Clinical Trials List
Protocol NumberGS-US-326-1100
NCT Number(ClinicalTrials.gov Identfier)NCT02520284
2016-02-01 - 2017-09-14
Phase II/III
Terminated5
ICD-10K51
Ulcerative colitis
ICD-9556.9
Ulcerative colitis, unspecified
A Combined Phase 2/3, Double-Blind, Randomized, Placebo-Controlled, Induction and Maintenance Study Evaluating the Safety and Efficacy of GS-5745 in Subjects with Moderately to Severely Active Ulcerative Colitis
-
Trial Applicant
GILEAD SCIENCES HONG KONG LIMITED
-
Sponsor
Gilead Sciences, Inc
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- 許振銘 無
- 林偉彬 無
- 林淳榮 無
- 朱允義 無
- Ming-Yao Su 無
- Chia-Jung Kuo 無
- 何玉彬 無
- Wen-Sy Tsai 無
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
Moderately to Severely Active Ulcerative Colitis
Objectives
The primary objectives of this study are as follows: 1) To evaluate the efficacy of andecaliximab to induce endoscopy, rectal bleeding, and stool frequency (EBS) clinical remission at Week 8 (Cohort 1); 2) To evaluate the efficacy of andecaliximab to maintain EBS clinical remission at Week 52 (Cohort 2); and 3) To evaluate the safety and tolerability of andecaliximab. The study will consist of 3 parts: Induction Phase (Cohort 1), Maintenance Phase (Cohort 2), and an optional Extended Treatment Phase.
Test Drug
GS-5745
Active Ingredient
GS-5745
Dosage Form
Injction
Dosage
150
Endpoints
Primary Outcome Measures :
1. For Cohort 1, Percentage of Participants With EBS Clinical Remission at Week 8 [ Time Frame: Week 8 ]
EBS clinical remission was defined as an endoscopic subscore of 0 or 1 (endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]); rectal bleeding subscore of 0 (rectal bleeding subscore range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes); and at least a 1-point decrease in stool frequency from baseline to achieve a subscore of 0 or 1 (stool frequency subscore range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 stools more than normal).
Secondary Outcome Measures :
1. For Cohort 1, Percentage of Participants With MCS Remission at Week 8 [ Time Frame: Week 8 ]
The MCS was 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 stools more than normal), and physician's global assessment (PGA). The PGA acknowledged the participant's daily recollection of abdominal discomfort and general sense of wellbeing, and other observations, such as physical findings and the participant's performance status. The PGA score ranged from 0 to 3 with higher score indicating the severe disease. The MCS remission was defined as a MCS of ≤ 2 points and no individual subscore > 1 point. Total score for MCS ranged from 0 to 12 (sum of all subscores), with higher scores indicating disease worsening.
2. For Cohort 1, Percentage of Participants With MCS Response at Week 8 [ Time Frame: Week 8 ]
The MCS was 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 stools more than normal), and PGA. The PGA acknowledged the participant's daily recollection of abdominal discomfort and general sense of wellbeing, and other observations, such as physical findings and the participant's performance status. The PGA score ranged from 0 to 3 with higher score indicating the severe disease. Total score for MCS ranged from 0 to 12 (sum of all subscores), with higher scores indicating disease worsening. The MCS response was defined as a MCS reduction of ≥ 3 points and at least 30% from baseline, with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of 0 or 1.
3. For Cohort 1, Percentage of Participants With Endoscopic Remission at Week 8 [ Time Frame: Week 8 ]
Endoscopic remission was defined as endoscopic subscore of 0. Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration).
4. For Cohort 1, Percentage of Participants With Endoscopic Response at Week 8 [ Time Frame: Week 8 ]
Endoscopic response was defined as endoscopic subscore of 0 or 1. Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration).
