Study to Evaluate the Efficacy and Safety of Tilpisertib in Adults With Moderately to Severely Active Ulcerative Colitis

Ulcerative Colitis Clinical Trial

— Falcon  

Official title:

A Phase 2, Blinded, Randomized, Placebo-Controlled Study Evaluating the Efficacy and Safety of GS-4875 in Subjects With Moderately to Severely Active Ulcerative Colitis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04130919
• Other study ID #: GS-US-365-4237
• Secondary ID: 2019-001430-33
• Status: Terminated
• Phase: Phase 2
• Start date: December 20, 2019
• Est. completion date: December 14, 2021

Study information

• Verified date: July 2022
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to demonstrate the efficacy of tilpisertib (formerly GS-4875) compared with placebo control in achieving clinical remission per modified Mayo Clinic Score (MCS) in adults with moderately to severely active ulcerative colitis (UC).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: December 14, 2021
• Est. primary completion date: February 25, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Males, or non-pregnant, non-lactating females, at least 18 years of age based on the date of the screening visit.
• UC of at least 3 months duration before randomization confirmed by endoscopy and histology at any time in the past AND a minimum disease extent of 15 centimeter (cm) from the anal verge. Documentation of endoscopy and histology consistent with the diagnosis of UC must be available in the source documents prior to the initiation of screening.
• Moderately to severely active UC as determined during screening by a centrally read endoscopy score = 2, a Rectal Bleeding subscore = 1, a Stool Frequency subscore = 1 and Physicians Global Assessment (PGA) of = 2 as defined by the Mayo Clinic Score; total MCS must be between 6 and 12, inclusive.
• Previously demonstrated an inadequate response (primary non-response) or loss of response (secondary non-response) to a tumor necrosis factor-alpha (TNFa) inhibitor (ie, infliximab, adalimumab, golimumab, or biosimilars). The induction treatment regimen resulting in inadequate response or loss of response should have been in accordance with local prescribing information/guidelines or as outlined below.
• Infliximab: 5 mg/kg at Weeks 0, 2, and 6
• Adalimumab: 160 mg on Day 1 (given in 1 day or split over consecutive days), followed by 80 mg 2 weeks later (Day 15), 40 mg 2 weeks later (Day 29) and every 2 weeks thereafter until Day 57
• Golimumab: 200 mg on Day 1 followed by 100 mg at Week 2
• May be receiving concomitant therapy for UC at the time of enrollment as specified in the protocol, provided the dose prescribed has been stable as indicated prior to randomization.
• Meet the following Tuberculosis (TB) screening criteria:
• No evidence of active TB, latent TB, or inadequately treated TB as evidenced by 1

of the following:

• A negative QuantiFERON test or equivalent assay reported by the central lab at screening or within 90 days prior to randomization date. OR
• A history of fully treated active or latent TB according to local standard of care. Investigator must verify adequate previous anti-TB treatment and provide documentation; these individuals do not require QuantiFERON testing and eligibility must be approved by the sponsor prior to enrollment in the study. AND
• A chest radiograph (views as per local guidelines with the report or films available for investigator review) taken at screening or within the 4 months prior to randomization without evidence of active or latent TB infection.
• Laboratory assessments at screening within the following parameters:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and total bilirubin = 2 X upper limit of normal (ULN)
• Estimated glomerular filtration rate (eGFR) = 60 ml/min (1.0 mL/sec) as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Cystatin C formula as described in protocol.
• Hemoglobin = 8 g/dL (= 80 g/L)
• Absolute neutrophil count (ANC) = 1.5 × 10^3/µL (= 1.5 GI/L)
• Platelets = 100 × 10^3/µL (= 100 GI/L)
• White blood cells (WBC) = 3 × 10^3/µL (= 3 GI/L)
• Absolute lymphocyte count = 0.75 × 10^3/µL (= 0.75 GI/L)

Key Exclusion Criteria:

• Currently displaying clinical signs of acute severe colitis, fulminant colitis, or toxic megacolon. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Tilpisertib
Tablets administered orally once daily
• Placebo
Tablets administered orally once daily

