A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of UTTR1147A Compared With Placebo and With Vedolizumab in Participants With Moderate to Severe Ulcerative Colitis (UC)

A Phase II, Randomized, Parallel-Group, Double-Blind, Double-Dummy, Placebo-Controlled, Multicenter Study To Evaluate the Efficacy, Safety, and Pharmacokinetics of UTTR1147A Compared With Placebo and Compared With Vedolizumab in Patients With Moderate to Severe Ulcerative Colitis

This study is designed to evaluate the efficacy, safety, and pharmacokinetics of UTTR1147A compared with vedolizumab and with placebo in the treatment of participants with moderate to severe UC. This study will consist of two parts, Part A and Part B. Part A will test the induction of clinical remission and Part B will test the durability of clinical remission.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: UTTR1147A; Drug: Vedolizumab Placebo; Drug: UTTR1147A Placebo; Drug: Vedolizumab

• Study Type: Interventional
• Enrollment (Actual): 195
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • MHAT Saint Karidad EAD
  • Sliven, Bulgaria, 8800
    • Multiprofile Hospital for Active Treatment Hadji Dimitar OOD
• Georgia
  • Tbilisi, Georgia, 0112
    • LLC Arensia Exploratory Medicine
• Germany
  • Berlin, Germany, 10318
    • Gastroenterologische Spezialpraxis-Berlin-Karlshorst
  • Dresden, Germany, 01307
    • Universitaetsklinikum Carl Gustav Carus TU Dresden
  • Lubeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein
  • Ludwigshafen, Germany, 67067
    • St. Marien Krankenhaus; Med. Klinik
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm; Klinik für Innere Medizin II
• Greece
  • Palaio Faliro, Greece, 175 62
    • Iatriko Palaiou Falirou; Gastrointestinal Department
  • Thessaloniki, Greece, 54645
    • EUROMEDICA General Clinic of Thessaloniki; Gastroenterology Department
• Hungary
  • Budapest, Hungary, 1134
    • Magyar Honvédség Egészségügyi Központ; Országos Haemophilia Központ
• Ireland
  • Co Galway, Ireland
    • Portiuncula Hospital, Ballinasloe
• Israel
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center; Bait Vagan
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00128
      • Policlinico Universitario Campus Biomedico Di Roma
    • Roma, Lazio, Italy, 00168
      • Complesso Integrato Columbus
  • Lombardia
    • Monza, Lombardia, Italy, 20900
      • ASST di Monza - Azienda Ospedaliera San Gerardo; U.O. Farmacia -Settore A - Corpo Posteriore
    • Rozzano (MI), Lombardia, Italy, 20089
      • Istituto Clinico Humanitas
  • Veneto
    • Padova, Veneto, Italy, 35128
      • Azienda Ospedaliera di Padova
• Moldova, Republic of
  • Chisinau, Moldova, Republic of, MD-2025
    • ICS ARENSIA Exploratory Medicine
• Poland
  • ?ód?, Poland, 90-153
    • SPZOZ Uniwersytecki SK nr 1 im N. Barlickiego UM w Lodzi; Oddz. Klin. Gastroenter. Og. i Onk.
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy; Centrum Endoskopii Zabiegowej
  • Cz?stochowa, Poland, 42-202
    • Synexus Polska Sp. z o.o. Oddzial w Czestochowie
  • Gda?sk, Poland, 80-382
    • Synexus Polska Sp. z o.o. Oddzial w Gdansku
  • Katowice, Poland, 40-040
    • Synexus - Katowice
  • Katowice, Poland, 40-660
    • Economicus - NZOZ ALL-MEDICUS; Zaklad Gastroenterologii
  • Kielce, Poland, 25-355
    • ETG Kielce
  • Lublin, Poland, 20-582
    • Gastromed SPK Niepubliczny Zaklad Opieki Zdrowotnej
  • Piotrków Trybunalski, Poland, 97-300
    • KLIMED Marek Klimkiewicz
  • Pozna?, Poland, 60-702
    • Synexus Polska Sp. z o.o. Oddzial w Poznaniu
  • Pozna?, Poland, 61-731
    • Clinical Research Center Sp. z o.o. MEDIC-R Spó?ka Komandytowa
  • Sopot, Poland, 81-756
    • ENDOSKOPIA Sp. z o.o.
  • Toru?, Poland, 87-100
    • Gastromed Kopon Zmudzinski i
  • Warszawa, Poland, 00-635
    • Centrum Zdrowia MDM
  • Warszawa, Poland, 00-728
    • Jaroslaw Kierkus Prywatna Prakyka Lekarska
  • Wroc?aw, Poland, 50-220
    • Przychodnia EuroMediCare
  • Wroc?aw, Poland, 50-381
    • Synexus Polska Sp. z o.o. Oddzial we Wroclawiu
