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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02365649

Registration number

NCT02365649

Ethics application status

Date submitted

16/02/2015

Date registered

19/02/2015

Date last updated

27/12/2023

Titles & IDs

Public title

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of ABT-494 for the Induction of Symptomatic and Endoscopic Remission in Subjects With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Immunomodulators or Anti-TNF Therapy

Scientific title

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Upadacitinib (ABT-494) for the Induction of Symptomatic and Endoscopic Remission in Subjects With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Immunomodulators or Anti-TNF Therapy

Secondary ID [1]

2014-003240-12

Secondary ID [2]

M13-740

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Crohn's Disease

Condition category

Condition code

Oral and Gastrointestinal

Inflammatory bowel disease

Inflammatory and Immune System

Other inflammatory or immune system disorders

Oral and Gastrointestinal

Crohn's disease

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - Placebo
Treatment: Drugs - ABT-494

Active comparator: Induction Period ABT-494 Twice Daily Medium/High Dose - Induction Period ABT-494 Twice Daily Medium/High Dose orally dosed twice a day

Active comparator: Extension Phase ABT-494 High Dose - Extension Phase ABT-494 High Dose orally dosed twice a day

Placebo comparator: Induction Period Placebo - Induction Period Placebo orally dosed twice a day

Active comparator: Induction Period ABT-494 Low Dose - Induction Period ABT-494 Low Dose orally dosed twice a day

Active comparator: Induction Period ABT-494 Once Daily Medium/High Dose - Induction Period ABT-494 Once Daily Medium/High Dose orally dosed once a day

Active comparator: Extension Phase ABT-494 Low Dose - Extension Phase ABT-494 Low Dose orally dosed twice a day

Active comparator: Induction Period ABT-494 High Dose - Induction Period ABT-494 High Dose orally dosed twice a day

Active comparator: Induction Period ABT-494 Low/Medium Dose - Induction Period ABT-494 Low/Medium Dose orally dosed twice a day

Active comparator: Extension Phase ABT-494 Medium Dose - Extension Phase ABT-494 Medium Dose orally dosed twice a day

Treatment: Drugs: Placebo
Oral Dosing

Treatment: Drugs: ABT-494
Oral Dosing

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Percentage of Participants Who Achieve Endoscopic Remission at Week 12/16

Assessment method [1]

Endoscopic remission was determined using Simplified Endoscopic Score for Crohn's Disease (SES-CD). SES-CD subscores assess the following: presence and size of ulcers in 5 visualized bowel segments; extent of ulcerated surface in 5 visualized bowel segments; extent of affected surface in 5 visualized bowel segments; presence and type of narrowings in 5 visualized bowel segments. Subscores range from 0 to 15, and are summed for a total SES-CD score ranging from 0 to 56; higher scores indicate greater severity of mucosal inflammation. Endoscopic remission: SES-CD = 4 and at least 2-point reduction versus Baseline and no subscore \> 1 in any individual variable.

Timepoint [1]

Up to Week 16. (At Baseline, participants were allocated by randomization 1:1 to have their end of induction colonoscopy done at either Week 12 or Week 16; this endpoint combines the two time points.)

Primary outcome [2]

Percentage of Participants Who Achieve Clinical Remission at Week 16

Assessment method [2]

Clinical remission: average daily stool frequency = 1.5 and not worse than Baseline AND average daily abdominal pain = 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe).

Timepoint [2]

Week 16

Secondary outcome [1]

Percentage of Participants Who Achieve Crohn's Disease Activity Index (CDAI) < 150 at Week 16

Assessment method [1]

CDAI is used to quantify the signs and symptoms of subjects with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease. A score below 150 indicates remission.

Timepoint [1]

Week 16

Secondary outcome [2]

Percentage of Participants With a Decrease in CDAI = 70 Points From Baseline at Week 16

Assessment method [2]

Timepoint [2]

Week 16

Secondary outcome [3]

Percentage of Participants Who Achieve Clinical Remission at Week 12

Assessment method [3]

Timepoint [3]

Week 12

Secondary outcome [4]

Percentage of Participants Who Achieve Remission at Week 16

Assessment method [4]

Remission is defined as endoscopic remission at Week 12/16 AND clinical remission at Week 16. Endoscopic remission: SES-CD = 4 and at least 2-point reduction versus Baseline and no subscore \> 1 in any individual variable. Clinical remission: average daily stool frequency = 1.5 and not worse than Baseline AND average daily abdominal pain = 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint.