Locations

Country	Name	City	State
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Coastal Digestive Health	Maroochydore	Queensland
Australia	Emeritus Research	Melbourne	Victoria
Australia	The Queen Elizabeth Hospital	Woodville	South Australia
Austria	Medizinische Universität Innsbruck, Universitätsklinik für Innere Medizin I	Innsbruck
Austria	Medizinische Universitat Wien Klinik fur Innere Medizin III/Abt. fur Gastroenterologie and Hepatologie	Vienna
Canada	Vancouver General Hospital - The Gordon and Leslie Diamond Health Care Centre	Vancouver	British Columbia
France	Hopital Beaujon	Clichy
France	CHU de Dijon Bourgogne	Dijon
France	Centre Hospitalier Universitaire de Grenoble Alpes	Grenoble
France	CHRU de Lille - Hôpital Claude Huriez	Lille
France	CHU de Lyon Sud	Pierre-Benite
France	CHRU Pontchaillou	Rennes
France	CHU de Saint Etienne	Saint-Etienne
France	Hopital Rangueil	Toulouse
France	CHRU de Nancy	Vandoeuvre-les-Nancy Cedex
Germany	Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik fur Innere Medizin I, Haus C, Haus K3	Kiel
Germany	Eugastro GmbH	Leipzig
Germany	Gastroenterologische Gemeinschaftspraxis Minden	Minden
Italy	Istituto Clinico Humanitas	Rozzano
Poland	Twoja Przychodnia - Szczecinskie Centrum Medyczne	Szczecin
Poland	"GASTROMED" Kopon, Zmudzinski i Wsp. Sp. J. Spec. Centrum Gastrologii i Endoskopii, Spec. Gabinety Lekarskie	Torun
Poland	Centrum Medyczne Melita Medical	Wroclaw
Switzerland	Gastroenterologische Praxis Balsiger, Seibold & Partner/Crohn-Colitis-Zentrum	Bern
Switzerland	Inselspital Bern/Klinik fur Viszerale Chirurgie und Medizin/Bauchzentrum	Bern
Switzerland	Universitätsspital Zürich/Klinik für Gastroenterologie und Hepatologie	Zurich
United States	Consultants for Clinical Research	Cincinnati	Ohio
United States	Alliance Medical Research	Coral Springs	Florida
United States	Allied Digestive Disease Center	Cypress	Texas
United States	Gut P.C., dba Digestive Health Specialists of the Southeast	Dothan	Alabama
United States	Southwest Clinical Trials	Houston	Texas
United States	Encore Borland-Groover Clinical Research	Jacksonville	Florida
United States	Kansas City Research Institute	Kansas City	Missouri
United States	Om Research LLC	Lancaster	California
United States	Advanced Biomedical Research of America	Las Vegas	Nevada
United States	Gastrointestinal Specialists of Georgia	Marietta	Georgia
United States	A Plus Research, Inc	Miami	Florida
United States	United Medical Doctors	Murrieta	California
United States	Vanderbilt University Medical Center - IBD Clinic	Nashville	Tennessee
United States	Gastroenterology Associates of Orangeburg	Orangeburg	South Carolina
United States	BRCR Medical Center Inc.	Plantation	Florida
United States	Advanced Medical Research Center	Port Orange	Florida
United States	Alliance Clinical Research	Poway	California
United States	Clinical Associates in Research Therapeutics of America, LLC	San Antonio	Texas
United States	Texas Digestive Disease Consultants	San Marcos	Texas
United States	Louisiana Research Center, LLC	Shreveport	Louisiana
United States	Texas Digestive Disease Consultants	Southlake	Texas
United States	Atlanta Gastroenterology Specialists, PC	Suwanee	Georgia
United States	Allegiance Research Specialists, LLC	Wauwatosa	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  France,  Germany,  Italy,  Poland,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Achieved Clinical Remission Per Modified Mayo Clinic Score (MCS) at Week 10	The modified MCS is a scoring system for assessment of ulcerative colitis (UC) activity and is composed of subscores from endoscopy (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]), rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 or more stools more than normal), and physician's global assessment (PGA) (range: 0 to 3, where 0 = normal and 3 = severe disease). Total score for MCS ranges from 0 to 12 (sum of all subscores), with higher scores indicating higher disease activity. Clinical remission per modified MCS is defined as stool frequency subscore = 1 and not greater than baseline, rectal bleeding subscore of 0, and endoscopic subscore = 1 at Week 10.	Week 10
Secondary	Percentage of Participants Who Achieved Endoscopic Response at Week 10	Endoscopic response was defined as an endoscopic subscore of = 1 at Week 10. Endoscopic subscore is a part of the modified MCS which is a scoring system for assessment of UC activity. Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease, 1 = mild disease (erythema, decreased vascular pattern), 2 = moderate disease (marked erythema, lack of vascular pattern, friability, erosions), and 3 = severe disease (spontaneous bleeding, ulceration).	Week 10
