A Study With GB004 in Adult Subjects With Active Ulcerative Colitis (UC)

A Phase 2, Randomized, Double-blind, Placebo-controlled, Multi-center Study to Evaluate GB004 in Adult Subjects With Mild-to-moderate Active Ulcerative Colitis

A 2-part study, comprising of a 36-week placebo-controlled period (PCP) and a 24-week open-label extension (OLE) period, to assess the efficacy and safety of 2 dose regimens of GB004 when added to background UC therapy of 5-aminosalicylate (5-ASA) with or without systemic steroids.

Study Overview

• Status: Terminated
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Placebo; Drug: GB004

• Study Type: Interventional
• Enrollment (Actual): 236
• Phase: Phase 2

Contacts and Locations

Study Locations

• Georgia
  • Tbilisi, Georgia, 0160
    • Ltd Aversi Clinic
  • Tbilisi, Georgia, 0160
    • JSC Infectious Diseases, AIDS and Clinical Immunology Research Center
  • Tbilisi, Georgia, 0160
    • LTD Central University Clinic After Academic N. Kipshidze
  • Tbilisi, Georgia, 0160
    • LTD Coloproctological Center of Georgia
  • Tbilisi, Georgia, 0172
    • Malkhaz Katsiashvili Multiprofile Emergency Medicine Center LTD
• Korea, Republic of
  • Busan, Korea, Republic of, 49201
    • Dong-A University Hospital
  • Busan, Korea, Republic of, 48018
    • Inje University Heaundae Paik Hospital
  • Daegu, Korea, Republic of, 41404
    • Kyungpook National University Chilgok Hospital
• Moldova, Republic of
  • Chisinau, Moldova, Republic of, MD2025
    • PMSI Republican Clinical Hospital "Timofei Mosneaga"
• Poland
  • Bydgoszcz, Poland, 85-794
    • CLINSANTE Clinical Research Center Civil Law Partnership Ewa Galczak-Nowak, Malgorzata Trzaska
  • Elblag, Poland, 82-300
    • St. John Paul 2 Municipal Hospital in Elblag, Department of Internal Medicine
  • Jelenia Gora, Poland, 58-500
    • Clinical Research Center of Karkonosze - Lexmedica Limited Liability Company, KCBK - LEXMEDICA
  • Katowice, Poland, 40-752
    • Professor K. Gibinski University Clinical Centre of the Medical University of Silesia in Katowice
  • Krakow, Poland, 31-156
    • "LANDA" Katarzyna Agata Landa, Landa" Specialist Doctor's Offices
  • Oswiecim, Poland, 32-600
    • Medicome Limited Liability Company, Oswiecim Clinical Trial Centre
  • Sopot, Poland, 81-756
    • Marek Horynski, MD, Ph.D. Individual Specialist Medical Practice [Specjialistyczna Praktyka Lekarska Dr med. Marek Horynski]
  • Staszow, Poland, 28-200
    • "NOWE ZDROWIE-CK" Kieltucki and Partners General Partnership, NOWE ZDROWIE-CK
  • Toruń, Poland, 87-100
    • "Gastromed" Torun Gastrology Centre [Torunskie Centrum Gastrologiczne "Gastromed"]
  • Warsaw, Poland, 00-635
    • EB GROUP Limited Liability Company, MDM Health Centre
  • Warsaw, Poland, 00-728
    • WIP Warsaw IBD Point Profesor Kierkuś
  • Warsaw, Poland, 02-665
    • Reuma Park Clinic Limited Liability Company Limited Partnership, Reuma Park Medical Center
  • Warsaw, Poland, 03-580
    • VIVAMED Non-Public Healthcare Facility
  • Wroclaw, Poland, 51-162
    • Clinical Research Center Piotr Napora Medical Doctors Professional Partnership
• Romania
  • Bucharest, Romania, 020125
    • Colentina Clinical Hospital
• Russian Federation
  • Barnaul, Russian Federation, 656015
    • Limited Liability Company Joint Venture Diagnostic Center "Biotherm"
  • Bataysk, Russian Federation, 346880
    • "Myod" Ltd.
  • Krasnoyarsk, Russian Federation, 660037
    • Federal Siberian Research Clinical Center under the Federal Medical Biological Agency
  • Moscow, Russian Federation, 115516
    • Moscow State-Funded Healthcare Institution City Clinical Hospital n.a. V.M. Buyanov under Moscow Healthcare Department
  • Novosibirsk, Russian Federation, 630007
    • Novosibirskiy Gastrocenter, LLC
  • Novosibirsk, Russian Federation, 630005
    • Medical Center SibNovoMed, Limited Liability Company
  • Novosibirsk, Russian Federation, 630089
    • Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
  • Orenburg, Russian Federation, 460051
    • Medical Diagnostic Center, Limited Liability Company
  • Penza, Russian Federation, 440026
    • Penza Regional Clinical Hospital named after N.N. Burdenko
  • Pyatigorsk, Russian Federation, 357502
    • Clinic UZI 4D, Limited Liability Company
  • St Petersburg, Russian Federation, 191015
    • S.M. Kirov Miltiary Medical Academy
  • St. Petersburg, Russian Federation, 191015
    • St. Petersburg State-Funded Healthcare Institution: City Outpatient Care Unit No. 38
  • St. Petersburg, Russian Federation, 197110
