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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-001430-33 | EudraCT Number |
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Sponsor terminated the study since a new molecular entity was able to achieve greater target coverage
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tilpisertib 300 mg | Experimental | Participants will receive blinded tilpisertib 300 mg for up to 10 weeks. An efficacy assessment will be performed at Week 10. Participants who achieve MCS response will continue on the blinded treatment for up to 50 weeks. |
|
| Tilpisertib 100 mg | Experimental | Participants will receive blinded tilpisertib 100 mg for up to 10 weeks. An efficacy assessment will be performed at Week 10. Participants who achieve MCS response will continue on the blinded treatment for up to 50 weeks. |
|
| Placebo | Placebo Comparator | Participants will receive blinded tilpisertib matching placebo for up to 10 weeks. An efficacy assessment will be performed at Week 10. Participants who achieve MCS response will continue on the blinded treatment for up to 50 weeks. |
|
| Open-label Tilpisertib 300 mg | Experimental | Based on the efficacy assessment results at Week 10, participants who do not achieve MCS response will have the option to receive open-label tilpisertib 300 mg for up to 50 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tilpisertib | Drug | Tablets administered orally once daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
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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 (TNFα) 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.
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:
Laboratory assessments at screening within the following parameters:
Key Exclusion Criteria:
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Gilead Study Director | Gilead Sciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Gut P.C., dba Digestive Health Specialists of the Southeast | Dothan | Alabama | 36305 | United States | ||
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32 participants were screened.
Participants were enrolled at study sites in Australia, Europe and the United States.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tilpisertib 300 mg (Blinded Treatment Phase) | Tilpisertib 300 mg tablet orally once daily up to Week 10. Participants who achieved clinical response per Modified Mayo Clinic score (MCS) at Week 10, continued to receive tilpisertib 300 mg tablets orally once daily for a maximum of 50 weeks in the Blinded Treatment phase. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Blinded Treatment Phase |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 19, 2020 | Jun 9, 2022 |
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| Placebo | Drug | Tablets administered orally once daily |
|
| Week 10 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Om Research LLC |
| Lancaster |
| California |
| 93534 |
| United States |
| United Medical Doctors | Murrieta | California | 92563 | United States |
| Alliance Clinical Research | Poway | California | 92064 | United States |
| Alliance Medical Research | Coral Springs | Florida | 33071 | United States |
| Encore Borland-Groover Clinical Research | Jacksonville | Florida | 32256 | United States |
| A Plus Research, Inc | Miami | Florida | 33144 | United States |
| BRCR Medical Center Inc. | Plantation | Florida | 33322 | United States |
| Advanced Medical Research Center | Port Orange | Florida | 32127 | United States |
| Gastrointestinal Specialists of Georgia | Marietta | Georgia | 30060 | United States |
| Atlanta Gastroenterology Specialists, PC | Suwanee | Georgia | 30024 | United States |
| Louisiana Research Center, LLC | Shreveport | Louisiana | 71105 | United States |
| Kansas City Research Institute | Kansas City | Missouri | 64131 | United States |
| Advanced Biomedical Research of America | Las Vegas | Nevada | 89123 | United States |
| Consultants for Clinical Research | Cincinnati | Ohio | 45219 | United States |
| Gastroenterology Associates of Orangeburg | Orangeburg | South Carolina | 29118 | United States |
| Vanderbilt University Medical Center - IBD Clinic | Nashville | Tennessee | 37212-1375 | United States |