5. For Cohort 1, Percentage of Participants With Mucosal Healing as Determined by the Geboes Histologic Scoring System at Week 8 [ Time Frame: Week 8 ]
Mucosal healing was defined as elimination of ulcers/erosion, elimination of crypt destruction, elimination of intraepithelial neutrophils, elimination of lamina propria neutrophils, and reduction in lamina propria chronic inflammatory cells to at most a mild increase. When measured by the Geboes histologic scoring system, it was the selection of the following combined scores of ≤ 3 for Grade 0 (Structural Architectural Change), ≤ 1 for Grade 1 (Chronic Inflammatory Infiltrate), ≤ 3 for Grade 2A (Lamina Propria Eosinophils), and 0 for Grade 2B (Lamina Propria Neutrophils), Grade 3 (Neutrophils in Epithelium), Grade 4 (Crypt Destruction), and Grade 5 (Erosion or Ulceration). Total Geboes histologic score ranged from 0 to 22, with higher scores indicating greater disease severity.
6. For Cohort 1, Percentage of Participants With MCS Remission (Alternative Definition) at Week 8 [ Time Frame: Week 8 ]
The MCS remission (alternative definition) was defined as a 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 stools more than normal), and PGA subscore (range: 0 to 3 with higher score indicating the severe disease) of 0, and an endoscopic subscore (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]) of 0 or 1 for an overall MCS of ≤ 1. Total score for MCS ranged from 0 to 12 (sum of all subscores), with higher scores indicating disease worsening.
1. For Cohort 1, Percentage of Participants With EBS Clinical Remission at Week 8 [ Time Frame: Week 8 ]
EBS clinical remission was defined as an endoscopic subscore of 0 or 1 (endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]); rectal bleeding subscore of 0 (rectal bleeding subscore range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes); and at least a 1-point decrease in stool frequency from baseline to achieve a subscore of 0 or 1 (stool frequency subscore range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 stools more than normal).
Secondary Outcome Measures :
1. For Cohort 1, Percentage of Participants With MCS Remission at Week 8 [ Time Frame: Week 8 ]
The MCS was 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 stools more than normal), and physician's global assessment (PGA). The PGA acknowledged the participant's daily recollection of abdominal discomfort and general sense of wellbeing, and other observations, such as physical findings and the participant's performance status. The PGA score ranged from 0 to 3 with higher score indicating the severe disease. The MCS remission was defined as a MCS of ≤ 2 points and no individual subscore > 1 point. Total score for MCS ranged from 0 to 12 (sum of all subscores), with higher scores indicating disease worsening.
2. For Cohort 1, Percentage of Participants With MCS Response at Week 8 [ Time Frame: Week 8 ]
The MCS was 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 stools more than normal), and PGA. The PGA acknowledged the participant's daily recollection of abdominal discomfort and general sense of wellbeing, and other observations, such as physical findings and the participant's performance status. The PGA score ranged from 0 to 3 with higher score indicating the severe disease. Total score for MCS ranged from 0 to 12 (sum of all subscores), with higher scores indicating disease worsening. The MCS response was defined as a MCS reduction of ≥ 3 points and at least 30% from baseline, with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of 0 or 1.
3. For Cohort 1, Percentage of Participants With Endoscopic Remission at Week 8 [ Time Frame: Week 8 ]
Endoscopic remission was defined as endoscopic subscore of 0. Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration).
4. For Cohort 1, Percentage of Participants With Endoscopic Response at Week 8 [ Time Frame: Week 8 ]
Endoscopic response was defined as endoscopic subscore of 0 or 1. Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration).
5. For Cohort 1, Percentage of Participants With Mucosal Healing as Determined by the Geboes Histologic Scoring System at Week 8 [ Time Frame: Week 8 ]
Mucosal healing was defined as elimination of ulcers/erosion, elimination of crypt destruction, elimination of intraepithelial neutrophils, elimination of lamina propria neutrophils, and reduction in lamina propria chronic inflammatory cells to at most a mild increase. When measured by the Geboes histologic scoring system, it was the selection of the following combined scores of ≤ 3 for Grade 0 (Structural Architectural Change), ≤ 1 for Grade 1 (Chronic Inflammatory Infiltrate), ≤ 3 for Grade 2A (Lamina Propria Eosinophils), and 0 for Grade 2B (Lamina Propria Neutrophils), Grade 3 (Neutrophils in Epithelium), Grade 4 (Crypt Destruction), and Grade 5 (Erosion or Ulceration). Total Geboes histologic score ranged from 0 to 22, with higher scores indicating greater disease severity.