Timepoint [4]

Week 16

Secondary outcome [5]

Percentage of Participants Who Achieve Response at Week 16

Assessment method [5]

Response is defined as endoscopic response at Week 12/16 AND clinical response at Week 16. Endoscopic response: SES-CD at least 25% reduction from Baseline. Clinical response: average daily stool frequency at least 30% reduction from Baseline and average daily abdominal pain not worse than Baseline OR average daily abdominal pain at least 30% reduction from Baseline and average daily stool frequency not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint.

Timepoint [5]

Week 16

Secondary outcome [6]

Percentage of Participants With Endoscopic Response at Week 12/16

Assessment method [6]

Endoscopic response: SES-CD at least 25% reduction from Baseline. Details of the SES-CD scale are provided in the description of the first primary endpoint.

Timepoint [6]

Up to Week 16 (At Baseline, participants were allocated by randomization 1:1 to have their end of induction colonoscopy done at either Week 12 or Week 16; this endpoint combines the two time points.)

Secondary outcome [7]

Percentage of Participants Who Achieve Clinical Response at Week 16

Assessment method [7]

Clinical response: average daily stool frequency at least 30% reduction from Baseline and average daily abdominal pain not worse than Baseline OR average daily abdominal pain at least 30% reduction from Baseline and average daily stool frequency not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe).

Timepoint [7]

Week 16

Secondary outcome [8]

Percentage of Participants With an Average Daily Stool Frequency = 2.5 AND Average Daily Abdominal Pain = 2.0 at Baseline Who Achieve Clinical Remission at Week 16

Assessment method [8]

Timepoint [8]

Week 16

Secondary outcome [9]

Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve CDAI < 150 at Week 16

Assessment method [9]

Timepoint [9]

Week 16

Secondary outcome [10]

Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Remission at Week 12/16 and Clinical Remission at Week 16

Assessment method [10]

Timepoint [10]

Up to Week 16. (At Baseline, subjects were allocated by randomization 1:1 to have their end of induction colonoscopy done at either Week 12 or Week 16; this endpoint combines the two time points.)

Secondary outcome [11]

Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Clinical Remission at Week 16

Assessment method [11]

Timepoint [11]

Week 16

Secondary outcome [12]

Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Endoscopic Remission at Week 12/16

Assessment method [12]

Endoscopic remission: SES-CD = 4 and at least 2-point reduction versus Baseline and no subscore \> 1 in any individual variable. Details of the SES-CD scale are provided in the description of the first primary endpoint.

Timepoint [12]

Secondary outcome [13]

Change From Baseline in Fecal Calprotectin Level Over Time During the Induction Phase

Assessment method [13]

Timepoint [13]

Baseline, Week 4, Week 16

Secondary outcome [14]

Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) at Week 16

Assessment method [14]

Timepoint [14]

Baseline, Week 16

Secondary outcome [15]

Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Over Time During the Induction Phase

Assessment method [15]

Timepoint [15]

Baseline, Week 8, Week 16

Secondary outcome [16]

Percentage of Participants With Isolated Ileal Crohn's Disease at Baseline Who Achieve Remission at Week 16

Assessment method [16]

Remission is defined as endoscopic remission AND clinical remission. Endoscopic remission: SES-CD = 4 and at least 2-point reduction versus Baseline and no subscore \> 1 in any individual variable. Clinical remission: average daily stool frequency = 1.5 and not worse than Baseline AND average daily abdominal pain = 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint.

Timepoint [16]

Week 16

Secondary outcome [17]

Percentage of Participants With a Decrease in CDAI = 100 Points From Baseline at Week 16

Assessment method [17]

Timepoint [17]

Week 16

Secondary outcome [18]

Percentage of Participants Who Achieve > 50% Reduction From Baseline in SES-CD or Endoscopic Remission at Week 12/16

Assessment method [18]

Endoscopic remission: SES-CD = 4 and at least two point reduction versus Baseline and no subscore \> 1 in any individual variable. Details of the SES-CD scale are provided in the description of the first primary endpoint.