  • Wroc?aw, Poland, 50-449
    • Melita Medical
• Russian Federation
  • Irkutsk, Russian Federation, 664033
    • Irkutsk Research Centre Hospital of Siberian department of Russian Academy of Science
  • Rostov-na-Donu, Russian Federation, 344022
    • Rostov State Medical University; Cardiorheumatology Department
  • Samara, Russian Federation, 443011
    • Medical University Reaviz
  • St. Petersburg, Russian Federation, 191015
    • North-West State Medical University n.a. I.I. Mechnikov
  • Sankt Petersburg
    • Sankt-peterburg, Sankt Petersburg, Russian Federation, 195257
      • Saint Martyr Elizabeth City Hospital
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center Zvezdara
  • Belgrade, Serbia, 11000
    • KBC Dr Dragisa Misovic Dedinje
  • Belgrade, Serbia, 11080
    • University Hospital Medical Center Bezanijska kosa
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac; Clinic Of Psychiatry
  • Vrsac, Serbia, 26300
    • General Hospital Vrsac
  • Zemun, Serbia, 11080
    • Clinical Hospital Centre Zemun
  • Zrenjanin, Serbia, 23000
    • General Hospital Djordje Joanovic - Zrenjanin
• Spain
  • LAS Palmas
    • Las Palmas de Gran Canaria, LAS Palmas, Spain, 35010
      • Hospital de Gran Canaria Dr. Negrin; Servicio de Aparato Digestivo
  • Madrid
    • Torrejon de Ardoz, Madrid, Spain, 28850
      • Hospital Universitario de Torrejon
• Ukraine
  • Uzhgorod, Ukraine, 88000
    • Transcarpathian Regional Clinical Hospital n.a. A. Novak; Rheumatology Department
  • Zaporizhzhia, Ukraine, 69035
    • Medical Center of Diaservice LLC; Division of clinical trials conduct, Department #3
  • Chernihiv Governorate
    • Chernivtsi, Chernihiv Governorate, Ukraine, 58001
      • Regional Municipal Institution Chernivtsi Regional Clinical Hospital; Gastroenterology department
  • Crimean Regional Governmenta
    • Zhytomir, Crimean Regional Governmenta, Ukraine, 10008
      • Medical Centre of PE First Private Clinic
  • KIEV Governorate
    • Dnipro, KIEV Governorate, Ukraine, 49005
      • ME Dnipropetrovsk Regional Clinical Hospital n.a. I.I Mechnykov Dnipropetrovsk Regional Council
    • Kropyvnytskyi, KIEV Governorate, Ukraine, 25005
      • Treatment and Diagnostic Center of LLC MRT Elit
    • Kyiv, KIEV Governorate, Ukraine, 2091
      • Med Center of International Institute of Clinical Trials LLC; Medical Center "OK!Clinic+"
    • Kyiv, KIEV Governorate, Ukraine, 01001
      • Medical Center of LLC Medical Clinic Blagomed
    • Kyiv, KIEV Governorate, Ukraine, 02000
      • Medical Center of LLC Medical Center Dopomoga Plus
    • Kyiv, KIEV Governorate, Ukraine, 02002
      • Medical Center of Edelweiss Medics LLC
    • Kyiv, KIEV Governorate, Ukraine, 03037
      • Synexus Affiliate - MC of LLC Medbud-Clinic
    • Kyiv, KIEV Governorate, Ukraine, 01135
      • Medical Center of Limited Liability Company ?Harmoniya krasy?
    • Zaporizhzhia, KIEV Governorate, Ukraine, 69076
      • Medical Center of LLC Diaservis
  • Katerynoslav Governorate
    • Ternopil, Katerynoslav Governorate, Ukraine, 46002
      • Ternopil University Hospital; Regional Center of Gastroenterology with Hepatology
  • Kharkiv Governorate
    • Vinnytsia, Kharkiv Governorate, Ukraine, 21029
      • City Clinical Hospital #1; Department of Gastroenterology
    • Zaporizhzhia, Kharkiv Governorate, Ukraine, 69600
      • Municipal Institution Zaporizhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council
  • Podolia Governorate
    • Vinnytsia, Podolia Governorate, Ukraine, 21029
      • Clinic of SRI of Invalid Rehab. (ESTC) of VNMU n.a. M.I.Pyrohov
  • Polissya Okruha
    • Dnipr, Polissya Okruha, Ukraine, 49600
      • Medical Center of LLC Medical Center Family Medicine Clinic; Endoscopy & Gastroenterology
• United Kingdom
  • London, United Kingdom, SW9 8RR
    • Kings College Hospital
• United States
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Carolina Digestive Diseases
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah School of Medicine; Gastroenterology Division

