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)

Ulcerative Colitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03558152
• Other study ID #: GA39925
• Secondary ID: 2017-002350-36
• Status: Completed
• Phase: Phase 2
• Start date: October 26, 2018
• Est. completion date: December 15, 2021

Study information

• Verified date: March 2023
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 195
• Est. completion date: December 15, 2021
• Est. primary completion date: December 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

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.
• UTTR1147A Placebo
The matching placebo to UTTR1147A (UTTR1147A Placebo) will be administered IV.
• Vedolizumab
Vedolizumab will be administered IV, as specified in the prescribing information.
• Vedolizumab Placebo
The matching placebo to vedolizumab (Vedolizumab Placebo) will be administered IV.

Locations

Country	Name	City	State
Bulgaria	MHAT Saint Karidad EAD	Plovdiv
Bulgaria	Multiprofile Hospital for Active Treatment Hadji Dimitar OOD	Sliven
Georgia	LLC ARENSIA Exploratory Medicine	Tbilisi
Germany	Gastroenterologische Spezialpraxis-Berlin-Karlshorst	Berlin
Germany	Universitaetsklinikum Carl Gustav Carus TU Dresden	Dresden
Germany	Universitatsklinikum Schleswig-Holstein	Lubeck
Germany	St. Marien Krankenhaus; Med. Klinik	Ludwigshafen
Germany	Universitätsklinikum Ulm; Klinik für Innere Medizin II	Ulm
Greece	Iatriko Palaiou Falirou; Gastrointestinal Department	Palaio Faliro
Greece	EUROMEDICA General Clinic of Thessaloniki; Gastroenterology Department	Thessaloniki
Hungary	Magyar Honvédség Egészségügyi Központ; Országos Haemophilia Központ	Budapest
Ireland	Portiuncula Hospital, Ballinasloe	Co Galway
Israel	Shaare Zedek Medical Center; Bait Vagan	Jerusalem
Italy	ASST di Monza - Azienda Ospedaliera San Gerardo; U.O. Farmacia -Settore A - Corpo Posteriore	Monza	Lombardia
Italy	Azienda Ospedaliera Di Padova	Padova	Veneto
Italy	Complesso Integrato Columbus	Roma	Lazio
Italy	Policlinico Universitario Campus Biomedico Di Roma	Roma	Lazio
Italy	Istituto Clinico Humanitas	Rozzano (MI)	Lombardia
Moldova, Republic of	ICS ARENSIA Exploratory Medicine	Chisinau
Poland	SPZOZ Uniwersytecki SK nr 1 im N. Barlickiego UM w Lodzi; Oddz. Klin. Gastroenter. Og. i Onk.	?ód?
Poland	Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy; Centrum Endoskopii Zabiegowej	Bydgoszcz
Poland	Synexus Polska Sp. z o.o. Oddzial w Czestochowie	Cz?stochowa
Poland	Synexus Polska Sp. z o.o. Oddzial w Gdansku	Gda?sk
Poland	Economicus - NZOZ ALL-MEDICUS; Zaklad Gastroenterologii	Katowice
Poland	Synexus - Katowice	Katowice
Poland	ETG Kielce	Kielce
Poland	Gastromed SPK Niepubliczny Zaklad Opieki Zdrowotnej	Lublin
Poland	Klimed Marek Klimkiewicz	Piotrków Trybunalski
Poland	Clinical Research Center Sp. z o.o. MEDIC-R Spó?ka Komandytowa	Pozna?
Poland	Synexus Polska Sp. z o.o. Oddzial w Poznaniu	Pozna?
Poland	Endoskopia Sp. z o.o.	Sopot
Poland	Gastromed Kopon Zmudzinski i	Toru?
Poland	Centrum Zdrowia MDM	Warszawa
Poland	Jaroslaw Kierkus Prywatna Prakyka Lekarska	Warszawa
Poland	Melita Medical	Wroc?aw
Poland	Przychodnia EuroMediCare	Wroc?aw
Poland	Synexus Polska Sp. z o.o. Oddzial we Wroclawiu	Wroc?aw
Russian Federation	Irkutsk Research Centre Hospital of Siberian department of Russian Academy of Science	Irkutsk
Russian Federation	Rostov State Medical University; Cardiorheumatology Department	Rostov-na-Donu