Timepoint [18]

Secondary outcome [19]

Percentage of Participants Who Achieve Modified Clinical Remission at Week 16 Among Participants With an Average Daily Stool Frequency = 4.0 or Average Daily Abdominal Pain = 2.0 at Baseline

Assessment method [19]

Modified clinical remission was defined as average daily stool frequency \<= 2.8 and not worse than Baseline and average daily abdominal pain \<= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe).

Timepoint [19]

Week 16

Secondary outcome [20]

Change From Baseline in Abdominal Pain Rating Scale at Week 12

Assessment method [20]

Abdominal pain was assessed on an abdominal pain rating scale, where subjects rated their average abdominal pain over the last 24 hours on a scale of 0 (none) to 10 (worst pain imaginable).

Timepoint [20]

Baseline, Week 12

Secondary outcome [21]

Change From Baseline in Abdominal Pain Rating Scale at Week 16

Assessment method [21]

Abdominal pain was assessed on an abdominal pain rating scale, where subjects rated their average abdominal pain over the last 24 hours on a scale of 0 (none) to 10 (worst pain imaginable).

Timepoint [21]

Baseline, Week 16

Secondary outcome [22]

Percentage of Participants Who Achieve Remission at Week 52

Assessment method [22]

Remission at Week 52 was defined as both endoscopic remission at Week 52 and clinical remission at Week 52. Endoscopic remission: SES-CD = 4 and at least 2-point reduction versus Baseline and no subscore \> 1 in any individual variable. Clinical remission: average daily stool frequency = 1.5 and not worse than Baseline AND average daily abdominal pain = 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). See SES-CD description details in the first primary endpoint description of this record. See definitions of responder and clinical responder in Outcome Measure 7 of this record.

Timepoint [22]

Week 52

Secondary outcome [23]

Percentage of Participants Who Achieve Endoscopic Remission at Week 52

Assessment method [23]

Timepoint [23]

Week 52

Secondary outcome [24]

Percentage of Participants Who Achieve Both Endoscopic Remission and Modified Clinical Remission at Week 52 Among Subjects With Daily Stool Frequency = 4.0 or Daily Abdominal Pain = 2.0 at Induction Baseline

Assessment method [24]

Endoscopic remission was defined as SES-CD \<= 4 and at least 2 points reduction versus induction baseline and no subscore \> 1 in any individual variable. Modified clinical remission was defined as average daily stool frequency \<= 2.8 and not worse than induction baseline AND average daily abdominal pain \<= 1.0 and not worse than induction baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). See SES-CD description details in the first primary endpoint description of this record.

Timepoint [24]

Week 52

Secondary outcome [25]

Percentage of Participants Who Achieve Clinical Remission Over Time During Extension Phase in Participants Receiving Upadacitinib in Induction

Assessment method [25]

Clinical remission was defined as average daily stool frequency \<= 1.5 and not worse than Induction Baseline and average daily abdominal pain \<= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe).

Timepoint [25]

Week 20, Week 28, Week 36, Week 44, Week 52

Secondary outcome [26]

Percentage of Participants Who Maintain Clinical Remission Over Time Among Participants in Clinical Remission at Week 16 in Participants Receiving Upadacitinib in Induction

Assessment method [26]

Timepoint [26]

Week 20, Week 28, Week 36, Week 44, Week 52

Secondary outcome [27]

Percentage of Participants Who Achieve Modified Clinical Remission Over Time During Extension Phase Among Participants With Daily Stool Frequency = 4.0 or Daily Abdominal Pain = 2.0 at Induction Baseline

Assessment method [27]

Modified clinical remission was defined as average daily stool frequency \<= 2.8 and not worse than Induction Baseline and average daily abdominal pain \<= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe).

