A Study to Investigate How Well Ravagalimab (ABBV-323) Works and How Safe it is in Participants With Moderate to Severe Ulcerative Colitis Who Failed Prior Therapy

A Multicenter, Single Arm, Open-label Study to Investigate the Efficacy and Safety of Ravagalimab (ABBV-323) in Subjects With Moderate to Severe Ulcerative Colitis Who Failed Prior Therapy

Study M15-722 is a Phase 2a study to investigate the efficacy and safety of Ravagalimab (ABBV-323) in participants with moderate to severe UC who failed prior therapy.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis (UC)
• Intervention / Treatment: Drug: Ravagalimab 600 mg; Drug: Ravagalimab 300 mg

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital /ID# 206180
• France
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 06200
      • Chu de Nice-Hopital L'Archet Ii /Id# 208131
  • Ile-de-France
    • Clichy, Ile-de-France, France, 92110
      • Hopital Beaujon /ID# 208129
  • Meurthe-et-Moselle
    • Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France, 54500
      • CHRU Nancy - Hôpitaux de Brabois /ID# 208133
• Germany
  • Berlin, Germany, 10117
    • Charite Universitaetsmedizin Berlin - Campus Mitte /ID# 207570
  • Hessen
    • Frankfurt am Main, Hessen, Germany, 60590
      • Universitaetsklinikum Frankfurt /ID# 207569
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Universitaetsklinikum Schleswig-Holstein Campus Kiel /ID# 207571
• Hungary
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont /ID# 221952
  • Csongrad
    • Szeged, Csongrad, Hungary, 6725
      • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont /ID# 221576
• Italy
  • Milan, Italy, 20122
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 208504
  • Calabria
    • Catanzaro, Calabria, Italy, 88100
      • University of Catanzaro /ID# 204546
  • Roma
    • Rome, Roma, Italy, 00168
      • Presidio Columbus-Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Un /ID# 204549
• Korea, Republic of
  • Daegu, Korea, Republic of, 41944
    • Kyungpook National University Hospital /ID# 209912
  • Daegu, Korea, Republic of, 42415
    • Yeungnam University Medical Center /ID# 210447
• Netherlands
  • Maastricht, Netherlands, 6229 HX
    • Maastricht Universitair Medisch Centrum /ID# 204428
  • Rotterdam, Netherlands, 3045 PM
    • Franciscus Gasthuis & Vlietland /ID# 206976
  • Tilburg, Netherlands, 5022 GC
    • Elisabeth Tweesteden Ziekenhuis /ID# 206272
• Spain
  • Barcelona, Spain, 08041
    • Hospital Santa Creu i Sant Pau /ID# 213259
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon /ID# 204504
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz /ID# 210065
• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Belfast Health and Social Care Trust /ID# 206744
  • Scotland
    • Glasgow, Scotland, United Kingdom, G12 0XH
      • NHS Greater Glasgow and Clyde /ID# 206574
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Banner University Medical Cent /ID# 208392
  • California
    • Huntington Beach, California, United States, 92648-5994
      • Meridian Investigator Network /ID# 204646
    • Lakewood, California, United States, 90712
      • Meridian Investigator Network /ID# 218568
    • Los Angeles, California, United States, 90048
      • TLC Clinical Research Inc /ID# 206626
    • Mission Viejo, California, United States, 92691-6306
      • Orange County Institute of Gastroenterology and Endoscopy /ID# 207405
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center /ID# 209402
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago DCAM /ID# 207086
    • Oak Brook, Illinois, United States, 60523-1245
      • Affinity Clinical Research /ID# 206211
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • Univ New Mexico /ID# 208817
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-2640
      • Penn Presbyterian Medical Center /ID# 206826
  • Tennessee
    • Nashville, Tennessee, United States, 37232-0011
      • Vanderbilt University Medical Center /ID# 204670
  • Texas
    • San Antonio, Texas, United States, 78212
      • Clinical Associates in Research Therapeutics of America, LLC /ID# 204689

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants must voluntarily sign and date an informed consent, approved by an independent ethics committee (IEC)/institutional review board (IRB), prior to the initiation of any screening or study-specific procedures.
• Diagnosis of UC for at least 3 months prior to Baseline. Appropriate documentation of biopsy results consistent with the diagnosis of UC in the assessment of the Investigator, must be available.
• Participant meets the following disease activity criteria: Active UC with an Adapted Mayo score of 5 to 9 points and endoscopic subscore of 2 to 3 (confirmed by central review).
• History of inadequate response, loss of response, or intolerance to one or more of the approved biologic therapies: infliximab, adalimumab, golimumab, vedolizumab, and/or tofacitinib (Note: If tofacitinib was received in a clinical trial, subject must have received open-label drug).