Secondary	Percentage of Participants Who Achieved MCS Response at Week 10	The modified MCS is a scoring system for assessment of UC activity and is composed of subscores from endoscopy (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]), rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 or more stools more than normal), and PGA (range: 0 to 3, where 0 = normal and 3 = severe disease). Total score for MCS ranges from 0 to 12 (sum of all subscores), with higher scores indicating higher disease activity. MCS response is defined as a decrease from baseline of = 3 points and at least 30% in MCS, in addition to a = 1 point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore = 1 at Week 10.	Week 10
Secondary	Percentage of Participants Who Achieved MCS Remission at Week 10	The modified MCS is a scoring system for assessment of UC activity and is composed of subscores from endoscopy (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]), rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 or more stools more than normal), and PGA (range: 0 to 3, where 0 = normal and 3 = severe disease). Total score for MCS ranges from 0 to 12 (sum of all subscores), with higher scores indicating higher disease activity. MCS remission is defined as a MCS score of = 2 and no individual subscore > 1 at Week 10.	Week 10
Secondary	Percentage of Participants Who Achieved Histologic Remission Based Upon the Geboes Scale at Week 10	Geboes histologic remission was assessed using the Geboes histologic scores to identify histologic changes in ulcerative colitis. Possible scores are Grade 0:Architectural changes(0.0=No abnormality to 0.3=Severe diffuse or multifocal abnormalities); Grade 1:Chronic inflammatory infiltrate(1.0=No increase to 1.3=Marked increase);Grade 2A:Eosinophils in lamina propria(2A.0=No increase to 2A.3-=Marked increase; Grade 2B:Neutrophils in lamina propria(2B.0= No increase to 2B.3=Marked increase);Grade 3:Neutrophils in epithelium (3.0=None to 3.3=>50% crypts involved);Grade 4:Crypt destruction(4.0=none to 4.3=Unequivocal crypt destruction),and Grade 5:Erosions and ulcerations:(5.0=No erosion, ulceration or granulation to 5.4=Ulcer or granulation tissue). Histologic remission defined as having Grade 0 of = 0.3, Grade 1 of = 1.1, Grade 2a of = 2A.3, Grade 2b of 2B.0, Grade 3 of 3.0, Grade 4 of 4.0, and Grade 5 of 5.0. Geboes score ranges from 0 to 5.4. Lower values indicate better outcome.	Week 10
Secondary	Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)	Treatment-emergent adverse events (TEAEs) for the Blinded Treatment phase are either defined as AEs with an onset date on or after the Blinded Treatment phase study drug start date and no later than 30 days after permanent discontinuation of the Blinded Treatment phase study drug if no Open-label Treatment phase study drug was taken, or any AEs with an onset date on or after the Blinded Treatment phase study drug start date and before the Open-label Treatment phase study drug start date if Open-label Treatment phase study drug was taken and/or any AEs leading to premature discontinuation of Blinded Treatment phase study drug. TEAEs for the Open-label Treatment phase are either defined as AEs with an onset date on or after the Open-label Treatment phase study drug start date and no later than 30 days after permanent discontinuation of the Open-lab Treatment phase study drug and/or any AEs leading to premature discontinuation of Open-label Treatment phase study drug.	Blinded Treatment phase: First dose date up to 50.6 weeks plus 30 days; Open-label phase: First dose date up to 50.7 weeks plus 30 days
Secondary	Percentage of Participants Who Experienced Laboratory Abnormalities	Treatment-emergent laboratory abnormalities for Blinded Treatment phase are defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of Blinded Treatment phase study drug plus 30 days for participants who permanently discontinued Blinded Treatment phase study drug or before the first dose of Open-label Treatment phase study drug. For the Open-label Treatment phase, treatment-emergent laboratory abnormalities are defined as values that increase at least 1 toxicity grade from Open-label baseline at any postbaseline time point, up to and including the date of last dose of Open-label Treatment phase study drug plus 30 days for participants who permanently discontinued Open-label phase study drug. For maximum postbaseline toxicity grade, the most severe graded abnormality from all tests was counted for each patient. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening.	Blinded Treatment phase: First dose date up to 50.6 weeks plus 30 days; Open-label phase: First dose date up to 50.7 weeks plus 30 days