Timepoint [27]

Week 20, Week 28, Week 36, Week 44, Week 52

Secondary outcome [28]

Percentage of Participants Who Achieve Modified Clinical Remission Over Time During Extension Phase Among Participants In Modified Clinical Remission At Week 16 and Daily Stool Frequency = 4.0 or Daily Abdominal Pain = 2.0 at Induction Baseline

Assessment method [28]

Timepoint [28]

Week 20, Week 28, Week 36, Week 44, Week 52

Secondary outcome [29]

Percentage of Participants Who Achieve Response at Week 52

Assessment method [29]

Response at Week 52 was defined as both endoscopic response at Week 52 and clinical response at Week 52. Endoscopic response: SES-CD at least 25% reduction from Baseline. Clinical response: average daily stool frequency at least 30% reduction from Induction Baseline and average daily abdominal pain not worse than Induction Baseline OR average daily abdominal pain at least 30% reduction from Induction Baseline and average daily stool frequency not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint.

Timepoint [29]

Week 52

Secondary outcome [30]

Percentage of Participants With SES-CD = 2 at Week 52

Assessment method [30]

SES-CD subscores assess the following: presence and size of ulcers in 5 visualized bowel segments; extent of ulcerated surface in 5 visualized bowel segments; extent of affected surface in 5 visualized bowel segments; presence and type of narrowings in 5 visualized bowel segments. Subscores range from 0 to 15, and are summed for a total SES-CD score ranging from 0 to 56; higher scores indicate greater severity of mucosal inflammation.

Timepoint [30]

Week 52

Secondary outcome [31]

Percentage of Participants With SES-CD = 0 at Week 52

Assessment method [31]

Timepoint [31]

Week 52

Secondary outcome [32]

Percentage of Participants Who Achieve Endoscopic Response at Week 52

Assessment method [32]

Endoscopic response was defined as SES-CD at least 25% reduction from Induction Baseline. SES-CD subscores assess the following: presence and size of ulcers in 5 visualized bowel segments; extent of ulcerated surface in 5 visualized bowel segments; extent of affected surface in 5 visualized bowel segments; presence and type of narrowings in 5 visualized bowel segments. Subscores range from 0 to 15, and are summed for a total SES-CD score ranging from 0 to 56; higher scores indicate greater severity of mucosal inflammation.

Timepoint [32]

Week 52

Secondary outcome [33]

Percentage of Participants Who Achieve Enhanced Endoscopic Response at Week 52

Assessment method [33]

Enhanced endoscopic response was defined as SES-CD reduction from Induction Baseline \> 50% (or for an Induction Baseline SES-CD of 4, at least a 2 point reduction from Induction Baseline). SES-CD subscores assess the following: presence and size of ulcers in 5 visualized bowel segments; extent of ulcerated surface in 5 visualized bowel segments; extent of affected surface in 5 visualized bowel segments; presence and type of narrowings in 5 visualized bowel segments. Subscores range from 0 to 15, and are summed for a total SES-CD score ranging from 0 to 56; higher scores indicate greater severity of mucosal inflammation.

Timepoint [33]

Week 52

Secondary outcome [34]

Percentage of Participants Who Achieve Endoscopic Improvement at Week 52

Assessment method [34]

Endoscopic Improvement: SES-CD reduction from Induction Baseline \> 50% or endoscopic remission. Endoscopic remission was defined as SES-CD \<= 4 and at least 2 points reduction versus Induction Baseline and no subscore \> 1 in any individual variable. SES-CD subscores assess the following: presence and size of ulcers in 5 visualized bowel segments; extent of ulcerated surface in 5 visualized bowel segments; extent of affected surface in 5 visualized bowel segments; presence and type of narrowings in 5 visualized bowel segments. Subscores range from 0 to 15, and are summed for a total SES-CD score ranging from 0 to 56; higher scores indicate greater severity of mucosal inflammation.

Timepoint [34]

Week 52

Secondary outcome [35]

Percentage of Participants Who Achieve Endoscopic Healing at Week 52

Assessment method [35]

Endoscopic healing was defined as SES-CD ulcerated surface subscore of 0 in subjects with SES-CD ulcerated surface subscore \>= 1 at Induction Baseline. SES-CD subscores assess the following: presence and size of ulcers in 5 visualized bowel segments; extent of ulcerated surface in 5 visualized bowel segments; extent of affected surface in 5 visualized bowel segments; presence and type of narrowings in 5 visualized bowel segments. Subscores range from 0 to 15, and are summed for a total SES-CD score ranging from 0 to 56; higher scores indicate greater severity of mucosal inflammation.