Exclusion Criteria:

• Participant having an active, chronic, or recurrent infection that based on Investigator's clinical assessment makes the participant an unsuitable candidate for the study.
• Participant having any malignancy except for successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix.
• Participant with history of dysplasia of the gastrointestinal tract or evidence of dysplasia in any biopsy performed during the screening endoscopy other than completely removed low-grade dysplastic lesions.
• Laboratory values not meeting the following criteria : Serum aspartate transaminase (AST) and alanine transaminase (ALT) <= 2* upper limit of normal (ULN); Total white blood cell (WBC) count >= 3.0*10^9/L.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ravagalimab 600 mg/300 mg; Participants received ravagalimab 600 mg intravenous (IV) at Week 0 followed by ravagalimab 300 mg subcutaneously (SC) at Weeks 2, 4, 6, 8, and 10 in a 12-week Induction Period. Participants who achieved clinical response per partial adapted Mayo score at Week 12 of the Induction Period entered the Maintenance Period to receive ravagalimab 300 mg SC every other week (EOW) from Week 12 through Week 102.

Drug: Ravagalimab 600 mg; Ravagalimab 600 mg was administered intravenously (IV).; Other Names: ABBV-323; Drug: Ravagalimab 300 mg; Ravagalimab 300 mg was administered subcutaneously (SC).; Other Names: ABBV-323

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Endoscopic Improvement During Induction Period	Endoscopic Improvement is defined as Mayo endoscopic subscore of 0 or 1. Mayo endoscopic score is classified as 0=Normal or inactive disease; 1=Mild disease (erythema, decreased vascular pattern); 2=Moderate disease (marked erythema, absent vascular pattern, friability, erosions); 3=Severe disease (spontaneous bleeding, ulceration). Higher score indicates worsening of the disease. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to a nearest whole integer.	At Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Clinical Remission Per Adapted Mayo Score During Induction Period	Clinical remission per Adapted Mayo score is defined as stool frequency subscore (SFS) <=1, and not greater than baseline, rectal bleeding subscore (RBS) = 0, and endoscopic subscore <=1. The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal), Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed), Endoscopic subscore confirmed by central reader, 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. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to a nearest whole integer.	At Week 8
Percentage of Participants With Clinical Response Per Adapted Mayo Score During Induction Period	Clinical response per Adapted Mayo score is defined as the decrease from Baseline >= 2 points and >= 30%, PLUS a decrease in RBS >=1 or an absolute RBS <=1. The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal), Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed), 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 with higher scores representing more severe disease. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to a nearest whole integer.	At Week 8
Percentage of Participants With Clinical Response Per Partial Adapted Mayo Score	Clinical response per Partial Adapted Mayo score is defined as decrease from baseline >=1 points and >=30%, PLUS a decrease in RBS >= 1 or an absolute RBS <=1. The Partial Adapted Mayo Score is a composite score of UC disease activity based on the following 2 subscores: SFS, scored from 0 (normal number of stools) to 3 (5 or more stools more than normal); RBS, scored from 0 (no blood seen) to 3 (blood alone passed). The overall Partial Adapted Mayo score ranges from 0 to 6 with higher scores representing more severe disease. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to a nearest whole integer.	Up to Week 8
Percentage of Participants With Clinical Remission Per Full Mayo Score During Induction Period in Participants With a Full Mayo Score of 6 to 12 at Baseline	Clinical Remission per full Mayo score is defined as Full Mayo score <=2 with no subscore > 1. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The 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). Endoscopies were assessed by a central reader. Negative changes indicate improvement. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to the nearest whole integer.	At Week 8
Percentage of Participants With Endoscopic Remission During Induction Period	Endoscopic remission is defined as Mayo endoscopic subscore = 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). Higher score indicates worsening of the disease. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to the nearest whole integer.	At Week 8

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2019
• Primary Completion (Actual): April 5, 2021
• Study Completion (Actual): January 10, 2022

Study Registration Dates

• First Submitted: October 2, 2018
• First Submitted That Met QC Criteria: October 2, 2018
• First Posted (Actual): October 4, 2018

Study Record Updates

• Last Update Posted (Actual): March 15, 2023
• Last Update Submitted That Met QC Criteria: February 16, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Ulcerative Colitis (UC); Ravagalimab; ABBV-323
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: M15-722; 2018-000930-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing 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/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• 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