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NCT Number: NCT02819635

A Study to Evaluate the Safety and Efficacy of Upadacitinib (ABT-494) for Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis (UC)

This study was comprised of three substudies. The objective of Substudy 1 was to characterize the dose-response, efficacy, and safety of upadacitinib compared to placebo in inducing clinical remission to identify the induction dose of upadacitinib for further evaluation in Substudy 2. The objective of Substudy 2 was to evaluate the efficacy and safety of upadacitinib compared to placebo in inducing clinical remission in participants. The objective of Substudy 3 was to evaluate the efficacy and safety of upadacitinib compared to placebo in achieving clinical remission in participants who had a response following induction with upadacitinib.

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Key information

Conditions

Ulcerative Colitis (UC) Colitis Colitis, Ulcerative Colonic Diseases Digestive System Diseases Gastroenteritis Gastrointestinal Diseases Inflammatory Bowel Diseases Intestinal Diseases

Age range

16 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Cardio Alem /ID# 211280, San Isidro, Buenos Aires, Argentina

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About this study

Substudy 1 was a Phase 2b dose-ranging study designed to evaluate the efficacy and safety of different oral doses of upadacitinib compared to placebo as 8-week induction therapy in participants with moderately to severely active UC. Approximately 250 participants were planned to be randomized 1:1:1:1:1 to the placebo group and 4 upadacitinib doses (7.5, 15, 30, and 45 mg). Randomization was stratified by previous biologic therapy use (yes/no), Baseline corticosteroid use (yes/no), and Baseline Adapted Mayo score (≤ 7 or > 7). The study duration included a Screening Period of up to 5 weeks and an 8-week double-blind (DB) Induction Period. After all randomized participants completed the 8-week induction, a dose-selection analysis of efficacy and safety (selected laboratory parameters) of upadacitinib versus placebo was performed. Based on this dose-selection analysis, one induction dose (upadacitinib 45 mg) was identified for further evaluation in two Phase 3 induction studies, M14-234 Substudy 2 and M14-675 (NCT03653026). During the analysis period, 132 additional participants were randomized into Groups 3 and 4 of Substudy 1 (upadacitinib 30 mg and 45 mg dose groups; approximately 66 participants per dose group). The objectives of enrolling these additional participants were to avoid interrupting the study activities during the analysis period and to support a sufficient number of participants with clinical response to be re-randomized into the maintenance portion in Substudy 3. Substudy 1 main participants are defined as those first 250 randomized 250, and additional participants are defined as those who were randomized after the main participants.

Substudy 2 was a two-part Phase 3 dose-confirming study designed to evaluate the efficacy and safety of oral administration of upadacitinib 45 mg compared to placebo as induction therapy for up to 16 weeks in participants with moderately to severely active UC. Substudy 2 included a Screening Period of up to 5 weeks, Part 1, and Part 2. Part 1 was a randomized, DB, placebo-controlled 8-week induction period. Part 2 was an open-label, 8-week extended treatment period for clinical non-responders from Part 1 of Substudy 2. Part 1 was planned to enroll 462 subjects; actual enrollment was 474 subjects. Eligible participants were randomized in a 2:1 ratio to one of the two treatment groups (DB upadacitinib 45 mg or matching placebo) for 8 weeks. The randomization was stratified by bio-IR status (Biologic inadequate responders [bio-IR] vs Non-biologic-inadequate responders [non-bio-IR], corticosteroid use (yes or no), and Adapted Mayo score (≤ 7 or > 7) at Baseline. Within bio-IR, the randomization was further stratified by number of prior biologic treatments (≤ 1 or > 1). Within non-bio-IR, the randomization was further stratified by previous biologic use (yes or no). Part 2 was an open label, 8-week Extended Treatment Period for those who did not achieve clinical response per Adapted Mayo score at Week 8 in Part 1. All participants received upadacitinib 45 mg.