Timepoint [35]

Week 52

Secondary outcome [36]

Percentage of Participants Who Achieve Clinical Response Over Time During Extension Phase

Assessment method [36]

Clinical response was defined as average daily stool frequency at least 30% reduction from Induction Baseline and average daily abdominal pain not worse than Induction Baseline OR average daily abdominal pain at least 30% reduction from Induction Baseline and average daily stool frequency not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe).

Timepoint [36]

Week 20, Week 28, Week 36, Week 44, Week 52

Secondary outcome [37]

Percentage of Participants Who Achieve Enhanced Clinical Response Over Time During Extension Phase

Assessment method [37]

Enhanced clinical response was defined as average daily stool frequency at least 60% reduction from Induction Baseline and average daily abdominal pain not worse than Induction Baseline OR average daily abdominal pain at least 35% reduction from Induction Baseline and average daily stool frequency not worse than Induction Baseline or modified clinical remission (average daily stool frequency = 2.8 and not worse than Induction baseline AND average daily abdominal pain = 1.0 and not worse than Induction baseline). The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe).

Timepoint [37]

Week 20, Week 28, Week 36, Week 44, Week 52

Secondary outcome [38]

Percentage of Participants Who Achieve Enhanced Clinical Response Over Time During Extension Phase Among Participants In Enhanced Clinical Response At Week 16

Assessment method [38]

Enhanced clinical response was defined as average daily stool frequency at least 60% reduction from Induction Baseline and average daily abdominal pain not worse than Induction Baseline or average daily abdominal pain at least 35% reduction from Induction Baseline and average daily stool frequency not worse than Induction Baseline or modified clinical remission (average daily stool frequency = 2.8 and not worse than Induction baseline AND average daily abdominal pain = 1.0 and not worse than Induction baseline). The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe).

Timepoint [38]

Week 20, Week 28, Week 36, Week 44, Week 52

Secondary outcome [39]

Percentage of Participants Who Achieve Clinical Remission Over Time During Extension Phase Among Participants With an Average Daily Stool Frequency = 2.5 and Average Daily Abdominal Pain = 2.0 at Induction Baseline

Assessment method [39]

Clinical remission was defined as average daily stool frequency \<= 1.5 and not worse than Induction Baseline AND average daily abdominal pain \<= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe).

Timepoint [39]

Week 20, Week 28, Week 36, Week 44, Week 52

Secondary outcome [40]

Percentage of Participants Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve CDAI < 150 Over Time

Assessment method [40]

Timepoint [40]

Week 20, Week 28, Week 36, Week 44, Week 52

Secondary outcome [41]

Percentage of Participants Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Remission At Week 52

Assessment method [41]

Steroid-free remission at Week 52 was defined as both endoscopic remission at Week 52 and clinical remission at Week 52. Endoscopic remission: SES-CD = 4 and at least 2 point reduction versus Induction Baseline and no subscore \> 1 in any individual variable. Clinical remission: Average daily stool frequency = 1.5 and not worse than baseline AND average daily abdominal pain = 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). See SES-CD description details in the first primary endpoint description of this record.

Timepoint [41]

Baseline, Week 52

Secondary outcome [42]

Percentage of Participants Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Clinical Remission Over Time

Assessment method [42]

Steroid-free clinical remission was defined as average daily stool frequency \<= 1.5 and not worse than Induction Baseline AND average daily abdominal pain \<= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe).

Timepoint [42]

Week 20, Week 28, Week 36, Week 44, Week 52

Secondary outcome [43]

Percentage of Participants Taking Corticosteroids at Induction Baseline and With Daily Stool Frequency = 4.0 or Daily Abdominal Pain = 2.0 at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Modified Clinical Remission Over Time

Assessment method [43]

Steroid-free modified clinical remission was defined as average daily stool frequency \<= 2.8 and not worse than Induction Baseline AND average daily abdominal pain \<= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe).

Timepoint [43]

Week 20, Week 28, Week 36, Week 44, Week 52

Secondary outcome [44]

Percentage of Participants Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Endoscopic Remission at Week 52

Assessment method [44]

Steroid-free endoscopic remission was defined as SES-CD \<= 4 and at least 2 points reduction versus Induction Baseline and no subscore \> 1 in any individual variable. Details of the SES-CD scale are provided in the description of the first primary endpoint.

