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NCT03105128

A Study of the Efficacy and Safety of Risankizumab in Participants With Moderately to Severely Active Crohn's Disease

Completed Phase 3 Results posted Last updated 6 July 2022
What this trial tests

Phase 3 trial testing placebo for risankizumab in Crohn's Disease in 931 participants. Completed in 14 April 2021.

Timeline
10 May 2017
Primary endpoint
9 November 2020
14 April 2021

Quick facts

Lead sponsorAbbVie
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment931
Start date10 May 2017
Primary completion9 November 2020
Estimated completion14 April 2021
Sites475 locations across Hong Kong, Colombia, Italy, Japan, Malaysia, Ireland, Poland, South Korea

Drugs / interventions tested

Conditions studied

Sponsor

AbbVie — full company profile →

Who can join

Adults 16 to 80, 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.

US Specific: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission Primary · Week 12

The CDAI consists of 8 components; 7 are based on participant diary entries, participant interviews, physical examinations, measurement of body weight and height and 1 is based on laboratory analysis. CDAI clinical remission of Crohn's disease is defined as CDAI \< 150.

GroupValue95% CI
Placebo (Period 1)24.618.2 – 31.0
Risankizumab 600mg (Period 1)45.239.9 – 50.5
Risankizumab 1200mg (Period 1)41.636.3 – 46.8
US Specific: Percentage of Participants With Endoscopic Response Primary · Week 12

The SES-CD assesses endoscopic disease severity by evidence of active intestinal mucosal inflammation. Endoscopic response is defined as a decrease in SES-CD \> 50% from Baseline (or for participants with isolated ileal disease and a Baseline SES-CD of 4, at least a 2-point reduction from Baseline).

GroupValue95% CI
Placebo (Period 1)12.07.2 – 16.8
Risankizumab 600mg (Period 1)40.335.0 – 45.6
Risankizumab 1200mg (Period 1)32.127.1 – 37.1
Global Outside of US: Percentage of Participants With Clinical Remission Primary · Week 12

Clinical remission is defined as using the average daily Stool Frequency (SF) ≤ 2.8 and not worse than Baseline AND average daily Abdominal Pain (AP) score ≤ 1 and not worse than Baseline.

GroupValue95% CI
Placebo (Period 1)21.715.6 – 27.8
Risankizumab 600mg (Period 1)43.538.2 – 48.8
Risankizumab 1200mg (Period 1)41.035.8 – 46.2
Global Outside of US: Percentage of Participants With Endoscopic Response Primary · Week 12

The SES-CD assesses endoscopic disease severity by evidence of active intestinal mucosal inflammation. Endoscopic response is defined as a decrease in SES-CD \> 50% from Baseline (or for participants with isolated ileal disease and a Baseline SES-CD of 4, at least a 2-point reduction from Baseline).

GroupValue95% CI
Placebo (Period 1)12.07.2 – 16.8
Risankizumab 600mg (Period 1)40.335.0 – 45.6
Risankizumab 1200mg (Period 1)32.127.1 – 37.1
US Specific: Percentage of Participants With Clinical Remission Secondary · Week 12

Clinical remission is defined as using the average daily Stool Frequency (SF) ≤ 2.8 and not worse than Baseline AND average daily Abdominal Pain (AP) score ≤ 1 and not worse than Baseline.

GroupValue95% CI
Placebo (Period 1)21.715.6 – 27.8
Risankizumab 600mg (Period 1)43.538.2 – 48.8
Risankizumab 1200mg (Period 1)41.035.8 – 46.2
US Specific: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Response Secondary · Week 4

Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Higher CDAI scores indicate more severe disease. CDAI clinical response is defined as reduction of CDAI ≥ 100 points from baseline.

GroupValue95% CI
Placebo (Period 1)25.218.7 – 31.6
Risankizumab 600mg (Period 1)40.835.5 – 46.0
Risankizumab 1200mg (Period 1)37.232.0 – 42.3
US Specific: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Response Secondary · Week 12

Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Higher CDAI scores indicate more severe disease. CDAI clinical response is defined as reduction of CDAI ≥ 100 points from baseline.

GroupValue95% CI
Placebo (Period 1)36.729.6 – 43.9
Risankizumab 600mg (Period 1)59.754.5 – 65.0
Risankizumab 1200mg (Period 1)64.959.8 – 70.0
US Specific: Change From Baseline of Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Secondary · Week 12

The FACIT-Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four point Likert scale. The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. A positive change from baseline indicates improvement.

GroupValue95% CI
Placebo (Period 1)6.04.4 – 7.7
Risankizumab 600mg (Period 1)11.210.1 – 12.4
Risankizumab 1200mg (Period 1)10.19.0 – 11.3
US Specific: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission Secondary · Week 4

Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Higher CDAI scores indicate more severe disease. CDAI clinical remission of Crohn's disease is defined as CDAI \< 150.

GroupValue95% CI
Placebo (Period 1)10.35.8 – 14.8
Risankizumab 600mg (Period 1)18.414.3 – 22.6
Risankizumab 1200mg (Period 1)18.914.7 – 23.0
US Specific: Percentage of Participants With CDAI Clinical Response and Endoscopic Response Secondary · Week 12

Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Higher CDAI scores indicate more severe disease. CDAI clinical response is defined as reduction of CDAI ≥ 100 points from baseline. Endoscopic response was a decrease in Simplified Endoscopic Score for Crohn's Disease (SES-CD) \> 50% from Baseline (or for subjects with isolated ileal disease and a Baseline SES-CD of 4, at least a 2 point reduction from Baseline).

GroupValue95% CI
Placebo (Period 1)5.72.3 – 9.2
Risankizumab 600mg (Period 1)30.025.1 – 34.9
Risankizumab 1200mg (Period 1)23.018.5 – 27.5
US Specific: Percentage of Participants With Stool Frequency (SF) Remission Secondary · Week 12

Stool Frequency (SF) remission is defined as an average daily SF \<= 2.8 and not worse than baseline.

GroupValue95% CI
Placebo (Period 1)29.823.1 – 36.6
Risankizumab 600mg (Period 1)54.248.8 – 59.5
Risankizumab 1200mg (Period 1)54.048.7 – 59.3
US Specific: Percentage of Participants With Abdominal Pain (AP) Remission Secondary · Week 12

The Abdominal Pain rating is an assessment that is graded from 0 to 3: 0= None, 1= Mild, 2= Moderate and 3= Severe. AP remission is defined as average daily AP score \<= 1 and not worse than baseline.

GroupValue95% CI
Placebo (Period 1)38.531.2 – 45.7
Risankizumab 600mg (Period 1)59.654.3 – 64.8
Risankizumab 1200mg (Period 1)58.152.9 – 63.4

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment-emergent AEs (TEAEs) are from first dose of study drug until 140 days following last dose of study drug. The median duration of treatment for Period 1 with study drug for placebo and Risankizumab was 91.5 and 91 days respectively. For Period 2, the median duration of treatment with study drug for Risankizumab was 141 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Period 1 Placebo IV
Serious: 28/186 (15%)
Deaths: 2/186
Period 1 Risankizumab 600mg IV
Serious: 27/373 (7%)
Deaths: 0/373
Period 1 Risankizumab 1200mg IV
Serious: 14/372 (4%)
Deaths: 0/372
Period 1 Risankizumab Total
Serious: 41/745 (6%)
Deaths: 0/745
Period 2 Risankizumab 180mg SC
Serious: 3/67 (4%)
Deaths: 0/67
Period 2 Risankizumab 360mg SC
Serious: 3/68 (4%)
Deaths: 0/68
Period 2 Risankizumab 1200mg IV
Serious: 4/67 (6%)
Deaths: 0/67
Period 2 Placebo/Risankizumab 1200mg IV
Serious: 4/76 (5%)
Deaths: 0/76
Period 2 Risankizumab Total
Serious: 14/278 (5%)
Deaths: 0/278

Serious adverse events (71 terms)

ReactionSystemPeriod 1 Placebo IVPeriod 1 Risankizumab 600m…Period 1 Risankizumab 1200…Period 1 Risankizumab TotalPeriod 2 Risankizumab 180m…Period 2 Risankizumab 360m…Period 2 Risankizumab 1200…Period 2 Placebo/Risankizu…Period 2 Risankizumab Total
CROHN'S DISEASEGastrointestinal disorders
INTESTINAL OBSTRUCTIONGastrointestinal disorders
ABDOMINAL PAINGastrointestinal disorders
ILEUSGastrointestinal disorders
INTESTINAL STENOSISGastrointestinal disorders
LARGE INTESTINE PERFORATIONGastrointestinal disorders
SMALL INTESTINAL OBSTRUCTIONGastrointestinal disorders
URETEROLITHIASISRenal and urinary disorders
ANAEMIABlood and lymphatic system disorders
VENTRICULAR TACHYCARDIACardiac disorders
RETINAL DISORDEREye disorders
ABDOMINAL HERNIAGastrointestinal disorders
COLITISGastrointestinal disorders
DIARRHOEAGastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGEGastrointestinal disorders
GASTROINTESTINAL INFLAMMATIONGastrointestinal disorders
GASTROINTESTINAL NECROSISGastrointestinal disorders
ILEAL PERFORATIONGastrointestinal disorders
ILEAL STENOSISGastrointestinal disorders
INTESTINAL ISCHAEMIAGastrointestinal disorders
NAUSEAGastrointestinal disorders
PANCREATITIS ACUTEGastrointestinal disorders
SUBILEUSGastrointestinal disorders
TERMINAL ILEITISGastrointestinal disorders
VOMITINGGastrointestinal disorders
Other adverse events (5 terms — click to expand)

ReactionSystemPeriod 1 Placebo IVPeriod 1 Risankizumab 600m…Period 1 Risankizumab 1200…Period 1 Risankizumab TotalPeriod 2 Risankizumab 180m…Period 2 Risankizumab 360m…Period 2 Risankizumab 1200…Period 2 Placebo/Risankizu…Period 2 Risankizumab Total
NASOPHARYNGITISInfections and infestations
HEADACHENervous system disorders
NAUSEAGastrointestinal disorders
ANAEMIABlood and lymphatic system disorders
CROHN'S DISEASEGastrointestinal disorders

Most-reported serious reactions: CROHN'S DISEASE, INTESTINAL OBSTRUCTION, ABDOMINAL PAIN, ILEUS, INTESTINAL STENOSIS, LARGE INTESTINE PERFORATION, SMALL INTESTINAL OBSTRUCTION, URETEROLITHIASIS.

Data from ClinicalTrials.gov NCT03105128 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the efficacy and safety of risankizumab versus placebo during induction therapy in participants with moderately to severely active Crohn's disease (CD).

Publications & conference data

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

  1. Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials.
    D'Haens G, Panaccione R, Baert F, Bossuyt P, et al · · 2022 · cited 290× · PMID 35644154 · DOI 10.1016/s0140-6736(22)00467-6
  2. Novel and Emerging Therapies for Inflammatory Bowel Disease.
    Al-Bawardy B, Shivashankar R, Proctor DD. · · 2021 · cited 117× · PMID 33935763 · DOI 10.3389/fphar.2021.651415
  3. Targeted Immunotherapy for Autoimmune Disease.
    Jung SM, Kim WU. · · 2022 · cited 113× · PMID 35291650 · DOI 10.4110/in.2022.22.e9
  4. The role of inflammation in autoimmune disease: a therapeutic target.
    Xiang Y, Zhang M, Jiang D, Su Q, et al · · 2023 · cited 104× · PMID 37859999 · DOI 10.3389/fimmu.2023.1267091
  5. Interleukin 23 in the skin: role in psoriasis pathogenesis and selective interleukin 23 blockade as treatment.
    Chan TC, Hawkes JE, Krueger JG. · · 2018 · cited 103× · PMID 29796240 · DOI 10.1177/2040622318759282
  6. Perspectives on Current and Novel Treatments for Inflammatory Bowel Disease.
    Na SY, Moon W. · · 2019 · cited 99× · PMID 31195433 · DOI 10.5009/gnl19019
  7. Interleukin-23 in the Pathogenesis of Inflammatory Bowel Disease and Implications for Therapeutic Intervention.
    Sewell GW, Kaser A. · · 2022 · cited 89× · PMID 35553667 · DOI 10.1093/ecco-jcc/jjac034
  8. A State-of-the-Art Review of New and Emerging Therapies for the Treatment of IBD.
    Chudy-Onwugaje KO, Christian KE, Farraye FA, Cross RK. · · 2019 · cited 87× · PMID 30445504 · DOI 10.1093/ibd/izy327

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