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NCT02365649

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

Completed Phase 2 Results posted Last updated 27 December 2023
What this trial tests

Phase 2 trial testing Placebo in Crohn's Disease in 220 participants. Completed in 3 August 2017.

Timeline
17 March 2015
Primary endpoint
25 November 2016
3 August 2017

Quick facts

Lead sponsorAbbVie
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment220
Start date17 March 2015
Primary completion25 November 2016
Estimated completion3 August 2017

Drugs / interventions tested

Conditions studied

Sponsor

AbbVie — full company profile →

Who can join

Adults 18 to 75, any sex, with Crohn's Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Who Achieve Endoscopic Remission at Week 12/16 Primary · 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.)

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 reducti

GroupValue95% CI
Double-Blind Induction Phase: Placebo BID0
Double-Blind Induction Phase: Upadacitinib 3 mg BID10.3
Double-Blind Induction Phase: Upadacitinib 6 mg BID8.1
Double Blind Induction Phase: Upadacitinib 12 mg BID8.3
Double Blind Induction Phase: Upadacitinib 24 mg BID22.2
Double Blind Induction Phase: Upadacitinib 24 mg QD14.3
Percentage of Participants Who Achieve Clinical Remission at Week 16 Primary · Week 16

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).

GroupValue95% CI
Double-Blind Induction Phase: Placebo BID10.8
Double-Blind Induction Phase: Upadacitinib 3 mg BID12.8
Double-Blind Induction Phase: Upadacitinib 6 mg BID27.0
Double Blind Induction Phase: Upadacitinib 12 mg BID11.1
Double Blind Induction Phase: Upadacitinib 24 mg BID22.2
Double Blind Induction Phase: Upadacitinib 24 mg QD14.3
Percentage of Participants Who Achieve Crohn's Disease Activity Index (CDAI) < 150 at Week 16 Secondary · Week 16

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.

GroupValue95% CI
Double-Blind Induction Phase: Placebo BID16.2
Double-Blind Induction Phase: Upadacitinib 3 mg BID20.5
Double-Blind Induction Phase: Upadacitinib 6 mg BID29.7
Double Blind Induction Phase: Upadacitinib 12 mg BID38.9
Double Blind Induction Phase: Upadacitinib 24 mg BID30.6
Double Blind Induction Phase: Upadacitinib 24 mg QD20.0
Percentage of Participants With a Decrease in CDAI ≥ 70 Points From Baseline at Week 16 Secondary · Week 16

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 70-point decrease in the CDAI index refers to improvement in the disease activity from Baseline.

GroupValue95% CI
Double-Blind Induction Phase: Placebo BID35.1
Double-Blind Induction Phase: Upadacitinib 3 mg BID46.2
Double-Blind Induction Phase: Upadacitinib 6 mg BID54.1
Double Blind Induction Phase: Upadacitinib 12 mg BID44.4
Double Blind Induction Phase: Upadacitinib 24 mg BID61.1
Double Blind Induction Phase: Upadacitinib 24 mg QD48.6
Percentage of Participants Who Achieve Clinical Remission at Week 12 Secondary · Week 12

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).

GroupValue95% CI
Double-Blind Induction Phase: Placebo BID10.8
Double-Blind Induction Phase: Upadacitinib 3 mg BID10.3
Double-Blind Induction Phase: Upadacitinib 6 mg BID29.7
Double Blind Induction Phase: Upadacitinib 12 mg BID13.9
Double Blind Induction Phase: Upadacitinib 24 mg BID25.0
Double Blind Induction Phase: Upadacitinib 24 mg QD8.6
Percentage of Participants Who Achieve Remission at Week 16 Secondary · Week 16

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

GroupValue95% CI
Double-Blind Induction Phase: Placebo BID0.0
Double-Blind Induction Phase: Upadacitinib 3 mg BID2.6
Double-Blind Induction Phase: Upadacitinib 6 mg BID5.4
Double Blind Induction Phase: Upadacitinib 12 mg BID2.8
Double Blind Induction Phase: Upadacitinib 24 mg BID8.3
Double Blind Induction Phase: Upadacitinib 24 mg QD5.7
Percentage of Participants Who Achieve Response at Week 16 Secondary · Week 16