Timepoint [44]

Baseline, Week 52

Secondary outcome [45]

Percentage Of Participants Who Achieve CDAI < 150 Over Time During Extension Phase

Assessment method [45]

Timepoint [45]

Week 20, Week 28, Week 36, Week 44, Week 52

Secondary outcome [46]

Percentage of Participants With Decrease in CDAI = 70 Points From Induction Baseline Over Time During Extension Phase

Assessment method [46]

Timepoint [46]

Week 20, Week 28, Week 36, Week 44, Week 52

Secondary outcome [47]

Change From Induction Baseline in Fecal Calprotectin Level Over Time During Extension Phase

Assessment method [47]

Timepoint [47]

Baseline, Week 28, Week 52

Secondary outcome [48]

Change From Induction Baseline in Hs-CRP Over Time During Extension Phase

Assessment method [48]

Timepoint [48]

Baseline, Week 20, Week 28, Week 36, Week 44, Week 52

Secondary outcome [49]

Change From Induction Baseline in IBDQ at Week 52

Assessment method [49]

The IBDQ is a disease-specific instrument composed of 32 Likert-scaled items. The total score ranges from 32 to 224 using the 7-point response options, with higher scores indicating better health-related quality of life. The IBDQ scale contains 4 component subscales: bowel symptoms, systemic symptoms, emotional function, and social function. Each subscale can be computed with total scores ranging from 10 to 70, 5 to 35, 12 to 84, and 5 to 35, respectively.

Timepoint [49]

Baseline, Week 52

Secondary outcome [50]

Change From Induction Baseline in European Quality of Life (EuroQol) 5 Dimensions Questionnaire (EQ-5D) Index Score at Week 52

Assessment method [50]

The EQ-5D is a standardized instrument for use as a measure of health-related quality of life. The EQ-5D Index Score has five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Health states are converted into a weighted health state index. These weights lie on a scale on which full health has a value of 1 and dead has a value of 0. A positive change represents an improvement in health-related quality of life.

Timepoint [50]

Baseline, Week 52

Secondary outcome [51]

Change From Induction Baseline in EQ-5D VAS at Week 52

Assessment method [51]

The EQ-5D is a standardized instrument for use as a measure of health-related quality of life. The EQ-5D VAS is a 20-cm scale with endpoints labeled "best imaginable health" and "worst imaginable health" anchored at 100 and 0, respectively. A positive change represents an improvement in health-related quality of life.

Timepoint [51]

Baseline, Week 52

Secondary outcome [52]

Cross Tabulation of Induction Baseline and Week 52 in Total Number of Extra-Intestinal Manifestations (EIMs) of Crohn's Disease

Assessment method [52]

Presented as percentage of participants with given number of EIMs at Baseline (BL) and Week (Wk) 52. EIMs of Crohn's disease included anemia, autoimmune hepatitis, axial arthropathy, bronchiectasis, chronic obstructive pulmonary disease, episcleritis, erythema nodosum, iritis, nephrolithiasis, oral aphthous ulcers, peripheral arthropathy, primary sclerosing cholangitis, pyoderma gangrenosum, Sweet's syndrome, uveitis, and venous thromboembolism.

Timepoint [52]

Baseline, Week 52

Secondary outcome [53]

Percentage of Participants Who Achieve Remission at Week 52 Among Participants With Isolated Ileal Crohn's Disease at Baseline

Assessment method [53]

Remission at Week 52 is defined as endoscopic remission at Week 52 AND clinical remission at Week 52. Endoscopic remission: SES-CD = 4 and at least 2-point reduction versus Baseline and no subscore \> 1 in any individual variable. Clinical remission: average daily stool frequency = 1.5 and not worse than Baseline AND average daily abdominal pain = 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint.

Timepoint [53]

Baseline, Week 52

Secondary outcome [54]

Percentage of Participants Who Achieve Modified Clinical Remission at Week 52 Among Participants With Isolated Ileal Crohn's Disease at Baseline And Daily Stool Frequency = 4.0 or Daily Abdominal Pain = 2.0 at Induction Baseline

Assessment method [54]

Modified clinical remission was defined as average daily stool frequency \<= 2.8 and not worse than induction baseline AND average daily abdominal pain \<= 1.0 and not worse than induction baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe).