Russian Federation	Medical University Reaviz	Samara
Russian Federation	Saint Martyr Elizabeth City Hospital	Sankt-peterburg	Sankt Petersburg
Russian Federation	North-West State Medical University n.a. I.I. Mechnikov	St. Petersburg
Serbia	Clinical Hospital Center Zvezdara	Belgrade
Serbia	KBC Dr Dragisa Misovic Dedinje	Belgrade
Serbia	University Hospital Medical Center Bezanijska kosa	Belgrade
Serbia	Clinical Center Kragujevac; Clinic Of Psychiatry	Kragujevac
Serbia	General Hospital Vrsac	Vrsac
Serbia	Clinical Hospital Centre Zemun	Zemun
Serbia	General Hospital Djordje Joanovic - Zrenjanin	Zrenjanin
Spain	Hospital de Gran Canaria Dr. Negrin; Servicio de Aparato Digestivo	Las Palmas de Gran Canaria	LAS Palmas
Spain	Hospital Universitario de Torrejon	Torrejon de Ardoz	Madrid
Ukraine	Regional Municipal Institution Chernivtsi Regional Clinical Hospital; Gastroenterology department	Chernivtsi	Chernihiv Governorate
Ukraine	Medical Center of LLC Medical Center Family Medicine Clinic; Endoscopy & Gastroenterology	Dnipr	Polissya Okruha
Ukraine	ME Dnipropetrovsk Regional Clinical Hospital n.a. I.I Mechnykov Dnipropetrovsk Regional Council	Dnipro	KIEV Governorate
Ukraine	Treatment and Diagnostic Center of LLC MRT Elit	Kropyvnytskyi	KIEV Governorate
Ukraine	Med Center of International Institute of Clinical Trials LLC; Medical Center "OK!Clinic+"	Kyiv	KIEV Governorate
Ukraine	Medical Center of Edelweiss Medics LLC	Kyiv	KIEV Governorate
Ukraine	Medical Center of Limited Liability Company ?Harmoniya krasy?	Kyiv	KIEV Governorate
Ukraine	Medical Center of LLC Medical Center Dopomoga Plus	Kyiv	KIEV Governorate
Ukraine	Medical Center of LLC Medical Clinic Blagomed	Kyiv	KIEV Governorate
Ukraine	Synexus Affiliate - MC of LLC Medbud-Clinic	Kyiv	KIEV Governorate
Ukraine	Ternopil University Hospital; Regional Center of Gastroenterology with Hepatology	Ternopil	Katerynoslav Governorate
Ukraine	Transcarpathian Regional Clinical Hospital n.a. A. Novak; Rheumatology Department	Uzhgorod
Ukraine	City Clinical Hospital #1; Department of Gastroenterology	Vinnytsia	Kharkiv Governorate
Ukraine	Clinic of SRI of Invalid Rehab. (ESTC) of VNMU n.a. M.I.Pyrohov	Vinnytsia	Podolia Governorate
Ukraine	Medical Center of Diaservice LLC; Division of clinical trials conduct, Department #3	Zaporizhzhia
Ukraine	Medical Center of LLC Diaservis	Zaporizhzhia	KIEV Governorate
Ukraine	Municipal Institution Zaporizhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council	Zaporizhzhia	Kharkiv Governorate
Ukraine	Medical Centre of PE First Private Clinic	Zhytomir	Crimean Regional Governmenta
United Kingdom	Kings College Hospital	London
United States	Carolina Digestive Diseases	Greenville	North Carolina
United States	University of Utah School of Medicine; Gastroenterology Division	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Bulgaria,  Georgia,  Germany,  Greece,  Hungary,  Ireland,  Israel,  Italy,  Moldova, Republic of,  Poland,  Russian Federation,  Serbia,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Maximum Serum Concentration (Cmax) of UTTR1147A		Days 1 - 29, Visit: Day 57
Secondary	Minimum Serum Concentration (Cmin) of UTTR1147A		Days 1 - 29, Visit: Day 57
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percentage of Participants With Adverse Events		Up to 30 weeks
Secondary	Percentage of Participants With Presence of Anti-Drug Antibodies (ADA) at Baseline and After Drug Administration		Baseline up to 30