Substudy 3 was a Phase 3 maintenance study designed to evaluate the efficacy and safety of upadacitinib 15 and 30 mg once daily (QD) compared to placebo in achieving clinical remission per Adapted Mayo score in participants with moderately to severely active UC who achieved clinical response per Adapted Mayo score following induction therapy from Substudy 1, Substudy 2, or Study M14-675. A total of 1,046 subjects who achieved clinical response per Adapted Mayo score after completion of induction treatment or Extended Treatment Period in Study M14-234 Substudy 1, Substudy 2, or Study M14-675 entered Substudy 3, and 1,044 were treated with a blinded treatment assignment for up to 52 weeks. Substudy 3 included 4 cohorts. Cohort 1: 847 participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at either Week 8 or Week 16, and received upadacitinib 15, 30, or 45 mg QD. The treatment groups in Cohort 1 were Group 1: upadacitinib 15 mg QD; Group 2: upadacitinib 30 mg QD; and Group 3: placebo QD. Those who achieved clinical response and received upadacitinib 15 mg QD in Substudy 1 were re-randomized 1:1 to only receive upadacitinib 15 mg QD or placebo QD (treatment Group 1 or 3). Cohort 2: 104 participants who received double-blind placebo QD treatment for 8 weeks during Substudy 1, Substudy 2 Part 1, or Study M14-675 Part 1 and achieved clinical response at Week 8 continued to receive blinded placebo QD in Substudy 3. Cohort 3: 75 participants who received upadacitinib 45 mg QD in Induction Phase and did not achieve clinical response and received upadacitinib 45 mg QD in Extended Treatment in Substudy 2 Part 2 or in Study M14-675 Part 2 and achieved clinical response at Week 16 were re-randomized 1:1 and received blinded upadacitinib 30 mg QD or upadacitinib 15 mg QD in Substudy 3. Cohort 4: 20 participants who received double-blinded treatment of upadacitinib 7.5 mg QD for 8 weeks during Substudy 1 and achieved clinical response at Week 8 continued to receive blinded treatment of upadacitinib 7.5 mg QD in Substudy 3.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Note: Adolescent participants who are 16 or 17 years old will be eligible to participate if approved by the country or regulatory/health authority. If approval has not been granted, only participants ≥18 years old will be enrolled. Adolescents must weigh ≥ 40 kilograms and meet the definition of Tanner Stage 5 at Screening Visit.

  • Diagnosis of ulcerative colitis 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 ulcerative colitis with an Adapted Mayo score of 5 to 9 points and endoscopic sub score of 2 to 3 (confirmed by central reader).
  • Demonstrated an inadequate response to, loss of response to, or intolerance to at least one of the following treatments including: oral aminosalicylates, corticosteroids, immunosuppressants, and/or biologic therapies in the opinion of the investigator.

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 to aminosalicylates, corticosteroids, and/or immunosuppressants as defined above.

  • If female, participant must meet the criteria for Contraception Recommendations
  • 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 prior to study drug dosing.

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 on azathioprine or 6-mercaptopurine 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 abnormal results meeting the exclusion criteria

Treatment and study plan

Placebo

Drug

Film-coated tablet for oral administration

Upadacitinib

Drug

Film-coated tablet for oral administration

Other names: ABT-494, RINVOQ

Primary outcomes

  1. Substudy 1: Percentage Of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 8

    Time frame: At Week 8

    The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores:

    • Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal)
    • Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed)
    • 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.

    For Substudy 1, clinical remission is defined as SFS ≤ 1, RBS of 0, and endoscopic subscore ≤ 1.

  2. Substudy 2: Percentage Of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 8

    Time frame: At Week 8

    The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores:

    • Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal)
    • Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed)
    • 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.

    For Substudy 2, clinical remission is defined as SFS ≤ 1 and not greater than Baseline, RBS of 0, and endoscopic subscore ≤ 1. In Substudy 2, evidence of friability during endoscopy in participants with otherwise "mild" endoscopic activity conferred an endoscopic subscore of 2.

  3. Substudy 3: Percentage Of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 52

    Time frame: At Week 52

    The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores:

    • Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal).
    • Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed).
    • 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.

    For Substudy 3, clinical remission is defined as SFS ≤ 1 and not greater than Baseline, RBS of 0, and endoscopic subscore ≤ 1. In addition, evidence of friability during endoscopy in participants with otherwise "mild" endoscopic activity conferred an endoscopic subscore of 2.

Secondary outcomes

  1. Substudy 1: Percentage Of Participants With Endoscopic Improvement at Week 8

    Time frame: 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).

  2. Substudy 1: Percentage Of Participants Achieving Clinical Remission Per Full Mayo Score at Week 8

    Time frame: At Week 8

    The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Full Mayo score (FMS) ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore > 1.