6. For Cohort 1, Percentage of Participants With MCS Remission (Alternative Definition) at Week 8 [ Time Frame: Week 8 ]
The MCS remission (alternative definition) was defined as a 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 stools more than normal), and PGA subscore (range: 0 to 3 with higher score indicating the severe disease) of 0, and an endoscopic subscore (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]) of 0 or 1 for an overall MCS of ≤ 1. Total score for MCS ranged from 0 to 12 (sum of all subscores), with higher scores indicating disease worsening.
Inclution Criteria
Inclusion Criteria:
Subjects will be eligible if they meet all of the following inclusion criteria:
1) Must have the ability to understand and sign a written informed
consent form, which must be obtained prior to initiation of study
procedures
2) Males or non-pregnant, non-lactating females, ages 18 to 75 years,
inclusive based on the date of the screening visit
3) Documented diagnosis of UC of at least 6 months AND with a
minimum disease extent of 15 cm from the anal verge
4) A surveillance colonoscopy is required at screening in subjects with
a history of ulcerative colitis for 8 or more years, if one was not
performed in the prior 24 months
5) Moderately to severely active UC as determined by a centrally read
endoscopy score ≥ 2, a rectal bleeding score ≥ 1, a stool frequency
score ≥ 1 and PGA of 2 or 3 as determined by the Mayo clinical
scoring system with endoscopy occurring within 14 days to first
dose of study drug
6) Demonstrated at any time over the prior 5 years, an inadequate
clinical response or loss of response to, or intolerance of at least one
of the following agents:
Corticosteroids
Active disease despite a history of at least one 4-week induction
regimen of a dose equivalent to prednisone 30 mg daily for
2 weeks or IV for 1 week, OR
Two failed attempts to taper steroids below a dose equivalent of
10 mg daily prednisone, OR
History of steroid intolerance including, but not limited to,
Cushing’s syndrome, osteopenia/osteoporosis, hyperglycemia,
insomnia, serious infections, depression, allergic reactions,
mood disturbances, or any other condition that contributed to
discontinuation of the agent
Immunomodulators
Active disease despite a history of at least a 12 week regimen of
oral azathioprine (≥ 1.5 mg/kg) or 6-mercaptopurine (6-MP)
(≥ 0.75 mg/kg), OR
History of intolerance to at least one immunomodulator
including, but not limited to, serious infections, hepatotoxicity,
cytopenia, pancreatitis, TPMT genetic mutation, allergic
reactions, or any other condition that contributed to
discontinuation of the agent
TNFα Antagonists
Active disease despite a history of at least one 4-8 week
induction regimen of infliximab, adalimumab, certolizumab,
golimumab, or biosimilar OR
Recurrence of symptoms during maintenance therapy with the
above agents, OR
History of intolerance to any TNFα agents including, but not
limited to, serious infections, hepatotoxicity, heart failure,
allergic reactions, or any other condition that contributed to
discontinuation of the agent
Vedolizumab
Active disease despite a history of at least a 14 week induction
regimen, OR
Recurrence of symptoms during maintenance therapy with the
above agents, OR
History of intolerance to vedolizumab including, but not limited
to, serious infections, hepatotoxicity, cytopenia, allergic
reactions, or any other condition that contributed to
discontinuation of the agent
7) May be receiving the following drugs:
Oral 5-ASA compounds provided the dose has been stable for at
least 2 weeks prior to screening, and/or
Oral corticosteroid therapy (prednisone at a stable dose of
≤ 30 mg/day or equivalent) provided the dose has been stable for
2 weeks prior to screening, and/or
Azathioprine or 6-MP provided the dose has been stable for 8 weeks
prior to screening
8) Females of childbearing potential (see definition in Appendix 7)
must have a negative pregnancy test at screening and baseline.
9) Male subjects and female subjects of childbearing potential who
engage in heterosexual intercourse must agree to use protocol
specified method(s) of contraception as described in Appendix 7.