| Allied Digestive Disease Center | Cypress | Texas | 77429 | United States |
| Southwest Clinical Trials | Houston | Texas | 77074 | United States |
| Clinical Associates in Research Therapeutics of America, LLC | San Antonio | Texas | 78212 | United States |
| Texas Digestive Disease Consultants | San Marcos | Texas | 78666 | United States |
| Texas Digestive Disease Consultants | Southlake | Texas | 76092 | United States |
| Allegiance Research Specialists, LLC | Wauwatosa | Wisconsin | 53225 | United States |
| Coastal Digestive Health | Maroochydore | Queensland | 4558 | Australia |
| The Queen Elizabeth Hospital | Woodville | South Australia | 5011 | Australia |
| St Vincent's Hospital Melbourne | Fitzroy | Victoria | 3065 | Australia |
| Emeritus Research | Melbourne | Victoria | 3124 | Australia |
| Medizinische Universität Innsbruck, Universitätsklinik für Innere Medizin I | Innsbruck | 6020 | Austria |
| Medizinische Universitat Wien Klinik fur Innere Medizin III/Abt. fur Gastroenterologie and Hepatologie | Vienna | 1090 | Austria |
| Vancouver General Hospital - The Gordon and Leslie Diamond Health Care Centre | Vancouver | British Columbia | V5Z 1M9 | Canada |
| Hopital Beaujon | Clichy | 92110 | France |
| CHU de Dijon Bourgogne | Dijon | 21079 | France |
| Centre Hospitalier Universitaire de Grenoble Alpes | Grenoble | 38043 | France |
| CHRU de Lille - Hôpital Claude Huriez | Lille | 59000 | France |
| CHU de Lyon Sud | Pierre-Bénite | 69495 | France |
| CHRU Pontchaillou | Rennes | 35033 Cedex 9 | France |
| CHU de Saint Etienne | Saint-Etienne | 42055 | France |
| Hopital Rangueil | Toulouse | 31059 cedex 9 | France |
| CHRU de Nancy | Vandœuvre-lès-Nancy | 54511 | France |
| Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik fur Innere Medizin I, Haus C, Haus K3 | Kiel | 24105 | Germany |
| Eugastro GmbH | Leipzig | 04103 | Germany |
| Gastroenterologische Gemeinschaftspraxis Minden | Minden | 32423 | Germany |
| Istituto Clinico Humanitas | Rozzano | 20089 | Italy |
| Twoja Przychodnia - Szczecinskie Centrum Medyczne | Szczecin | 71-434 | Poland |
| "GASTROMED" Kopon, Zmudzinski i Wsp. Sp. J. Spec. Centrum Gastrologii i Endoskopii, Spec. Gabinety Lekarskie | Torun | 87-100 | Poland |
| Centrum Medyczne Melita Medical | Wroclaw | 50-449 | Poland |
| Gastroenterologische Praxis Balsiger, Seibold & Partner/Crohn-Colitis-Zentrum | Bern | 3012 | Switzerland |
| Inselspital Bern/Klinik fur Viszerale Chirurgie und Medizin/Bauchzentrum | Bern | CH-3010 | Switzerland |
| Universitätsspital Zürich/Klinik für Gastroenterologie und Hepatologie | Zurich | 8091 | Switzerland |
| Tilpisertib 100 mg (Blinded Treatment Phase) |
Tilpisertib 100 mg tablet orally once daily up to Week 10. Participants who achieved clinical response per modified MCS at Week 10, continued to receive tilpisertib 100 mg tablets orally once daily for a maximum of 50 weeks in the Blinded Treatment phase. |
| FG002 | Placebo (Blinded Treatment Phase) | Placebo tablet orally once daily up to Week 10. Participants who achieved clinical response per modified MCS at Week 10, continued to receive placebo tablets orally once daily for a maximum of 50 weeks in the Blinded Treatment phase. |
| FG003 | Tilpisertib 300 mg From Tilpisertib 300 mg (Open-label Treatment Phase) | Participants who received tilpisertib 300 mg and did not achieve clinical response per modified MCS at Week 10 in the Blinded Treatment phase, received tilpisertib 300 mg tablets orally once daily for up to 50 weeks in the Open-label Treatment phase. |
| FG004 | Tilpisertib 300 mg From Tilpisertib 100 mg (Open-label Treatment Phase) | Participants who received tilpisertib 100 mg and did not achieve clinical response per modified MCS at Week 10 in the Blinded Treatment phase, received tilpisertib 300 mg tablets orally once daily for up to 50 weeks in the Open-label Treatment phase. |
| FG005 | Tilpisertib 300 mg From Placebo (Open-label Treatment Phase) | Participants who received placebo and did not achieve clinical response per modified MCS at Week 10 in the Blinded Treatment phase, received tilpisertib 300 mg tablets orally once daily for up to 50 weeks in the Open-label Treatment phase. |
| COMPLETED |