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of UC
• Confirmation of moderately to severely active UC, defined by the Mayo Clinic Score
• Inadequate response, loss of response, or intolerance to prior immunosuppressant treatment (i.e., azathioprine, 6-mercaptopurine, methotrexate, or tumor necrosis factor [TNF] inhibitors [maximum of 2 prior TNF inhibitors]) and/or corticosteroid treatment
• Use of highly effective contraception as defined by the protocol

Exclusion Criteria:

• History of psoriasis or psoriatic arthritis; any other inflammatory skin disorders requiring oral corticosteroids, immunosuppressants, or biological therapy within the previous year; or primary sclerosing cholangitis
• History of cancer as defined by the protocol
• Significant uncontrolled comorbidity, such as cardiac, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders (excluding UC)
• Prior extensive colonic resection, subtotal or total colectomy, or proctocolectomy, or planned surgery for UC
• Diagnosis of indeterminate colitis or granulomatous (Crohn's) colitis or toxic megacolon within 12 months prior to screening
• Suspicion of ischemic colitis, radiation colitis, or microscopic colitis
• Current fistula or history of fistula, pericolonic abscess and stricture (stenosis) of the colon
• History or current evidence of unresectable colonic mucosal dysplasia or history of high-grade colonic mucosal dysplasia
• Prior treatment with UTTR1147A
• Prior treatment with vedolizumab, etrolizumab, natalizumab, efalizumab, or any other anti-integrin agents
• Prior treatment with rituximab
• Use of prohibited therapies, as defined by the protocol, prior to randomization
• Congenital or acquired immune deficiency
• Evidence or treatment of infections or history of infections, as defined by the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1a: UTTR1147A Dose Level 1 (Part A) + UTTR1147A (Part B); Part A: UTTR1147A dose level 1 and Vedolizumab Placebo. Part B: UTTR1147A maintenance dose and Vedolizumab Placebo.	Drug: UTTR1147A; UTTR1147A will be administered intravenously (IV) at dose levels 1, 2, or 3 in Part A, and at the maintenance dose level in Part B, per the respective arm descriptions.; Other Names: RG7880; RO7021610; IL-22Fc; Efmarodocokin alfa; Drug: Vedolizumab Placebo; The matching placebo to vedolizumab (Vedolizumab Placebo) will be administered IV.
Experimental: Arm 1b: UTTR1147A Dose Level 1 (Part A) + Placebo (Part B); Part A: UTTR1147A dose level 1 and Vedolizumab Placebo. Part B: UTTR1147A Placebo and Vedolizumab Placebo.	Drug: UTTR1147A; UTTR1147A will be administered intravenously (IV) at dose levels 1, 2, or 3 in Part A, and at the maintenance dose level in Part B, per the respective arm descriptions.; Other Names: RG7880; RO7021610; IL-22Fc; Efmarodocokin alfa; Drug: Vedolizumab Placebo; The matching placebo to vedolizumab (Vedolizumab Placebo) will be administered IV.; Drug: UTTR1147A Placebo; The matching placebo to UTTR1147A (UTTR1147A Placebo) will be administered IV.
Experimental: Arm 2a: UTTR1147A Dose Level 2 (Part A) + UTTR1147A (Part B); Part A: UTTR1147A dose level 2 and Vedolizumab Placebo. Part B: UTTR1147A maintenance dose and Vedolizumab Placebo.	Drug: UTTR1147A; UTTR1147A will be administered intravenously (IV) at dose levels 1, 2, or 3 in Part A, and at the maintenance dose level in Part B, per the respective arm descriptions.; Other Names: RG7880; RO7021610; IL-22Fc; Efmarodocokin alfa; Drug: Vedolizumab Placebo; The matching placebo to vedolizumab (Vedolizumab Placebo) will be administered IV.