Timepoint [54]

Week 52

Eligibility

Key inclusion criteria

1. Diagnosis of Crohn's disease (CD) for at least 90 days.
2. Crohn's Disease Activity Index (CDAI) greater than or equal to 220 and less than or equal to 450.
3. Subject inadequately responded to or experienced intolerance to previous treatment with immunomodulators (e.g. azathioprine, 6-mercaptopurine, or methotrexate) and/or anti-TNF agent (e.g., infliximab, adalimumab, or certolizumab pegol).

Minimum age

18 Years

Maximum age

75 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Subjects with ulcerative colitis (UC), collagenous colitis or indeterminate colitis.
2. Subject who has had surgical bowel resections in the past 6 months or is planning resection.
3. Subjects with an ostomy or ileoanal pouch.
4. Subject with symptomatic bowel stricture or abdominal or peri-anal abcess.
5. Subject who has short bowel syndrome.
6. Subject with recurring infections or active Tuberculosis (TB).

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 2

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

17/03/2015

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

3/08/2017

Sample size

Target

Accrual to date

Final

220

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Primary sponsor type

Commercial sector/industry

Name

AbbVie

Country

Ethics approval

Ethics application status

Summary

Brief summary

To determine the efficacy and safety of multiple doses of ABT-494 in subjects with moderately to severely active Crohn's Disease with a history of inadequate response to or intolerance to Immunomodulators or anti-Tumor Necrosis Factor (TNF) therapy.

Trial website

https://clinicaltrials.gov/study/NCT02365649

Trial related presentations / publications

Sandborn WJ, Lewis JD, Panes J, Loftus EV, D'Haens G, Yu Z, Huang B, Lacerda AP, Pangan AL, Feagan BG. Association Between Proposed Definitions of Clinical Remission/Response and Well-Being in Patients With Crohn's Disease. J Crohns Colitis. 2022 Mar 14;16(3):444-451. doi: 10.1093/ecco-jcc/jjab161.
Aguilar D, Revilla L, Garrido-Trigo A, Panes J, Lozano JJ, Planell N, Esteller M, Lacerda AP, Guay H, Butler J, Davis JW, Salas A. Randomized Controlled Trial Substudy of Cell-specific Mechanisms of Janus Kinase 1 Inhibition With Upadacitinib in the Crohn's Disease Intestinal Mucosa: Analysis From the CELEST Study. Inflamm Bowel Dis. 2021 Nov 15;27(12):1999-2009. doi: 10.1093/ibd/izab116.
Peyrin-Biroulet L, Louis E, Loftus EV Jr, Lacerda A, Zhou Q, Sanchez Gonzalez Y, Ghosh S. Quality of Life and Work Productivity Improvements with Upadacitinib: Phase 2b Evidence from Patients with Moderate to Severe Crohn's Disease. Adv Ther. 2021 May;38(5):2339-2352. doi: 10.1007/s12325-021-01660-7. Epub 2021 Mar 23.
Sandborn WJ, Feagan BG, Loftus EV Jr, Peyrin-Biroulet L, Van Assche G, D'Haens G, Schreiber S, Colombel JF, Lewis JD, Ghosh S, Armuzzi A, Scherl E, Herfarth H, Vitale L, Mohamed MF, Othman AA, Zhou Q, Huang B, Thakkar RB, Pangan AL, Lacerda AP, Panes J. Efficacy and Safety of Upadacitinib in a Randomized Trial of Patients With Crohn's Disease. Gastroenterology. 2020 Jun;158(8):2123-2138.e8. doi: 10.1053/j.gastro.2020.01.047. Epub 2020 Feb 8.

Public notes

 This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts

Principal investigator

Name

AbbVie Inc.

Address

AbbVie

Country

Phone

Contact person for public queries

Name

Address

Country

Phone

Contact person for scientific queries

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Undecided

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

Type	Other Details	Attachment
Study protocol		https://cdn.clinicaltrials.gov/large-docs/49/NCT02365649/Prot_000.pdf
Statistical analysis plan		https://cdn.clinicaltrials.gov/large-docs/49/NCT02365649/SAP_001.pdf

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT02365649

Trial Review

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02365649