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)
- Conditions
- Ulcerative Colitis
- Interventions
- Registration Number
- NCT03558152
- Lead Sponsor
- Genentech, Inc.
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 195
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 3a: UTTR1147A Dose Level 3 (Part A) + UTTR1147A (Part B) Vedolizumab Placebo Part A: UTTR1147A dose level 3 and Vedolizumab Placebo. Part B: UTTR1147A maintenance dose and Vedolizumab Placebo. Arm 3b: UTTR1147A Dose Level 3 (Part A) + Placebo (Part B) Vedolizumab Placebo Part A: UTTR1147A dose level 3 and Vedolizumab Placebo. Part B: UTTR1147A Placebo and Vedolizumab Placebo. Arm 1a: UTTR1147A Dose Level 1 (Part A) + UTTR1147A (Part B) UTTR1147A Part A: UTTR1147A dose level 1 and Vedolizumab Placebo. Part B: UTTR1147A maintenance dose and Vedolizumab Placebo. Arm 1a: UTTR1147A Dose Level 1 (Part A) + UTTR1147A (Part B) Vedolizumab Placebo Part A: UTTR1147A dose level 1 and Vedolizumab Placebo. Part B: UTTR1147A maintenance dose and Vedolizumab Placebo. Arm 1b: UTTR1147A Dose Level 1 (Part A) + Placebo (Part B) UTTR1147A Part A: UTTR1147A dose level 1 and Vedolizumab Placebo. Part B: UTTR1147A Placebo and Vedolizumab Placebo. Arm 1b: UTTR1147A Dose Level 1 (Part A) + Placebo (Part B) UTTR1147A Placebo Part A: UTTR1147A dose level 1 and Vedolizumab Placebo. Part B: UTTR1147A Placebo and Vedolizumab Placebo. Arm 1b: UTTR1147A Dose Level 1 (Part A) + Placebo (Part B) Vedolizumab Placebo Part A: UTTR1147A dose level 1 and Vedolizumab Placebo. Part B: UTTR1147A Placebo and Vedolizumab Placebo. Arm 2a: UTTR1147A Dose Level 2 (Part A) + UTTR1147A (Part B) UTTR1147A Part A: UTTR1147A dose level 2 and Vedolizumab Placebo. Part B: UTTR1147A maintenance dose and Vedolizumab Placebo. Arm 2a: UTTR1147A Dose Level 2 (Part A) + UTTR1147A (Part B) Vedolizumab Placebo Part A: UTTR1147A dose level 2 and Vedolizumab Placebo. Part B: UTTR1147A maintenance dose and Vedolizumab Placebo. Arm 2b: UTTR1147A Dose Level 2 (Part A) + Placebo (Part B) UTTR1147A Part A: UTTR1147A dose level 2 and Vedolizumab Placebo. Part B: UTTR1147A Placebo and Vedolizumab Placebo. Arm 2b: UTTR1147A Dose Level 2 (Part A) + Placebo (Part B) UTTR1147A Placebo Part A: UTTR1147A dose level 2 and Vedolizumab Placebo. Part B: UTTR1147A Placebo and Vedolizumab Placebo. Arm 2b: UTTR1147A Dose Level 2 (Part A) + Placebo (Part B) Vedolizumab Placebo Part A: UTTR1147A dose level 2 and Vedolizumab Placebo. Part B: UTTR1147A Placebo and Vedolizumab Placebo. Arm 3a: UTTR1147A Dose Level 3 (Part A) + UTTR1147A (Part B) UTTR1147A Part A: UTTR1147A dose level 3 and Vedolizumab Placebo. Part B: UTTR1147A maintenance dose and Vedolizumab Placebo. Arm 3b: UTTR1147A Dose Level 3 (Part A) + Placebo (Part B) UTTR1147A Part A: UTTR1147A dose level 3 and Vedolizumab Placebo. Part B: UTTR1147A Placebo and Vedolizumab Placebo. Arm 3b: UTTR1147A Dose Level 3 (Part A) + Placebo (Part B) UTTR1147A Placebo Part A: UTTR1147A dose level 3 and Vedolizumab Placebo. Part B: UTTR1147A Placebo and Vedolizumab Placebo. Arm 4: Vedolizumab UTTR1147A Placebo Parts A and B: Vedolizumab and UTTR1147A Placebo. Arm 5: Placebo UTTR1147A Placebo Parts A and B: UTTR1147A Placebo and Vedolizumab Placebo. Arm 5: Placebo Vedolizumab Placebo Parts A and B: UTTR1147A Placebo and Vedolizumab Placebo. Arm 4: Vedolizumab Vedolizumab Parts A and B: Vedolizumab and UTTR1147A Placebo.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Clinical Remission at Week 8 8 weeks 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Sustained Remission At Weeks 8 and 30 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 assessmentMaximum Serum Concentration (Cmax) of UTTR1147A Days 1 - 29, Visit: Day 57 Percentage of Participants With Endoscopic Remission at Week 30 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.