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 ass

GroupValue95% CI
Double-Blind Induction Phase: Placebo BID2.7
Double-Blind Induction Phase: Upadacitinib 3 mg BID15.4
Double-Blind Induction Phase: Upadacitinib 6 mg BID32.4
Double Blind Induction Phase: Upadacitinib 12 mg BID27.8
Double Blind Induction Phase: Upadacitinib 24 mg BID38.9
Double Blind Induction Phase: Upadacitinib 24 mg QD34.3
Percentage of Participants With Endoscopic Response at Week 12/16 Secondary · 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.)

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.

GroupValue95% CI
Double-Blind Induction Phase: Placebo BID13.5
Double-Blind Induction Phase: Upadacitinib 3 mg BID23.1
Double-Blind Induction Phase: Upadacitinib 6 mg BID43.2
Double Blind Induction Phase: Upadacitinib 12 mg BID36.1
Double Blind Induction Phase: Upadacitinib 24 mg BID50.0
Double Blind Induction Phase: Upadacitinib 24 mg QD48.6
Percentage of Participants Who Achieve Clinical Response at Week 16 Secondary · Week 16

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).

GroupValue95% CI
Double-Blind Induction Phase: Placebo BID32.4
Double-Blind Induction Phase: Upadacitinib 3 mg BID43.6
Double-Blind Induction Phase: Upadacitinib 6 mg BID56.8
Double Blind Induction Phase: Upadacitinib 12 mg BID47.2
Double Blind Induction Phase: Upadacitinib 24 mg BID61.1
Double Blind Induction Phase: Upadacitinib 24 mg QD48.6
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 Secondary · Week 16

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).

GroupValue95% CI
Double-Blind Induction Phase: Placebo BID7.1
Double-Blind Induction Phase: Upadacitinib 3 mg BID17.6
Double-Blind Induction Phase: Upadacitinib 6 mg BID18.8
Double Blind Induction Phase: Upadacitinib 12 mg BID16.7
Double Blind Induction Phase: Upadacitinib 24 mg BID25.0
Double Blind Induction Phase: Upadacitinib 24 mg QD11.1
Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve CDAI < 150 at Week 16 Secondary · Week 16

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.

GroupValue95% CI
Double-Blind Induction Phase: Placebo BID0.0
Double-Blind Induction Phase: Upadacitinib 3 mg BID19.0
Double-Blind Induction Phase: Upadacitinib 6 mg BID22.2
Double Blind Induction Phase: Upadacitinib 12 mg BID41.2
Double Blind Induction Phase: Upadacitinib 24 mg BID33.3
Double Blind Induction Phase: Upadacitinib 24 mg QD10.0
Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Remission at Week 12/16 and Clinical Remission at Week 16 Secondary · 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.)