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| NOT COMPLETED |
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|
| Open-label Treatment Phase |
|
|
Safety Analysis Set included all participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Tilpisertib 300 mg (Blinded Treatment Phase) | Tilpisertib 300 mg tablet orally once daily up to Week 10. Participants who achieved clinical response per modified MCS at Week 10, continued to receive tilpisertib 300 mg tablets orally once daily for a maximum of 50 weeks in the Blinded Treatment phase. |
| BG001 | Tilpisertib 100 mg (Blinded Treatment Phase) | Tilpisertib 100 mg tablet orally once daily up to Week 10. Participants who achieved clinical response per modified MCS at Week 10, continued to receive tilpisertib 100 mg tablets orally once daily for a maximum of 50 weeks in the Blinded Treatment phase. |
| BG002 | Placebo (Blinded Treatment Phase) | Placebo tablet orally once daily up to Week 10. Participants who achieved clinical response per modified MCS at Week 10, continued to receive placebo tablets orally once daily for a maximum of 50 weeks in the Blinded Treatment phase. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Not Permitted means local regulators did not allow collection of race information. | Count of Participants | Participants |
| |||||||||||||||
| Race/Ethnicity, Customized | Not Permitted means local regulators did not allow collection of ethnicity information. | Count of Participants | Participants |
| |||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Full analysis set included all randomized participants who received at least 1 dose of study drug. | Posted | Number | percentage of participants | Week 10 |
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| 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). | Participants in the Full Analysis Set were analyzed. | Posted | Number | percentage of participants | Week 10 |
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| 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. | Participants in the Full Analysis Set were analyzed. | Posted | Number | percentage of participants | Week 10 |
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| 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. | Participants in the Full Analysis Set were analyzed. | Posted | Number | percentage of participants | Week 10 |
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| 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. | Participants in the Full Analysis Set with at least 1 histological assessment were analyzed. | Posted | Number | percentage of participants | Week 10 |
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| 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. | Safety Analysis Set included all participants who received at least one dose of study drug. | Posted | Number | percentage of participants | 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 |
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| 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. | Participants in the Safety Analysis Set were analyzed. | Posted | Number | percentage of participants | 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 |
|
Adverse Events: Blinded Treatment phase: First dose date up to 50.6 weeks plus 30 days; Open-label Treatment phase: First dose date up to 50.7 weeks plus 30 days; All-Cause Mortality: Enrollment up to Week 70.3
Adverse Events: Safety Analysis Set included all participants who received at least one dose of study drug; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tilpisertib 300 mg (Blinded Treatment Phase) | Tilpisertib 300 mg tablet orally once daily up to Week 10. Participants who achieved clinical response per modified MCS at Week 10, continued to receive tilpisertib 300 mg tablets orally once daily for a maximum of 50 weeks in the Blinded Treatment phase. | 0 | 7 | 1 | 7 | 4 | 7 |