  3. Substudy 1: Percentage Of Participants Achieving Clinical Response Per Adapted Mayo Score at Week 8

    Time frame: At Week 8

    The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores:

    • Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal).
    • Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed).
    • 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 response is defined as a decrease from baseline in the Adapted Mayo score ≥ 2 points and ≥ 30% from baseline, and a decrease in RBS ≥ 1 or an absolute RBS ≤ 1).

  4. Substudy 1: Percentage Of Participants Achieving Clinical Response Per Partial Mayo Score at Week 2

    Time frame: At Week 2

    The Partial Mayo Score is a composite score of UC disease activity based on the following 2 subscores:

    • Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal).
    • Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed).

    The overall Partial Mayo score ranges from 0 to 6 with higher scores representing more severe disease.

    Clinical response per Partial Mayo Score is defined as a decrease in Partial Adapted Mayo score ≥ 2 points and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1.

  5. Substudy 1: Change in Full Mayo Score From Baseline to Week 8

    Time frame: Baseline (Week 0), Week 8

    The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Full Mayo score (FMS) ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore > 1.

  6. Substudy 1: Percentage Of Participants With Endoscopic Remission at Week 8

    Time frame: 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).

  7. Substudy 1: Percentage Of Participants Who Achieved Histologic Improvement at Week 8

    Time frame: At Week 8

    The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.

    Histologic improvement was defined as decrease from baseline in Geboes score.

  8. Substudy 2: Percentage Of Participants With Endoscopic Improvement at Week 8

    Time frame: 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).

  9. Substudy 2: Percentage Of Participants With Endoscopic Remission at Week 8

    Time frame: 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).

  10. Substudy 2: Percentage Of Participants Achieving Clinical Response Per Adapted Mayo Score at Week 8

    Time frame: At Week 8

    The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores:

    • Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal).
    • Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed).
    • 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 response is defined as a decrease from baseline in the Adapted Mayo score ≥ 2 points and ≥ 30% from baseline, and a decrease in RBS ≥ 1 or an absolute RBS ≤ 1).

  11. Substudy 2: Percentage Of Participants Achieving Clinical Response Per Partial Mayo Score at Week 2

    Time frame: At Week 2

    The Partial Mayo Score is a composite score of UC disease activity based on the following 2 subscores:

    • Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal).
    • Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed).

    The overall Partial Mayo score ranges from 0 to 6 with higher scores representing more severe disease.

    Clinical response per Partial Mayo Score is defined as a decrease from Baseline ≥ 1 point and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1.

  12. Substudy 2: Percentage Of Participants Who Achieved Histologic-Endoscopic Mucosal Improvement at Week 8

    Time frame: At Week 8

    Histologic-endoscopic mucosal improvement is defined as an endoscopic subscore of 0 or 1 and a Geboes score ≤ 3.1.

    The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration).

    The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.

  13. Substudy 2: Percentage Of Participants Who Report No Bowel Urgency at Week 8

    Time frame: At Week 8

    Bowel urgency was assessed by participants in a subject diary completed once a day.

  14. Substudy 2: Percentage Of Participants Who Reported No Abdominal Pain at Week 8

    Time frame: At Week 8

    Abdominal pain was assessed by participants in a subject diary completed once a day.

  15. Substudy 2: Percentage Of Participants Who Achieved Histologic Improvement at Week 8

    Time frame: At Week 8

    The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration. Histologic improvement was defined as decrease from baseline in Geboes score.

  16. Substudy 2: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 8

    Time frame: Baseline (Week 0), Week 8

    The Inflammatory Bowel Disease Questionnaire (IBDQ) is used to assess health-related quality of life (HRQoL) in patients with ulcerative colitis. It consists of 32 questions evaluating bowel and systemic symptoms, as well as emotional and social functions. Each question is answered on a scale from 1 (worst) to 7 (best). The total score ranges from 32 to 224 with higher scores indicating better health-related quality of life. A positive change from Baseline indicates improvement.

  17. Substudy 2: Percentage Of Participants With Mucosal Healing at Week 8

    Time frame: At Week 8

    Mucosal healing is defined as an endoscopic score of 0 and Geboes score < 2.0. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration).

    The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.

  18. Substudy 2: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 8

    Time frame: Baseline (Week 0), Week 8

    The FACIT fatigue questionnaire was developed to assess fatigue associated with anemia. It consists of 13 fatigue-related questions. Each question is answered on a 5-point Likert scale: 0 (not at all); 1 (a little bit); 2 (somewhat); 3 (quite a bit); and 4 (very much). The total score ranges from 0 to 52, where higher scores represent less fatigue, and a positive change from Baseline indicates improvement.