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 At Week 8 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.
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 At Week 8 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.
Percentage of Participants With Clinical Response at Week 8 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.Percentage of Participants With Clinical Response at Week 30 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.Minimum Serum Concentration (Cmin) of UTTR1147A Days 1 - 29, Visit: Day 57 Percentage of Participants With Endoscopic Healing at Week 30 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.
Percentage of Participants With Endoscopic Healing at Week 8 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.
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 At Week 30 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.
Percentage of Participants With Endoscopic Remission at Week 8 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.
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 At Week 30 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.
Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 8 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.
Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 30 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.
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
Trial Locations
- Locations (72)
Synexus Polska Sp. z o.o. Oddzial w Gdansku
🇵🇱Gda?sk, Poland
Clinical Hospital Center Zvezdara
🇷🇸Belgrade, Serbia
Klimed Marek Klimkiewicz
🇵🇱Piotrków Trybunalski, Poland
Gastromed Kopon Zmudzinski i
🇵🇱Toru?, Poland
Complesso Integrato Columbus
🇮🇹Roma, Lazio, Italy
Synexus Polska Sp. z o.o. Oddzial w Czestochowie
🇵🇱Cz?stochowa, Poland
Synexus Polska Sp. z o.o. Oddzial we Wroclawiu
🇵🇱Wroc?aw, Poland
Melita Medical
🇵🇱Wroc?aw, Poland
Portiuncula Hospital, Ballinasloe
🇮🇪Co Galway, Ireland
Policlinico Universitario Campus Biomedico Di Roma
🇮🇹Roma, Lazio, Italy
Synexus - Katowice
🇵🇱Katowice, Poland
Synexus Polska Sp. z o.o. Oddzial w Poznaniu
🇵🇱Pozna?, Poland
Clinical Hospital Centre Zemun
🇷🇸Zemun, Serbia
Clinical Center Kragujevac; Clinic Of Psychiatry
🇷🇸Kragujevac, Serbia
General Hospital Vrsac
🇷🇸Vrsac, Serbia
Medical University Reaviz
🇷🇺Samara, Russian Federation
Universitätsklinikum Ulm; Klinik für Innere Medizin II
🇩🇪Ulm, Germany
Carolina Digestive Diseases
🇺🇸Greenville, North Carolina, United States
University of Utah School of Medicine; Gastroenterology Division
🇺🇸Salt Lake City, Utah, United States
MHAT Saint Karidad EAD
🇧🇬Plovdiv, Bulgaria
LLC ARENSIA Exploratory Medicine
🇬🇪Tbilisi, Georgia
Multiprofile Hospital for Active Treatment Hadji Dimitar OOD
🇧🇬Sliven, Bulgaria
Gastroenterologische Spezialpraxis-Berlin-Karlshorst
🇩🇪Berlin, Germany
Universitaetsklinikum Carl Gustav Carus TU Dresden
🇩🇪Dresden, Germany
St. Marien Krankenhaus; Med. Klinik
🇩🇪Ludwigshafen, Germany
Universitatsklinikum Schleswig-Holstein
🇩🇪Lubeck, Germany
Iatriko Palaiou Falirou; Gastrointestinal Department
🇬🇷Palaio Faliro, Greece
Shaare Zedek Medical Center; Bait Vagan
🇮🇱Jerusalem, Israel
Magyar Honvédség Egészségügyi Központ; Országos Haemophilia Központ
ðŸ‡ðŸ‡ºBudapest, Hungary
EUROMEDICA General Clinic of Thessaloniki; Gastroenterology Department
🇬🇷Thessaloniki, Greece
ASST di Monza - Azienda Ospedaliera San Gerardo; U.O. Farmacia -Settore A - Corpo Posteriore
🇮🇹Monza, Lombardia, Italy
Istituto Clinico Humanitas
🇮🇹Rozzano (MI), Lombardia, Italy
Azienda Ospedaliera Di Padova
🇮🇹Padova, Veneto, Italy
ICS ARENSIA Exploratory Medicine
🇲🇩Chisinau, Moldova, Republic of
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
ETG Kielce
🇵🇱Kielce, Poland
Economicus - NZOZ ALL-MEDICUS; Zaklad Gastroenterologii
🇵🇱Katowice, Poland
Gastromed SPK Niepubliczny Zaklad Opieki Zdrowotnej
🇵🇱Lublin, Poland
Clinical Research Center Sp. z o.o. MEDIC-R Spó?ka Komandytowa
🇵🇱Pozna?, Poland
Endoskopia Sp. z o.o.
