion of the Investigator, during a current or prior course of at least 90 days of treatment with one or more of the following:
  • AZA: ≥ 2.0 mg/kg/day rounded to the nearest available tablet or half tablet formulation (≥ 1 mg/kg/day for subjects in Japan, Korea, Taiwan, Singapore, or China) (or a documented 6-TGN level of ≥ 230 pmol/8 × 108 RBC);
  • 6-MP: ≥ 1 mg/kg/day rounded to the nearest available tablet or half tablet formulation (≥ 0.6 mg/kg/day for subjects in Japan, Korea, Taiwan, Singapore, or China) (or a 6-TGN level of ≥ 230 pmol/8 × 108 RBC);
  • MTX: ≥ 15 mg/week subcutaneous (SC) or intramuscular (IM);
  • Note: Oral MTX use is allowed during the study; however, prior or current use of oral MTX is not sufficient for inclusion into the study:
    • Tacrolimus: (for Japan, Taiwan and other countries in Asia with local treatment guidelines that include tacrolimus) documented trough level 5 - 10 ng/mL.
  • Biologic Therapies and tofacitinib for UC: Signs and symptoms of persistently active disease despite a history of one or more of the following:
    • At least one 6-week induction regimen of infliximab (≥ 5 mg/kg intravenous [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 golimumab (200 mg SC at Week 0 and 100 mg SC at Week 2); 
    • At least one 6-week induction regimen of vedolizumab (300 mg IV at Weeks 0, 2, and 6);
    • At least one 8-week induction regimen of tofacitinib (10 mg PO twice daily).
  • Recurrence of symptoms during scheduled maintenance dosing following prior clinical benefit of the above biologics.
  • Note: Subjects who discontinued biologics or tofacitinib for reasons other than inadequate response as defined above or intolerance (e.g., change of insurance) must meet the criteria for intolerance or inadequate response to aminosalicylates, oral locally acting steroids, systemic steroids (prednisone or equivalent), and/or immunomodulators as defined above.
• If female, subject must meet the criteria as stated in 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) during Screening do not require pregnancy testing at Baseline.
• Subject must be able and willing to give written informed consent and to comply with the requirements of this study protocol. In Japan, if the subject is < 20 years old, a subject's parent or legal guardian must be willing to give written informed consent.

Exclusion Criteria:

• Subject with a current diagnosis of Crohn's disease (CD), IBD-unclassified (IBD-U) or a history of radiation colitis or ischemic colitis.
• Subject on oral UC-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 course for ≥ 42 days prior to Baseline; and
  • Has not been on a stable dose for ≥ 35 days prior to Baseline.
• Subject who received IV anti-infectives within 35 days prior to Baseline visit or oral anti-infectives (non-UC-related) within 14 days prior to the Baseline visit. This does not apply to TB prophylaxis.
• Subject who received any parenteral nutrition within 35 days prior to Baseline.
• Subject who received any live bacterial or viral vaccination within 35 days (8 weeks for Japan) prior to Baseline.
• 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.
• Subject who received any:
  • approved biologic agent (e.g., infliximab, adalimumab, golimumab, vedolizumab) within 8 weeks prior to Baseline or tofacitinib within 35 days prior to Baseline.
• Subject with prior exposure to p40 inhibitors (e.g., ustekinumab [Stelara]) or p19 inhibitors (e.g., risankizumab).
• Subject has been taking combination of two or more of the following oral budesonide, 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/intramuscular corticosteroids within 14 days prior to Screening or during the Screening period. 
• Subject who received therapeutic enema or suppository (i.e., rectal aminosalicylates/corticosteroids), other than required for endoscopy, within 14 days prior to 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 prior to Baseline or any history of clinically significant drug, or alcohol abuse in the last 12 months.
• Extent of inflammatory disease limited to the rectum as assessed by screening endoscopy.
• Subject with currently known complications of UC such as:
  • fulminant colitis;
  • toxic megacolon;
  • previous colectomy (total or subtotal);
  • or any other manifestation that might require surgery while enrolled in the study.
• Subject with ostomy or ileoanal pouch.
• 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 as identified during Screening;
  • Known infection with an intestinal pathogen;
  • 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: o 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; o HCV: HCV ribonucleic acid (RNA) detectable in any subject with 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 or 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 × 10^9 /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 m^2; 
  • 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.
• No known active COVID-19 infection. If a subject has signs/symptoms suggestive of COVID-19, they should undergo molecular (i.e., PCR) testing to rule out SARS-CoV-2 infection. 
• Subjects who do not meet COVID-19 eligibility criteria must be screen failed and may only rescreen after they meet the following criteria:
• Symptomatic subjects: At least 14 days have passed since recovery, defined as resolution of fever without use of antipyretics and improvement in symptoms. 
• Asymptomatic subjects: At least 14 days have passed since the first positive molecular (i.e., PCR) test result. Laboratory values can be re-tested once during the screening period. If the re-tested lab value(s) remain(s) exclusionary, the subject will be considered a screen failure. Redrawing samples if previous samples were unable to be analyzed would not count as a retest since previous result was never obtained.