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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02819635
Recruitment Status : Completed
First Posted : June 30, 2016
Results First Posted : June 30, 2022
Last Update Posted : June 30, 2022
Sponsor:
Information provided by (Responsible Party):
AbbVie

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Ulcerative Colitis (UC) Drug: Placebo Drug: Upadacitinib Phase 2 Phase 3

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Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1302 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : September 26, 2016
Actual Primary Completion Date : December 13, 2021
Actual Study Completion Date : December 13, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Placebo Comparator: SS1: Placebo
During the 8-week induction phase in Substudy 1, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks.
 Drug: Placebo
Film-coated tablet for oral administration
Experimental: SS1: Upadacitinib 7.5 mg
During the 8-week induction phase in Substudy 1, participants received 7.5 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks.
 Drug: Upadacitinib
Film-coated tablet for oral administration
Other Names:
  • ABT-494
  • RINVOQ
Experimental: SS1: Upadacitinib 15 mg
During the 8-week induction phase in Substudy 1, participants received 15 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks.
 Drug: Upadacitinib
Film-coated tablet for oral administration
Other Names:
  • ABT-494
  • RINVOQ
Experimental: SS1: Upadacitinib 30 mg
During the 8-week induction phase in Substudy 1, participants received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks.
 Drug: Upadacitinib
Film-coated tablet for oral administration
Other Names:
  • ABT-494
  • RINVOQ
Experimental: SS1: Upadacitinib 45 mg
During the 8-week induction phase in Substudy 1, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks.
 Drug: Upadacitinib
Film-coated tablet for oral administration
Other Names:
  • ABT-494
  • RINVOQ
Experimental: SS2: Placebo/Upadacitinib 45 mg
During the Substudy 2 Part 1 induction period, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Participants who did not achieve clinical response at Week 8 of Part 1 were enrolled in an open-label extended treatment period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for an additional 8 weeks.
 Drug: Placebo
Film-coated tablet for oral administration

Drug: Upadacitinib
Film-coated tablet for oral administration
Other Names:
  • ABT-494
  • RINVOQ
Experimental: SS2: Upadacitinib 45 mg/Upadacitinib 45 mg
During the Substudy 2 Part 1 induction period, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Participants who did not achieve clinical response at Week 8 of Part 1 were enrolled in an open-label expended treatment period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for an additional 8 weeks.
 Drug: Upadacitinib
Film-coated tablet for oral administration
Other Names:
  • ABT-494
  • RINVOQ
Experimental: SS3: M14-675 clinical responders
Participants in Study M14-675 (NCT03653026) who achieved clinical response defined by Adapted Mayo Score at Week 8 or Week 16 in that study and did not meet any study discontinuation criteria were eligible to enroll into Substudy 3. Participants were re-randomized and treated with a blinded treatment assignment (15 mg upadacitinib film-coated tablets once daily by mouth [QD], or 30 mg upadacitinib film-coated tablets QD, or placebo for upadacitinib film-coated tablets QD) for up to 52 weeks.
 Drug: Placebo
Film-coated tablet for oral administration

Drug: Upadacitinib
Film-coated tablet for oral administration
Other Names:
  • ABT-494
  • RINVOQ


Outcome Measures
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Primary Outcome Measures :
  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:

    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.

    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:

    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.

    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:

    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.

    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 Outcome Measures :
  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:

    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 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:

    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).

    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:

    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 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:

    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).

    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:

    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.

    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:

    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.

    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:

    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 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.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   16 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02819635


Locations
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Sponsors and Collaborators
AbbVie
Investigators
Layout table for investigator information
Study Director: ABBVIE INC. AbbVie
  Study Documents (Full-Text)

Documents provided by AbbVie:
Study Protocol  [PDF] May 10, 2021
Statistical Analysis Plan  [PDF] May 20, 2021

More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02819635    
Other Study ID Numbers: M14-234
2016-000641-31 ( EudraCT Number )
First Posted: June 30, 2016    Key Record Dates
Results First Posted: June 30, 2022
Last Update Posted: June 30, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: For details on when studies are available for sharing, please refer to the link below.
Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Use Agreement (DUA). For more information on the process, or to submit a request, visit the following link.
URL: https://vivli.org/ourmember/abbvie/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AbbVie:
Upadacitinib (ABT-494)
Moderately to Severely Active UC
RINVOQ
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
 Pathologic Processes
Inflammatory Bowel Diseases
Upadacitinib
Janus Kinase Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents