Study Comparing Intravenous (IV)/Subcutaneous (SC) Risankizumab to IV/SC Ustekinumab to Assess Change in Crohn's Disease Activity Index (CDAI) in Adult Participants With Moderate to Severe Crohn's Disease (CD) (SEQUENCE)

• ClinicalTrials.gov Identifier: NCT04524611
• Recruitment Status: Active, not recruiting
• First Posted: August 24, 2020
• Last Update Posted: September 28, 2023
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: August 20, 2020
• First Posted Date: August 24, 2020
• Last Update Posted Date: September 28, 2023
• Actual Study Start Date: September 30, 2020
• Estimated Primary Completion Date: February 11, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 25, 2021)

• Percentage of Participants Achieving Clinical Remission at Week 24 [ Time Frame: Week 24 ]
  Clinical remission is defined as Crohn's disease activity index (CDAI)<150.
• Percentage of Participants Achieving Endoscopic Remission [ Time Frame: Week 48 ]
  Endoscopic remission is defined as Simple Endoscopic Score for Crohn's Disease (SES-CD) <= 4 and at least a 2-point reduction versus Baseline and no sub score greater than 1 in any individual variable, as scored by a central reviewer.
• Number of Participants Reporting Adverse Events [ Time Frame: Up to 220 Weeks ]
  An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.

Original Primary Outcome Measures (submitted: August 20, 2020)

• Percentage of Participants Achieving Clinical Remission (Non-Inferiority of Risankizumab vs Ustekinumab) [ Time Frame: Week 24 ]
  Clinical remission is defined as Crohn's disease activity index (CDAI)<150.
• Percentage of Participants Achieving Clinical Remission (Superiority of Risankizumab vs Ustekinumab) [ Time Frame: Week 48 ]
  Clinical remission is defined as Crohn's disease activity index (CDAI)<150.

Current Secondary Outcome Measures (submitted: October 25, 2021)

• Percentage of Participants Achieving Clinical Remission at Week 48 [ Time Frame: Week 48 ]
  Clinical remission is defined as Crohn's disease activity index (CDAI)<150.
• Percentage of Participants Achieving Endoscopic Response at Week 48 [ Time Frame: Week 48 ]
  Endoscopic response is defined as decrease in Simple Endoscopic Score for Crohn's Disease (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).
• Percentage of Participants Achieving Endoscopic Response at Week 24 [ Time Frame: Week 24 ]
  Endoscopic response is defined as decrease in Simple Endoscopic Score for Crohn's Disease (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).
• Percentage of Participants Achieving Steroid-Free Endoscopic Remission [ Time Frame: Week 48 ]
  Steroid-free endoscopic remission is defined as participants with endoscopic remission and not receiving steroids at Week 48.
• Percentage of Participants Achieving Steroid-Free Clinical Remission [ Time Frame: Week 48 ]
  Steroid-free clinical remission is defined as participants with clinical remission and not receiving steroids at Week 48.

Original Secondary Outcome Measures (submitted: August 20, 2020)

• Percentage of Participants Achieving Endoscopic Response (Superiority of Risankizumab vs Ustekinumab) [ Time Frame: Up to Week 48 ]
  Endoscopic response is defined as decrease in Simple Endoscopic Score for Crohn's Disease (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).
• Percentage of Participants Achieving Endoscopic Remission (Superiority of Risankizumab vs Ustekinumab) [ Time Frame: Week 48 ]
  Endoscopic remission is defined as decrease in SES-CD<=4 and at lease a 2-point reduction versus Baseline and no sub-score greater than 1 in any individual variable.
• Percentage of Participants Achieving Clinical Remission (Patient Reported Outcome [PRO]-2) (Superiority of Risankizumab vs Ustekinumab) [ Time Frame: Week 48 ]
  Clinical remission [PRO-2] is defined as 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.
• Percentage of Participants Achieving Steroid-Free Remission (Superiority of Risankizumab vs Ustekinumab) [ Time Frame: Week 48 ]
  Steroid-free remission is defined as discontinuation of corticosteroid use for 90 days and achieving clinical remission at Week 48 in participants taking steroids at Baseline.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Comparing Intravenous (IV)/Subcutaneous (SC) Risankizumab to IV/SC Ustekinumab to Assess Change in Crohn's Disease Activity Index (CDAI) in Adult Participants With Moderate to Severe Crohn's Disease (CD)
• Official Title: A Phase 3, Multicenter, Randomized, Efficacy Assessor-Blinded Study of Risankizumab Compared to Ustekinumab for the Treatment of Adult Subjects With Moderate to Severe Crohn's Disease Who Have Failed Anti-TNF Therapy

Brief Summary

Crohn's disease (CD) is a long-lasting condition causing inflammation that can affect any part of the gut. This study will evaluate how well risankizumab works compared to ustekinumab. This study will assess change in Crohn's Disease Activity Index (CDAI).

Risankizumab is an investigational drug being developed for the treatment of Crohn's Disease (CD). Ustekinumab is an approved drug for the treatment of moderate and severe CD. Participants are randomly assigned to one of the three treatment groups. Each group receives a different treatment. There is a 1 in 2 chance that participants will be assigned to ustekinumab. Around 508 adult participants with moderate to severe CD will be enrolled in approximately 307 sites worldwide.

In Part 1, participants assigned to risankizumab will receive intravenous (IV) doses of risankizumab at Week 0, 4,8 and subcutaneous (SC) doses every 8 weeks thereafter through Week 48. Participants assigned to ustekinumab will receive intravenous (IV) dose of ustekinumab at Week 0 and subcutaneous (SC) doses every 8 weeks thereafter through Week 48. In Part 2, participants who received risankizumab in Part 1 and completed the Week 48 visit will continue to receive SC risankizumab for up to an additional 220 weeks.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Crohn's Disease (CD)

Intervention

• Drug: Risankizumab
  Intravenous (IV) Infusion
  Other Names:

  • ABBV-066
  • SKYRIZI
• Drug: Risankizumab
  Subcutaneous (SC) Injection
  Other Names:

  • ABBV-066
  • SKYRIZI
• Drug: Ustekinumab
  Intravenous (IV) infusion
• Drug: Ustekinumab
  Subcutaneous (SC) injection

Study Arms

• Experimental: Risankizumab Dose A Followed by Dose B
  Participants will receive intravenous risankizumab dose A at Week 0, 4 ,8 followed by subcutaneous (SC) risankizumab dose B every 8 weeks through Week 48. Participants who complete the Week 48 visit will continue SC risankizumab for up to an additional 220 weeks.
  Interventions:

  • Drug: Risankizumab
  • Drug: Risankizumab
• Active Comparator: Ustekinumab
  Participants will receive weight-based intravenous ustekinumab at Week 0 followed by subcutaneous ustekinumab every 8 weeks through Week 48.
  Interventions:

  • Drug: Ustekinumab
  • Drug: Ustekinumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 24, 2022): 527
• Original Estimated Enrollment (submitted: August 20, 2020): 508
• Estimated Study Completion Date: February 11, 2028
• Estimated Primary Completion Date: February 11, 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Confirmed diagnosis of Crohn's disease (CD) for at least 3 months prior to Baseline.
• Crohn's disease activity index (CDAI) score 220 - 450 at Baseline.
• Confirmed diagnosis of moderate to severe Crohn's Disease as assessed by stool frequency (SF), abdominal pain (AP) score, and Simple Endoscopic score for CD (SES-CD).
• Demonstrated intolerance or inadequate response to one or more anti-tumor necrosis factor (TNF) therapies.

Exclusion Criteria:

• Current diagnosis of ulcerative colitis or indeterminate colitis.
• Receipt of CD approved biologic agents prior to Baseline (as detailed in protocol), or any investigational biologic or other agent or procedure prior to Baseline (as detailed in protocol).
• Prior exposure to p19 and/or p40 inhibitors (e.g., risankizumab and ustekinumab).
• Currently know complications of CD (strictures, short bowel, etc).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Mexico, Netherlands, Poland, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT04524611
• Other Study ID Numbers: M20-259; 2020-002674-26 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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.: Yes

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, analyses plans, 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
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• 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 and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• URL: https://vivli.org/ourmember/abbvie/

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: ABBVIE INC.; AbbVie

• PRS Account: AbbVie
• Verification Date: September 2023