Subjects will be eligible if they meet all of the following inclusion criteria:
1) Must have the ability to understand and sign a written informed
consent form, which must be obtained prior to initiation of study
procedures
2) Males or non-pregnant, non-lactating females, ages 18 to 75 years,
inclusive based on the date of the screening visit
3) Documented diagnosis of UC of at least 6 months AND with a
minimum disease extent of 15 cm from the anal verge
4) A surveillance colonoscopy is required at screening in subjects with
a history of ulcerative colitis for 8 or more years, if one was not
performed in the prior 24 months
5) Moderately to severely active UC as determined by a centrally read
endoscopy score ≥ 2, a rectal bleeding score ≥ 1, a stool frequency
score ≥ 1 and PGA of 2 or 3 as determined by the Mayo clinical
scoring system with endoscopy occurring within 14 days to first
dose of study drug
6) Demonstrated at any time over the prior 5 years, an inadequate
clinical response or loss of response to, or intolerance of at least one
of the following agents:
Corticosteroids
Active disease despite a history of at least one 4-week induction
regimen of a dose equivalent to prednisone 30 mg daily for
2 weeks or IV for 1 week, OR
Two failed attempts to taper steroids below a dose equivalent of
10 mg daily prednisone, OR
History of steroid intolerance including, but not limited to,
Cushing’s syndrome, osteopenia/osteoporosis, hyperglycemia,
insomnia, serious infections, depression, allergic reactions,
mood disturbances, or any other condition that contributed to
discontinuation of the agent
Immunomodulators
Active disease despite a history of at least a 12 week regimen of
oral azathioprine (≥ 1.5 mg/kg) or 6-mercaptopurine (6-MP)
(≥ 0.75 mg/kg), OR
History of intolerance to at least one immunomodulator
including, but not limited to, serious infections, hepatotoxicity,
cytopenia, pancreatitis, TPMT genetic mutation, allergic
reactions, or any other condition that contributed to
discontinuation of the agent
TNFα Antagonists
Active disease despite a history of at least one 4-8 week
induction regimen of infliximab, adalimumab, certolizumab,
golimumab, or biosimilar OR
Recurrence of symptoms during maintenance therapy with the
above agents, OR
History of intolerance to any TNFα agents including, but not
limited to, serious infections, hepatotoxicity, heart failure,
allergic reactions, or any other condition that contributed to
discontinuation of the agent
Vedolizumab
Active disease despite a history of at least a 14 week induction
regimen, OR
Recurrence of symptoms during maintenance therapy with the
above agents, OR
History of intolerance to vedolizumab including, but not limited
to, serious infections, hepatotoxicity, cytopenia, allergic
reactions, or any other condition that contributed to
discontinuation of the agent
7) May be receiving the following drugs:
Oral 5-ASA compounds provided the dose has been stable for at
least 2 weeks prior to screening, and/or
Oral corticosteroid therapy (prednisone at a stable dose of
≤ 30 mg/day or equivalent) provided the dose has been stable for
2 weeks prior to screening, and/or
Azathioprine or 6-MP provided the dose has been stable for 8 weeks
prior to screening
8) Females of childbearing potential (see definition in Appendix 7)
must have a negative pregnancy test at screening and baseline.
9) Male subjects and female subjects of childbearing potential who
engage in heterosexual intercourse must agree to use protocol
specified method(s) of contraception as described in Appendix 7.