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

GroupValue95% CI
Double-Blind Induction Phase: Placebo BID0.0
Double-Blind Induction Phase: Upadacitinib 3 mg BID0.0
Double-Blind Induction Phase: Upadacitinib 6 mg BID5.6
Double Blind Induction Phase: Upadacitinib 12 mg BID5.9
Double Blind Induction Phase: Upadacitinib 24 mg BID13.3
Double Blind Induction Phase: Upadacitinib 24 mg QD0.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment-emergent adverse events AEs (TEAEs): collected from the first dose of study drug through Week 52 plus 30 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Double-Blind Induction Phase: Placebo BID
Serious: 2/37 (5%)
Deaths: 0/37
Double-Blind Induction Phase: Upadacitinib 3 mg BID
Serious: 5/39 (13%)
Deaths: 0/39
Double-Blind Induction Phase: Upadacitinib 6 mg BID
Serious: 2/37 (5%)
Deaths: 0/37
Double Blind Induction Phase: 12 mg BID
Serious: 10/36 (28%)
Deaths: 0/36
Double Blind Induction Phase: 24 mg BID
Serious: 3/36 (8%)
Deaths: 0/36
Double Blind Induction Phase: 24 mg QD
Serious: 7/35 (20%)
Deaths: 0/35
Double Blind Extension Phase: 3 mg BID
Serious: 18/60 (30%)
Deaths: 0/60
Double Blind Extension Phase: 6 mg BID
Serious: 2/23 (9%)
Deaths: 0/23
Double Blind Extension 12 mg BID
Serious: 5/59 (8%)
Deaths: 0/59
Double Blind Extension 24 mg QD
Serious: 5/36 (14%)
Deaths: 0/36
Open Label Extension Subjects Never Received OL 24 mg BID
Serious: 11/33 (33%)
Deaths: 0/33
Open Label Extension Subjects Received OL 24 mg BID
Serious: 4/27 (15%)
Deaths: 0/27

Serious adverse events (53 terms)

ReactionSystemDouble-Blind Induction Pha…Double-Blind Induction Pha…Double-Blind Induction Pha…Double Blind Induction Pha…Double Blind Induction Pha…Double Blind Induction Pha…Double Blind Extension Pha…Double Blind Extension Pha…Double Blind Extension 12 …Double Blind Extension 24 …Open Label Extension Subje…Open Label Extension Subje…
CROHN'S DISEASEGastrointestinal disorders
ABDOMINAL PAINGastrointestinal disorders
SMALL INTESTINAL OBSTRUCTIONGastrointestinal disorders
ANAEMIABlood and lymphatic system disorders
ACUTE MYOCARDIAL INFARCTIONCardiac disorders
PULSELESS ELECTRICAL ACTIVITYCardiac disorders
SINUS BRADYCARDIACardiac disorders
SINUS TACHYCARDIACardiac disorders
VENTRICULAR TACHYCARDIACardiac disorders
ANAL FISTULAGastrointestinal disorders
ANAL HAEMORRHAGEGastrointestinal disorders
CONSTIPATIONGastrointestinal disorders
FISTULA OF SMALL INTESTINEGastrointestinal disorders
GASTROINTESTINAL OBSTRUCTIONGastrointestinal disorders
ILEAL PERFORATIONGastrointestinal disorders
ILEUSGastrointestinal disorders
INTESTINAL FISTULAGastrointestinal disorders
INTESTINAL OBSTRUCTIONGastrointestinal disorders
INTESTINAL STENOSISGastrointestinal disorders
IRRITABLE BOWEL SYNDROMEGastrointestinal disorders
MESENTERIC VEIN THROMBOSISGastrointestinal disorders
PERITONEAL ADHESIONSGastrointestinal disorders
SMALL INTESTINAL PERFORATIONGastrointestinal disorders
CHEST PAINGeneral disorders
ABDOMINAL ABSCESSInfections and infestations
Other adverse events (58 terms — click to expand)