  19. Substudy 3: Percentage Of Participants With Endoscopic Improvement at Week 52

    Time frame: At Week 52

    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).

  20. Substudy 3: Percentage of Participants With Clinical Remission Per Adapted Mayo Score at Week 52 Among Those Who Achieved Clinical Remission at the End of the Induction Treatment

    Time frame: At Week 52

    The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores:

    • Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal).
    • Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed).
    • 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.

    For Substudy 3, clinical remission is defined as SFS ≤ 1 and not greater than Baseline, RBS of 0, and endoscopic subscore ≤ 1. In addition, evidence of friability during endoscopy in participants with otherwise "mild" endoscopic activity conferred an endoscopic subscore of 2.

  21. Substudy 3: Percentage of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Wk 52 and Were Corticosteroid Free for ≥ 90 Days Immediately Preceding Wk 52 Among Those Who Achieved Clinical Remission at the End of the Induction Treatment

    Time frame: At Week 52

    The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores:

    • Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal).
    • Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed).
    • 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.

    For Substudy 3, clinical remission is defined as SFS ≤ 1 and not greater than Baseline, RBS of 0, and endoscopic subscore ≤ 1. In addition, evidence of friability during endoscopy in participants with otherwise "mild" endoscopic activity conferred an endoscopic subscore of 2.

  22. Substudy 3: Percentage of Participants With Endoscopic Improvement at Wk 52 Among Those Who Achieved Endoscopic Improvement at the End of the Induction Treatment

    Time frame: At Week 52

    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).

  23. Substudy 3: Percentage Of Participants With Endoscopic Remission At Week 52

    Time frame: At Week 52

    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).

  24. Substudy 3: Percentage Of Participants Who Maintained Clinical Response Per Adapted Mayo Score at Wk 52 Among Those Who Achieved Clinical Response at the End of the Induction Treatment

    Time frame: At Week 52

    The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores:

    • Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal).
    • Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed).
    • 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 response is defined as a decrease from baseline in the Adapted Mayo score ≥ 2 points and ≥ 30% from baseline, and a decrease in RBS ≥ 1 or an absolute RBS ≤ 1).

  25. Substudy 3: Percentage Of Participants Who Achieved Histologic-Endoscopic Mucosal Improvement at Week 52

    Time frame: At Week 52

    Histologic-endoscopic mucosal improvement is defined as an endoscopic subscore of 0 or 1 and a Geboes score ≤ 3.1.

    The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration).

    The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.

  26. Substudy 3: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 52

    Time frame: Baseline (Week 0), Week 52

    The Inflammatory Bowel Disease Questionnaire (IBDQ) is used to assess health-related quality of life (HRQoL) in patients with ulcerative colitis. It consists of 32 questions evaluating bowel and systemic symptoms, as well as emotional and social functions. Each question is answered on a scale from 1 (worst) to 7 (best). The total score ranges from 32 to 224 with higher scores indicating better health-related quality of life. A positive change from Baseline indicates improvement.

  27. Substudy 3: Percentage Of Participants With Mucosal Healing at Week 52

    Time frame: At Week 52

    Mucosal healing is defined as an endoscopic score of 0 and Geboes score < 2.0. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration).

    The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.

  28. Substudy 3: Percentage Of Participants Who Reported No Bowel Urgency at Week 52

    Time frame: At Week 52

    Bowel urgency was assessed by participants in a subject diary completed once a day.

  29. Substudy 3: Percentage Of Participants Who Reported No Abdominal Pain at Week 52

    Time frame: At Week 52

    Abdominal pain was assessed by participants in a subject diary completed once a day.

  30. Substudy 3: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 52

    Time frame: Baseline (Week 0), Week 52

    The FACIT fatigue questionnaire was developed to assess fatigue associated with anemia. It consists of 13 fatigue-related questions. Each question is answered on a 5-point Likert scale: 0 (not at all); 1 (a little bit); 2 (somewhat); 3 (quite a bit); and 4 (very much). The total score ranges from 0 to 52, where higher scores represent less fatigue, and a positive change from Baseline indicates improvement.

Sponsors and collaborators

Lead sponsor

AbbVie

Industry

Registry information

Official study title

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Upadacitinib (ABT-494) for Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis

Important dates

Study start
2016
Primary completion
2021
Study completion
2021
First posted
Jun 30, 2016
Registry last updated
Jun 30, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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