    • Consultation and Diagnostics Center and Outpatient Care Unit under the Department of Presidential Affairs
  • Veliky Novgorod, Russian Federation, 173008
    • Regional State-Funded Healthcare Institution: Novgorod Regional Clinic Hospital
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center Zemun
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center "Dr Dragisa Misovic Dedinje'' local lab
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center "Dr Dragisa Misovic Dedinje''
  • Belgrade, Serbia, 11000
    • Zvezdara University Medical Center-local lab
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac
  • Zrenjanin, Serbia, 23000
    • General Hospital "Djordje Joanovic"
• Ukraine
  • Cherkasy, Ukraine, 18009
    • Communal Nonprofit Enterprise "Cherkasy Regional Hospital of Cherkasy Oblast Council"
  • Chernivtsi, Ukraine, 58001
    • Regional Communal Noncommercial Enterprise "Chernivtsi Regional Clinical Hospital" Site 9519
  • Chernivtsi, Ukraine, 58001
    • Regional Communal Noncommercial Enterprise "Chernivtsi Regional Clinical Hospital" Site 9527
  • Ivano-Frankivsk, Ukraine, 76008
    • Public Non-Profit Enterprise "Regional Clinical Hospital under Ivano-Frankivsk Regional Council"
  • Kharkiv, Ukraine, 61037
    • PNPE "Prof. O.O. Shalimov City Clinical Hospital #2" under Kharkiv City Council
  • Kharkiv, Ukraine, 61058
    • Public Non-Profit Enterprise under Kharkiv Regional Council "Regional Clinical Hospital"
  • Kyiv, Ukraine, 01030
    • PNPE "Kyiv City Clinical Hospital #18" under the Executive Body of Kyiv City Council
  • Kyiv, Ukraine, 01135
    • Medical Center of the Limited Liability Company "Harmoniia Krasy"
  • Kyiv, Ukraine, 02091
    • Medical Center "OK!Clinic+" of the Company with Limited Liability "International Institute of Clinical Research"
  • Kyiv, Ukraine, 04050
    • Medical center of the limited liability company "Medical center "Consilium Medical"
  • Kyiv, Ukraine, 04078
    • Public Non-Profit Enterprise under Kyiv Regional Council "Kyiv Regional Hospital"
  • Lutsk, Ukraine, 43005
    • The Municipal Enterprise "Volyn Regional Clinical Hospital" of the Volyn Regional Council
  • Lviv, Ukraine, 79010
    • Communal Noncommercial Enterprise of Lviv Regional Council "Lviv Regional Clinical Hospital"
  • Odesa, Ukraine, 65025
    • Public Non-Profit Enterprise "Odesa Regional Clinical Hospital" under Odesa Regional Council
  • Poltava, Ukraine, 36011
    • Public Enterprise "Poltava M.V. Sklifosovsky Regional Clinical Hospital under Poltava Regional Council"
  • Vinnytsia, Ukraine, 21028
    • MNPE "Vinnytsia Regional Clinical Hospital named after M.I. Pirogov Vinnytsia Regional Council"
  • Vinnytsia, Ukraine, 21029
    • Communal Non-Commercial Enterprise "Vinnytsia City Clinical Hospital #1
  • Zaporizhia, Ukraine, 69005
    • PNPE "City Hospital of Urgent and Emergency Medical Care under Zaporizhia City Council"
  • Zaporizhia, Ukraine, 69600
    • MNPE "Zaporizhia Regional Clinical Hospital" of Zaporizhia Regional Council
  • Zhytomyr, Ukraine, 10002
    • Limited Liability Company "Medibor"
• United States
  • California
    • Encinitas, California, United States, 92024
      • B G Clinical Research, Inc.
    • Lancaster, California, United States, 93534
      • Gastro Care Institute
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Texas Digestive Disease Consultants
    • Lafayette, Louisiana, United States, 70503
      • Gastroenterology Clinic of Acadiana
    • Monroe, Louisiana, United States, 71201
      • Delta Research Partners
  • Michigan
    • Ypsilanti, Michigan, United States, 48197
      • Huron Gastroenterology Associates
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Las Vegas Medical Research
  • New Jersey
    • Freehold, New Jersey, United States, 07728
      • Freehold Endoscopy Associates, LLC d/b/a/ Endoscopy Center of Monmouth County
  • Ohio
    • Mentor, Ohio, United States, 44060
      • Great Lakes Gastroenterology Research, LLC
  • Texas
    • Southlake, Texas, United States, 76092
      • Texas Digestive Disease Consultant
  • Washington
    • Bellevue, Washington, United States, 98004
      • Washington Gastroenterology, PLLC
    • Tacoma, Washington, United States, 98405
      • Washington Gastroenterology, PLCC

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult male and female subjects aged ≥ 18 years at the time of signing the informed consent form (ICF) prior to initiation of any study specific activities/procedures.
• UC diagnosed at least 3 months prior to first dose of investigational product (IP) on Day 1.