| EG001 | Tilpisertib 100 mg (Blinded Treatment Phase) | Tilpisertib 100 mg tablet orally once daily up to Week 10. Participants who achieved clinical response per modified MCS at Week 10, continued to receive tilpisertib 100 mg tablets orally once daily for a maximum of 50 weeks in the Blinded Treatment phase. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG002 | Placebo (Blinded Treatment Phase) | Placebo tablet orally once daily up to Week 10. Participants who achieved clinical response per modified MCS at Week 10, continued to receive placebo tablets orally once daily for a maximum of 50 weeks in the Blinded Treatment phase. | 0 | 6 | 1 | 6 | 2 | 6 |
| EG003 | Tilpisertib 300 mg From Tilpisertib 300 mg (Open-label Treatment Phase) | Participants who received tilpisertib 300 mg and did not achieve clinical response per modified MCS at Week 10 in the Blinded Treatment phase, received tilpisertib 300 mg tablets orally once daily for up to 50 weeks in the Open-label Treatment phase. | 0 | 4 | 0 | 4 | 2 | 4 |
| EG004 | Tilpisertib 300 mg From Tilpisertib 100 mg (Open-label Treatment Phase) | Participants who received tilpisertib 100 mg and did not achieve clinical response per modified MCS at Week 10 in the Blinded Treatment phase, received tilpisertib 300 mg tablets orally once daily for up to 50 weeks in the Open-label Treatment phase. | 0 | 3 | 0 | 3 | 2 | 3 |
| EG005 | Tilpisertib 300 mg From Placebo (Open-label Treatment Phase) | Participants who received placebo and did not achieve clinical response per modified MCS at Week 10 in the Blinded Treatment phase, received tilpisertib 300 mg tablets orally once daily for up to 50 weeks in the Open-label Treatment phase. | 0 | 3 | 0 | 3 | 2 | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Proctalgia | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Campylobacter infection | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| External ear inflammation | Ear and labyrinth disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Colitis ulcerative | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Haemorrhoids thrombosed | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Seasonal allergy | Immune system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Asymptomatic COVID-19 | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Hordeolum | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Mastitis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Iron deficiency | Metabolism and nutrition disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Vitamin B12 deficiency | Metabolism and nutrition disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Vitamin D deficiency | Metabolism and nutrition disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Erectile dysfunction | Reproductive system and breast disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
|
Gilead made the decision to discontinue the development of tilpisertib since a new molecular entity was able to achieve greater target coverage. The decision was not due to any safety concerns. Since only 19 participants were enrolled, none of the planned statistical analyses were performed. During the coronavirus disease 2019 (COVID-19) pandemic, there were changes to protocol visits and procedures where necessary to mitigate the impact of the pandemic to the study.
After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gilead Clinical Study Information Center | Gilead Sciences | 1-833-445-3230 (GILEAD-0) | GileadClinicalTrials@gilead.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 5, 2021 | Jun 9, 2022 | SAP_001.pdf |
| ID | Term |
|---|---|
| D003093 | Colitis, Ulcerative |
| ID | Term |
|---|---|
| D003092 | Colitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D015212 | Inflammatory Bowel Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
Not provided
Not provided
| Disease worsening |
|
| Investigator's decision |
|
| Lost to Follow-up |
|
| MCS response not achieved at open-label week 10 |
|
| Male |
|
| Asian |
|
| Black or African American |
|
| Native Hawaiian or Other Pacific Islander |
|
| White |
|
| Other |
|
| Not Permitted |
|
| Hispanic or Latino |
|
| Not Permitted |
|
| United States |
|
| Australia |
|
| Switzerland |
|
| Germany |
|
Placebo tablet orally once daily up to Week 10. Participants who achieved clinical response per modified MCS at Week 10, continued to receive placebo tablets orally once daily for a maximum of 50 weeks in the Blinded Treatment phase. |
|
|