Experimental: Arm 2b: UTTR1147A Dose Level 2 (Part A) + Placebo (Part B); Part A: UTTR1147A dose level 2 and Vedolizumab Placebo. Part B: UTTR1147A Placebo and Vedolizumab Placebo.	Drug: UTTR1147A; UTTR1147A will be administered intravenously (IV) at dose levels 1, 2, or 3 in Part A, and at the maintenance dose level in Part B, per the respective arm descriptions.; Other Names: RG7880; RO7021610; IL-22Fc; Efmarodocokin alfa; Drug: Vedolizumab Placebo; The matching placebo to vedolizumab (Vedolizumab Placebo) will be administered IV.; Drug: UTTR1147A Placebo; The matching placebo to UTTR1147A (UTTR1147A Placebo) will be administered IV.
Experimental: Arm 3a: UTTR1147A Dose Level 3 (Part A) + UTTR1147A (Part B); Part A: UTTR1147A dose level 3 and Vedolizumab Placebo. Part B: UTTR1147A maintenance dose and Vedolizumab Placebo.	Drug: UTTR1147A; UTTR1147A will be administered intravenously (IV) at dose levels 1, 2, or 3 in Part A, and at the maintenance dose level in Part B, per the respective arm descriptions.; Other Names: RG7880; RO7021610; IL-22Fc; Efmarodocokin alfa; Drug: Vedolizumab Placebo; The matching placebo to vedolizumab (Vedolizumab Placebo) will be administered IV.
Experimental: Arm 3b: UTTR1147A Dose Level 3 (Part A) + Placebo (Part B); Part A: UTTR1147A dose level 3 and Vedolizumab Placebo. Part B: UTTR1147A Placebo and Vedolizumab Placebo.	Drug: UTTR1147A; UTTR1147A will be administered intravenously (IV) at dose levels 1, 2, or 3 in Part A, and at the maintenance dose level in Part B, per the respective arm descriptions.; Other Names: RG7880; RO7021610; IL-22Fc; Efmarodocokin alfa; Drug: Vedolizumab Placebo; The matching placebo to vedolizumab (Vedolizumab Placebo) will be administered IV.; Drug: UTTR1147A Placebo; The matching placebo to UTTR1147A (UTTR1147A Placebo) will be administered IV.
Active Comparator: Arm 4: Vedolizumab; Parts A and B: Vedolizumab and UTTR1147A Placebo.	Drug: UTTR1147A Placebo; The matching placebo to UTTR1147A (UTTR1147A Placebo) will be administered IV.; Drug: Vedolizumab; Vedolizumab will be administered IV, as specified in the prescribing information.; Other Names: Entyvio
Placebo Comparator: Arm 5: Placebo; Parts A and B: UTTR1147A Placebo and Vedolizumab Placebo.	Drug: Vedolizumab Placebo; The matching placebo to vedolizumab (Vedolizumab Placebo) will be administered IV.; Drug: UTTR1147A Placebo; The matching placebo to UTTR1147A (UTTR1147A Placebo) will be administered IV.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Clinical Remission at Week 8	Clinical remission is defined as modified Mayo Clinic Score (mMCS) <= 2 with Mayo rectal bleeding subscore = 0, Mayo stool frequency subscore <=1 and Centrally read endoscopic score <= 1. Patients were classified as Non-Remitters if Week 8 assessments were missing or patient received permitted/ prohibited Rescue Therapy prior to assessment.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Sustained Remission	Sustained remission is defined as clinical remission at both Week 8 and Week 30, where clinical remission is defined as modified Mayo Clinic Score (mMCS) <= 2 with Mayo rectal bleeding subscore = 0, Mayo stool frequency subscore <=1 and Centrally read endoscopic score <= 1. Patients were classified as Non-Remitters at Week 8 or at Week 30 if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment	At Weeks 8 and 30
Maximum Serum Concentration (Cmax) of UTTR1147A		Days 1 - 29, Visit: Day 57
Minimum Serum Concentration (Cmin) of UTTR1147A		Days 1 - 29, Visit: Day 57
Percentage of Participants With Clinical Response at Week 8	Clinical response is defined as achieving clinical remission or as meeting both of the following criteria: A >= 3-point decrease from baseline in modified Mayo Clinic Score (mMCS); A >= 1-point decrease from baseline in rectal bleeding subscore or a rectal bleeding subscore of 0 or 1. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment. NOTE: An Outcome Measure Description has not been entered.	At Week 8
