A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Participants With Moderately to Severely Active Ulcerative Colitis

AbbVie522 enrolled

Overview

The objective of this study is to evaluate the efficacy and safety of upadacitinib compared to placebo in inducing clinical remission (per Adapted Mayo score) in participants with moderately to severely active ulcerative colitis (UC).

Study M14-675 consists of 2 parts, Part 1 and Part 2. Part 1 is a randomized, double-blind, placebo-controlled 8-week induction period. Part 2 is an open-label, 8-week extended treatment period for participants who did not achieve clinical response at Week 8 in Part 1. Eligible participants are randomized in a 2:1 ratio to one of the two treatment groups (upadacitinib 45 mg or matching placebo) for 8 weeks. The randomization is stratified by biologic inadequate responder (bio-IR) status (bio-IR vs non-bio-IR), corticosteroid use (yes or no), and Adapted Mayo score (≤ 7 or \> 7) at Baseline. Within bio-IR, the randomization is further stratified by number of prior biologic treatments (≤ 1 or \> 1). Within non-bio-IR, the randomization is further stratified by previous biologic use (yes or no). Participants who achieve clinical response defined by Adapted Mayo Score at Week 8 or Week 16 and do not meet any study discontinuation criteria are eligible to enroll into Study M14-234 Substudy 3 (NCT02819635; 52-week maintenance study) or Study M14-533 Cohort 1 (NCT03006068; long-term follow-up study).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

522

Conditions

Ulcerative Colitis (UC)

Interventions

PlaceboDRUG

Tablet for oral administration

UpadacitinibDRUG

Tablet for oral administration

Eligibility

Sex: ALLMin age: 16 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: \- Male or female participants ≥ 16 and ≤ 75 years of age at Baseline Note: Adolescent participants at the age of 16 or 17 years old will be eligible to participate if approved by the country or regulatory/health authorities. Note: Adolescent participants at the age of 16 or 17 years old must weigh ≥ 40 kilograms and meet the definition of Tanner Stage 5 at the Screening Visit. * Diagnosis of Ulcerative Colitis (UC) for 90 days or greater prior to Baseline, confirmed by colonoscopy during the Screening Period, with exclusion of current infection, colonic dysplasia and/or malignancy. Appropriate documentation of biopsy results consistent with the diagnosis of UC, 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. * Demonstrated an inadequate response, loss of response, or intolerance to at lease one of the following treatments including, oral aminosalicylates, corticosteroids, immunosuppressants, and/or biologic therapies. Note: Participants who have had inadequate response, loss of response to conventional therapy but have not failed biologic therapy (Non-bio-IR) and have received a prior biologic for up to 1 year may be enrolled, however they must have discontinued the biologic for reasons other than inadequate response or intolerance (e.g., change of insurance, well controlled disease), and must meet criteria for inadequate response, loss of response, or intolerance as defined above. * Female Participants of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit. * If female, participant must meet the contraception recommendation criteria. Exclusion Criteria: * Participant with current diagnosis of Crohn's disease (CD) or diagnosis of indeterminate colitis (IC). * Current diagnosis of fulminant colitis and/or toxic megacolon. * Participant with disease limited to the rectum (ulcerative proctitis) during the Screening endoscopy. * Received cyclosporine, tacrolimus, mycophenolate mofetil, or thalidomide within 30 days prior to Baseline. * Participant who received azathioprine or 6-mercaptopurine (6-MP) within 10 days of Baseline. * Received intravenous corticosteroids within 14 days prior to Screening or during the Screening Period. * Participant with previous exposure to Janus Activated Kinase (JAK) inhibitor (e.g., tofacitinib, baricitinib, filgotinib, upadacitinib). * Screening laboratory and other analyses show any prespecified abnormal hematologic results.

Locations (379)

Outcomes

Primary Outcomes

Percentage of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 8

The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). 3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. Clinical remission is defined as an Adapted Mayo score ≤ 2, with SFS ≤ 1 and not higher than Baseline, RBS of 0, and endoscopic subscore ≤ 1.

Time frame: Week 8

Secondary Outcomes

Percentage of Participants With Endoscopic Improvement at Week 8

Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).

Time frame: Week 8

Percentage of Participants With Endoscopic Remission at Week 8

Endoscopic remission is defined as an endoscopic subscore of 0. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).

Time frame: Week 8

Percentage of Participants Who Achieved Clinical Response Per Adapted Mayo Score at Week 8

The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). 3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 with higher scores representing more severe disease. Clinical response per the Adapted Mayo Score is defined as a decrease in Adapted Mayo score ≥ 2 points and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1.

Data from ClinicalTrials.gov

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