ReactionSystemDouble-Blind Induction Pha…Double-Blind Induction Pha…Double-Blind Induction Pha…Double Blind Induction Pha…Double Blind Induction Pha…Double Blind Induction Pha…Double Blind Extension Pha…Double Blind Extension Pha…Double Blind Extension 12 …Double Blind Extension 24 …Open Label Extension Subje…Open Label Extension Subje…
FATIGUEGeneral disorders
HEADACHENervous system disorders
CROHN'S DISEASEGastrointestinal disorders
VIRAL UPPER RESPIRATORY TRACT INFECTIONInfections and infestations
ABDOMINAL PAINGastrointestinal disorders
PYREXIAGeneral disorders
URINARY TRACT INFECTIONInfections and infestations
ARTHRALGIAMusculoskeletal and connective tissue disorders
VOMITINGGastrointestinal disorders
ORAL HERPESInfections and infestations
UPPER RESPIRATORY TRACT INFECTIONInfections and infestations
BLOOD CREATINE PHOSPHOKINASE INCREASEDInvestigations
ACNESkin and subcutaneous tissue disorders
ANAEMIABlood and lymphatic system disorders
ABDOMINAL PAIN UPPERGastrointestinal disorders
DIARRHOEAGastrointestinal disorders
FLATULENCEGastrointestinal disorders
NAUSEAGastrointestinal disorders
PROCTALGIAGastrointestinal disorders
INFLUENZA LIKE ILLNESSGeneral disorders
BRONCHITISInfections and infestations
INFLUENZAInfections and infestations
PNEUMONIAInfections and infestations
C-REACTIVE PROTEIN INCREASEDInvestigations
COUGHRespiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAINRespiratory, thoracic and mediastinal disorders
RASHSkin and subcutaneous tissue disorders
LYMPHADENOPATHYBlood and lymphatic system disorders
EYE PAINEye disorders
ANORECTAL DISCOMFORTGastrointestinal disorders
CONSTIPATIONGastrointestinal disorders
DYSPEPSIAGastrointestinal disorders
GASTROOESOPHAGEAL REFLUX DISEASEGastrointestinal disorders
HAEMATOCHEZIAGastrointestinal disorders
INTESTINAL OBSTRUCTIONGastrointestinal disorders
CHILLSGeneral disorders
OEDEMA PERIPHERALGeneral disorders
GASTROENTERITISInfections and infestations
LOWER RESPIRATORY TRACT INFECTIONInfections and infestations
SINUSITISInfections and infestations

Most-reported serious reactions: CROHN'S DISEASE, ABDOMINAL PAIN, SMALL INTESTINAL OBSTRUCTION, ANAEMIA, ACUTE MYOCARDIAL INFARCTION, PULSELESS ELECTRICAL ACTIVITY, SINUS BRADYCARDIA, SINUS TACHYCARDIA.

Data from ClinicalTrials.gov NCT02365649 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases.
    Schwartz DM, Kanno Y, Villarino A, Ward M, et al · · 2017 · cited 308× · PMID 29282366 · DOI 10.1038/nrd.2017.267
  2. Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution.
    Bharadwaj U, Kasembeli MM, Robinson P, Tweardy DJ. · · 2020 · cited 242× · PMID 32198236 · DOI 10.1124/pr.119.018440
  3. Efficacy and Safety of Upadacitinib in a Randomized Trial of Patients With Crohn's Disease.
    Sandborn WJ, Feagan BG, Loftus EV, Peyrin-Biroulet L, et al · · 2020 · cited 230× · PMID 32044319 · DOI 10.1053/j.gastro.2020.01.047
  4. JAK-inhibitors. New players in the field of immune-mediated diseases, beyond rheumatoid arthritis.
    Fragoulis GE, McInnes IB, Siebert S. · · 2019 · cited 223× · PMID 30806709 · DOI 10.1093/rheumatology/key276
  5. Perspectives on Current and Novel Treatments for Inflammatory Bowel Disease.
    Na SY, Moon W. · · 2019 · cited 99× · PMID 31195433 · DOI 10.5009/gnl19019
  6. JAK-STAT signaling in human disease: From genetic syndromes to clinical inhibition.
    Luo Y, Alexander M, Gadina M, O'Shea JJ, et al · · 2021 · cited 92× · PMID 34625141 · DOI 10.1016/j.jaci.2021.08.004
  7. The Future of Janus Kinase Inhibitors in Inflammatory Bowel Disease.
    De Vries LCS, Wildenberg ME, De Jonge WJ, D'Haens GR. · · 2017 · cited 82× · PMID 28158411 · DOI 10.1093/ecco-jcc/jjx003
  8. JAK inhibitors: A new dawn for oral therapies in inflammatory bowel diseases.
    Herrera-deGuise C, Serra-Ruiz X, Lastiri E, Borruel N. · · 2023 · cited 65× · PMID 36936239 · DOI 10.3389/fmed.2023.1089099

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