Percentage of Participants With Clinical Response at Week 30	Clinical response is defined as achieving clinical remission or as meeting both of the following criteria: A >= 3-point decrease from baseline in modified Mayo Clinic Score (mMCS); A >= 1-point decrease from baseline in rectal bleeding subscore or a rectal bleeding subscore of 0 or 1. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment.	At Week 30
Percentage of Participants With Endoscopic Healing at Week 8	Endoscopic healing is defined as a Mayo endoscopic subscore <= 1. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment.	At Week 8
Percentage of Participants With Endoscopic Healing at Week 30	Endoscopic healing is defined as a Mayo endoscopic subscore <= 1. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment.	At Week 30
Percentage of Participants With Endoscopic Remission at Week 8	Endoscopic remission is defined as a Mayo endoscopic subscore of 0. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment.	At Week 8
Percentage of Participants With Endoscopic Remission at Week 30	Endoscopic remission is defined as a Mayo endoscopic subscore of 0. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment.	At Week 30
Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 8, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score	The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The bowel domain score ranges from 0-27, with a higher score indicating a worse disease state.	At Week 8
Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score	The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The bowel domain score ranges from 0-27, with a higher score indicating a worse disease state.	At Week 30
Change From Baseline in UC Abdominal Signs and Symptoms at Week 8, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score	The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The functional (abdominal symptoms) domain score ranges from 0-12, with a higher score indicating a worse disease state.	At Week 8
Change From Baseline in UC Abdominal Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score	The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The functional (abdominal symptoms) domain score ranges from 0-12, with a higher score indicating a worse disease state.	At Week 30
Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 8	The IBDQ score is a Total Score summed up from across all 32 questions on the questionnaire. The Total Score range is from 32 to 224 with higher scores representing a better quality of life.	At Week 8
Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 30	The IBDQ score is a Total Score summed up from across all 32 questions on the questionnaire. The Total Score range is from 32 to 224 with higher scores representing a better quality of life.	At Week 30
Percentage of Participants With Adverse Events		Up to 30 weeks
Percentage of Participants With Presence of Anti-Drug Antibodies (ADA) at Baseline and After Drug Administration		Baseline up to 30

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2018
• Primary Completion (Actual): December 15, 2021
• Study Completion (Actual): December 15, 2021

Study Registration Dates

• First Submitted: June 1, 2018
• First Submitted That Met QC Criteria: June 13, 2018
• First Posted (Actual): June 15, 2018

Study Record Updates

• Last Update Posted (Actual): April 14, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Gastrointestinal Agents; Vedolizumab
• Other Study ID Numbers: GA39925; 2017-002350-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).

For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No