| OG002 | Placebo (Blinded Treatment Phase) | Placebo tablet orally once daily up to Week 10. Participants who achieved clinical response per modified MCS at Week 10, continued to receive placebo tablets orally once daily for a maximum of 50 weeks in the Blinded Treatment phase. |
|
|
| OG002 | Placebo (Blinded Treatment Phase) | Placebo tablet orally once daily up to Week 10. Participants who achieved clinical response per modified MCS at Week 10, continued to receive placebo tablets orally once daily for a maximum of 50 weeks in the Blinded Treatment phase. |
|
|
| Tilpisertib 100 mg (Blinded Treatment Phase) |
Tilpisertib 100 mg tablet orally once daily up to Week 10. Participants who achieved clinical response per modified MCS at Week 10, continued to receive tilpisertib 100 mg tablets orally once daily for a maximum of 50 weeks in the Blinded Treatment phase. |
| OG002 | Placebo (Blinded Treatment Phase) | Placebo tablet orally once daily up to Week 10. Participants who achieved clinical response per modified MCS at Week 10, continued to receive placebo tablets orally once daily for a maximum of 50 weeks in the Blinded Treatment phase. |
|
|
| OG001 | Tilpisertib 100 mg (Blinded Treatment Phase) | Tilpisertib 100 mg tablet orally once daily up to Week 10. Participants who achieved clinical response per modified MCS at Week 10, continued to receive tilpisertib 100 mg tablets orally once daily for a maximum of 50 weeks in the Blinded Treatment phase. |
| OG002 | Placebo (Blinded Treatment Phase) | Placebo tablet orally once daily up to Week 10. Participants who achieved clinical response per modified MCS at Week 10, continued to receive placebo tablets orally once daily for a maximum of 50 weeks in the Blinded Treatment phase. |
| OG003 | Tilpisertib 300 mg From Tilpisertib 300 mg (Open-label Treatment Phase) | Participants who received tilpisertib 300 mg and did not achieve clinical response per modified MCS at Week 10 in the Blinded Treatment phase, received tilpisertib 300 mg tablets orally once daily for up to 50 weeks in the Open-label Treatment phase. |
| OG004 | Tilpisertib 300 mg From Tilpisertib 100 mg (Open-label Treatment Phase) | Participants who received tilpisertib 100 mg and did not achieve clinical response per modified MCS at Week 10 in the Blinded Treatment phase, received tilpisertib 300 mg tablets orally once daily for up to 50 weeks in the Open-label Treatment phase. |
| OG005 | Tilpisertib 300 mg From Placebo (Open-label Treatment Phase) | Participants who received placebo and did not achieve clinical response per modified MCS at Week 10 in the Blinded Treatment phase, received tilpisertib 300 mg tablets orally once daily for up to 50 weeks in the Open-label Treatment phase. |
|
|
| OG001 |
| Tilpisertib 100 mg (Blinded Treatment Phase) |
Tilpisertib 100 mg tablet orally once daily up to Week 10. Participants who achieved clinical response per modified MCS at Week 10, continued to receive tilpisertib 100 mg tablets orally once daily for a maximum of 50 weeks in the Blinded Treatment phase. |
| OG002 | Placebo (Blinded Treatment Phase) | Placebo tablet orally once daily up to Week 10. Participants who achieved clinical response per modified MCS at Week 10, continued to receive placebo tablets orally once daily for a maximum of 50 weeks in the Blinded Treatment phase. |
| OG003 | Tilpisertib 300 mg From Tilpisertib 300 mg (Open-label Treatment Phase) | Participants who received tilpisertib 300 mg and did not achieve clinical response per modified MCS at Week 10 in the Blinded Treatment phase, received tilpisertib 300 mg tablets orally once daily for up to 50 weeks in the Open-label Treatment phase. |
| OG004 | Tilpisertib 300 mg From Tilpisertib 100 mg (Open-label Treatment Phase) | Participants who received tilpisertib 100 mg and did not achieve clinical response per modified MCS at Week 10 in the Blinded Treatment phase, received tilpisertib 300 mg tablets orally once daily for up to 50 weeks in the Open-label Treatment phase. |
| OG005 | Tilpisertib 300 mg From Placebo (Open-label Treatment Phase) | Participants who received placebo and did not achieve clinical response per modified MCS at Week 10 in the Blinded Treatment phase, received tilpisertib 300 mg tablets orally once daily for up to 50 weeks in the Open-label Treatment phase. |
|
|