• Currently receiving treatment for UC, on a stable dose for at least 2 weeks prior to flexible sigmoidoscopy or colonoscopy, with oral 5-ASA (eg, mesalamine, sulfasalazine) alone or with one of the following oral treatments:

  1. prednisone ≤ 20 mg/day or equivalent or
  2. beclomethasone ≤ 5 mg/day or
  3. budesonide or budesonide multi-matrix (MMX) of ≤ 9 mg/day

Exclusion Criteria:

• Prior approved biologic therapy used for the treatment of UC.
• Diagnosis of Crohn's disease, indeterminate colitis, or pouchitis, or presence of bacterial or parasitic infection.
• Tofacitinib, oral cyclosporine, sirolimus or mycophenolate mofetil within 8 weeks of Day 1.
• Azathioprine, or 6-mercaptopurine within 1 day of Day 1.

NOTE: Other Inclusion/Exclusion criteria may apply per protocol.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: PCP Placebo; PCP Placebo for oral administration for 36 weeks	Drug: Placebo; oral tablet
Experimental: PCP GB004 480 mg QD; PCP GB004 480 mg QD for oral administration for 36 weeks	Drug: GB004; oral tablet
Experimental: PCP GB004 480 mg BID; PCP GB004 480 mg BID for oral administration for 36 weeks	Drug: GB004; oral tablet
Experimental: Open-Label Extension (OLE) GB004 480 mg BID; OLE GB004 480 mg BID for oral administration for 24 weeks	Drug: GB004; oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Clinical Remission at PCP Week 12	Clinical remission is defined as a Modified Mayo score ≤ 2, with a rectal bleeding subscore of 0, stool frequency subscore of 0 or 1 (with a ≥ 1 point decrease from baseline), and endoscopic subscore of 0 or 1. The Modified Mayo score is an endpoint measure composed of: Stool frequency, Rectal bleeding, and Endoscopic subscores (where the Endoscopic subscore value of 1 does not include friability), each ranging from 0 to 3, that are summed to give a total score ranging from 0 to 9 points, with higher scores indicating greater severity.	At PCP Week 12
Percentage of Participants With a Treatment Emergent Adverse Event	An adverse event (AE) is any untoward medical occurrence in a participant, whether or not considered related to study treatment. Abnormal laboratory test results or other safety assessments, including those that worsened from baseline, that were considered clinically significant in the medical and scientific judgment of the investigator were to be reported as AEs. An AE was considered treatment-emergent to the OLE if it started on or after the first dose of OLE study treatment.	From first dose of OLE study treatment through OLE Week 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Clinical Response at PCP Week 12	Clinical response is defined as a reduction in Modified Mayo score of ≥ 2 points and ≥ 35% from baseline, including a decrease in rectal bleeding subscore of ≥ 1 or absolute rectal bleeding subscore of ≤ 1. The Modified Mayo score is an endpoint measure composed of: Stool frequency, Rectal bleeding, and Endoscopic subscores (where the Endoscopic subscore value of 1 does not include friability), each ranging from 0 to 3, that are summed to give a total score ranging from 0 to 9 points, with higher scores indicating greater severity.	At PCP Week 12
Percentage of Participants With Histologic Remission at PCP Week 12	Histologic remission is defined as Robarts Histopathology Index (RHI) ≤ 3 with lamina propria neutrophils RHI subscore = 0 and neutrophils in epithelium RHI subscore = 0. Histologic remission is evaluated among subjects with both baseline lamina propria neutrophils and neutrophils in epithelium RHI subscores > 0. The RHI is a validated instrument that measures histologic disease activity and consists of 4 subscores (chronic inflammatory infiltrate, lamina propria neutrophils, neutrophils in epithelium, and erosion or ulceration). Each subscore ranges from 0-3, with higher subscores indicating greater histologic disease activity. The RHI score is calculated as: (1 x chronic inflammatory infiltrate) + (2 x lamina propria neutrophils) + (3 x neutrophils in epithelium) + (5 x erosion or ulceration). The RHI therefore ranges from 0-33, with higher scores indicating greater histologic disease activity.	At PCP Week 12
Percentage of Participants With Endoscopic Improvement at PCP Week 12	Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. The endoscopic subscore is a component of the Modified Mayo score and is assessed on a 0-3 scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions); and 3 = Severe disease (spontaneous bleeding, ulceration). Higher scores indicate greater endoscopic disease severity. An endoscopic subscore of 1 does not include friability; an endoscopy with friability is assessed an endoscopic subscore of at least 2.	At PCP Week 12