🇵🇱Sopot, Poland
Centrum Zdrowia MDM
🇵🇱Warszawa, Poland
Jaroslaw Kierkus Prywatna Prakyka Lekarska
🇵🇱Warszawa, Poland
Przychodnia EuroMediCare
🇵🇱Wroc?aw, Poland
Irkutsk Research Centre Hospital of Siberian department of Russian Academy of Science
🇷🇺Irkutsk, Russian Federation
Saint Martyr Elizabeth City Hospital
🇷🇺Sankt-peterburg, Sankt Petersburg, Russian Federation
Rostov State Medical University; Cardiorheumatology Department
🇷🇺Rostov-na-Donu, Russian Federation
North-West State Medical University n.a. I.I. Mechnikov
🇷🇺St. Petersburg, Russian Federation
KBC Dr Dragisa Misovic Dedinje
🇷🇸Belgrade, Serbia
University Hospital Medical Center Bezanijska kosa
🇷🇸Belgrade, Serbia
General Hospital Djordje Joanovic - Zrenjanin
🇷🇸Zrenjanin, Serbia
Hospital de Gran Canaria Dr. Negrin; Servicio de Aparato Digestivo
🇪🇸Las Palmas de Gran Canaria, LAS Palmas, Spain
Ternopil University Hospital; Regional Center of Gastroenterology with Hepatology
🇺🇦Ternopil, Katerynoslav Governorate, Ukraine
Hospital Universitario de Torrejon
🇪🇸Torrejon de Ardoz, Madrid, Spain
Regional Municipal Institution Chernivtsi Regional Clinical Hospital; Gastroenterology department
🇺🇦Chernivtsi, Chernihiv Governorate, Ukraine
Medical Centre of PE First Private Clinic
🇺🇦Zhytomir, Crimean Regional Governmenta, Ukraine
City Clinical Hospital #1; Department of Gastroenterology
🇺🇦Vinnytsia, Kharkiv Governorate, Ukraine
ME Dnipropetrovsk Regional Clinical Hospital n.a. I.I Mechnykov Dnipropetrovsk Regional Council
🇺🇦Dnipro, KIEV Governorate, Ukraine
Medical Center of LLC Medical Center Dopomoga Plus
🇺🇦Kyiv, KIEV Governorate, Ukraine
Synexus Affiliate - MC of LLC Medbud-Clinic
🇺🇦Kyiv, KIEV Governorate, Ukraine
Medical Center of LLC Diaservis
🇺🇦Zaporizhzhia, KIEV Governorate, Ukraine
Clinic of SRI of Invalid Rehab. (ESTC) of VNMU n.a. M.I.Pyrohov
🇺🇦Vinnytsia, Podolia Governorate, Ukraine
Medical Center of LLC Medical Center Family Medicine Clinic; Endoscopy & Gastroenterology
🇺🇦Dnipr, Polissya Okruha, Ukraine
Transcarpathian Regional Clinical Hospital n.a. A. Novak; Rheumatology Department
🇺🇦Uzhgorod, Ukraine
Kings College Hospital
🇬🇧London, United Kingdom
Medical Center of Diaservice LLC; Division of clinical trials conduct, Department #3
🇺🇦Zaporizhzhia, Ukraine
Medical Center of LLC Medical Clinic Blagomed
🇺🇦Kyiv, KIEV Governorate, Ukraine
Med Center of International Institute of Clinical Trials LLC; Medical Center "OK!Clinic+"
🇺🇦Kyiv, KIEV Governorate, Ukraine
Municipal Institution Zaporizhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council
🇺🇦Zaporizhzhia, Kharkiv Governorate, Ukraine
Treatment and Diagnostic Center of LLC MRT Elit
🇺🇦Kropyvnytskyi, KIEV Governorate, Ukraine
Medical Center of Limited Liability Company ?Harmoniya krasy?
🇺🇦Kyiv, KIEV Governorate, Ukraine
Medical Center of Edelweiss Medics LLC
🇺🇦Kyiv, KIEV Governorate, Ukraine