Percentage of Participants With Mucosal Healing at PCP Week 12	Mucosal healing is defined as endoscopic improvement and histologic remission. Please see Secondary Outcome Measure Descriptions above for Percentage of Participants With Endoscopic Improvement at PCP Week 12 and for Percentage of Participants With Histologic Remission at PCP Week 12 for information on the measures of endoscopic improvement and histologic remission, respectively.	At PCP Week 12
Percentage of Participants With Clinical Remission at PCP Week 36	Clinical remission is defined as a Modified Mayo score ≤ 2, with a rectal bleeding subscore of 0, stool frequency subscore of 0 or 1 (with a ≥ 1 point decrease from baseline), and endoscopic subscore of 0 or 1. The Modified Mayo score is an endpoint measure composed of: Stool frequency, Rectal bleeding, and Endoscopic subscores (where the Endoscopic subscore value of 1 does not include friability), each ranging from 0 to 3, that are summed to give a total score ranging from 0 to 9 points, with higher scores indicating greater severity.	At PCP Week 36
Percentage of Participants With Clinical Response at PCP Week 36	Clinical response is defined as a reduction in Modified Mayo score of ≥ 2 points and ≥ 35% from baseline, including a decrease in rectal bleeding subscore of ≥ 1 or absolute rectal bleeding subscore of ≤ 1. The Modified Mayo score is an endpoint measure composed of: Stool frequency, Rectal bleeding, and Endoscopic subscores (where the Endoscopic subscore value of 1 does not include friability), each ranging from 0 to 3, that are summed to give a total score ranging from 0 to 9 points, with higher scores indicating greater severity.	At PCP Week 36
Percentage of Participants With Histologic Remission at PCP Week 36	Histologic remission is defined as Robarts Histopathology Index (RHI) ≤ 3 with lamina propria neutrophils RHI subscore = 0 and neutrophils in epithelium RHI subscore = 0. The RHI is a validated instrument that measures histologic disease activity and consists of 4 subscores (chronic inflammatory infiltrate, lamina propria neutrophils, neutrophils in epithelium, and erosion or ulceration). Each subscore ranges from 0-3, with higher subscores indicating greater histologic disease activity. The RHI score is calculated as: (1 x chronic inflammatory infiltrate) + (2 x lamina propria neutrophils) + (3 x neutrophils in epithelium) + (5 x erosion or ulceration). The RHI therefore ranges from 0-33, with higher scores indicating greater histologic disease activity.	At PCP Week 36
Percentage of Participants With Endoscopic Improvement at PCP Week 36	Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. The endoscopic subscore is a component of the Modified Mayo score and is assessed on a 0-3 scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions); and 3 = Severe disease (spontaneous bleeding, ulceration). Higher scores indicate greater endoscopic disease severity. An endoscopic subscore of 1 does not include friability; an endoscopy with friability is assessed an endoscopic subscore of at least 2.	At PCP Week 36
Percentage of Participants With Mucosal Healing at PCP Week 36	Mucosal healing is defined as endoscopic improvement and histologic remission. Please see Secondary Outcome Measure Descriptions above for Percentage of Participants With Endoscopic Improvement at PCP Week 36 and for Percentage of Participants With Histologic Remission at PCP Week 36 for information on the measures of endoscopic improvement and histologic remission, respectively.	At PCP Week 36

Collaborators and Investigators

• Sponsor: GB004, Inc.
• Investigators: Study Director: Barrett Levesque, MD, Gossamer Bio Inc.

Publications and helpful links

General Publications

• Danese S, Levesque BG, Feagan BG, Jucov A, Bhandari BR, Pai RK, Taylor Meadows K, Kirby BJ, Bruey JM, Olson A, Osterhout R, Van Biene C, Ford J, Aranda R, Raghupathi K, Sandborn WJ. Randomised clinical trial: a phase 1b study of GB004, an oral HIF-1alpha stabiliser, for treatment of ulcerative colitis. Aliment Pharmacol Ther. 2022 Feb;55(4):401-411. doi: 10.1111/apt.16753. Epub 2022 Jan 10.

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2020
• Primary Completion (Actual): June 1, 2022
• Study Completion (Actual): June 1, 2022

Study Registration Dates

• First Submitted: September 15, 2020
• First Submitted That Met QC Criteria: September 15, 2020
• First Posted (Actual): September 21, 2020

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 27, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Inflammatory Bowel Disease
• 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: GB004-2101; 2020-002306-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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