Exclusion Criteria
Exclusion Criteria:
Subjects will be ineligible if they meet any of the following exclusion
criteria:
1) Known hypersensitivity to the study investigational medicinal
products
2) Exhibit severe UC as defined by the following criteria:
≥ 6 bloody stools daily AND one or more of the following:
Oral temperature > 100.3 °F ( or 38 °C)
Pulse > 90 beats/minute
3) Laboratory parameters:
Liver panel (AST, ALT, total bilirubin, alkaline phosphatase)
> 3 times the ULN
Serum creatinine > 2 times the ULN
Hemoglobin < 8 g/dL (both males and females)
Absolute neutrophil count (ANC) < 1.5 × 109
/L (1,500 mm3
)
Platelets < 100 × 109
/L
4) Use of rectal formulations of 5-ASA compounds or corticosteroids
2 weeks prior to screening
5) Crohn’s disease or indeterminate colitis
6) History of colectomy, partial colectomy, or dysplasia on biopsy
7) History of colonic or small bowel stoma
8) Stool sample positive for clostridium difficile (C. difficile) toxin,
Escherichia coli, Salmonella, Shigella, Campylobacter or Yersinia
9) Stool sample positive for ova and parasites test (O&P) unless
approved by the medical monitor
10) Treatment with infliximab, adalimumab, natalizumab, golimumab,
vedolizumab, certolizumab, or TNFα biosimilar agent 4 weeks prior
to screening (and last dose must be at least 8 weeks prior to
randomization)
11) Treatment with non-biologic therapies (eg, cyclosporine,
thalidomide) other than those permitted in Section 5.4 at least
4 weeks prior to screening
12) Other clinically significant active infection
13) Chronic medical or psychiatric problem that may interfere with
subject’s ability to comply with study procedures
14) Co-infection with chronic HIV, hepatitis B or hepatitis C
15) Active tuberculosis or history of latent tuberculosis that has not been
treated
16) History of malignancy in the last 5 years except for subjects who
have been successfully treated for non-melanoma skin cancer or
cervical carcinoma in situ
17) Any other investigational medicinal therapy or investigational
biologics use 4 weeks prior to screening (and at least 8 weeks prior
to randomization)
18) Any chronic medical condition (including, but not limited to, cardiac
or pulmonary disease, alcohol or drug abuse) that, in the opinion of
the Investigator, would make the subject unsuitable for the study or
would prevent compliance with the study protocol procedures
19) Females who may wish to become pregnant and/or plan to undergo
egg donation or egg harvesting for the purpose of current or future
fertilization during the course of the study and up to 30 days of the
last dose of the study drug
20) Male subjects unwilling to refrain from sperm donation for at least
90 days after the last dose of study drug
Subjects will be ineligible if they meet any of the following exclusion
criteria:
1) Known hypersensitivity to the study investigational medicinal
products
2) Exhibit severe UC as defined by the following criteria:
≥ 6 bloody stools daily AND one or more of the following:
Oral temperature > 100.3 °F ( or 38 °C)
Pulse > 90 beats/minute
3) Laboratory parameters:
Liver panel (AST, ALT, total bilirubin, alkaline phosphatase)
> 3 times the ULN
Serum creatinine > 2 times the ULN
Hemoglobin < 8 g/dL (both males and females)
Absolute neutrophil count (ANC) < 1.5 × 109
/L (1,500 mm3
)
Platelets < 100 × 109
/L
4) Use of rectal formulations of 5-ASA compounds or corticosteroids
2 weeks prior to screening
5) Crohn’s disease or indeterminate colitis
6) History of colectomy, partial colectomy, or dysplasia on biopsy
7) History of colonic or small bowel stoma
8) Stool sample positive for clostridium difficile (C. difficile) toxin,
Escherichia coli, Salmonella, Shigella, Campylobacter or Yersinia
9) Stool sample positive for ova and parasites test (O&P) unless
approved by the medical monitor
10) Treatment with infliximab, adalimumab, natalizumab, golimumab,
vedolizumab, certolizumab, or TNFα biosimilar agent 4 weeks prior
to screening (and last dose must be at least 8 weeks prior to
randomization)
11) Treatment with non-biologic therapies (eg, cyclosporine,
thalidomide) other than those permitted in Section 5.4 at least
4 weeks prior to screening
12) Other clinically significant active infection
13) Chronic medical or psychiatric problem that may interfere with
subject’s ability to comply with study procedures
14) Co-infection with chronic HIV, hepatitis B or hepatitis C
15) Active tuberculosis or history of latent tuberculosis that has not been
treated
16) History of malignancy in the last 5 years except for subjects who
have been successfully treated for non-melanoma skin cancer or
cervical carcinoma in situ
17) Any other investigational medicinal therapy or investigational
biologics use 4 weeks prior to screening (and at least 8 weeks prior
to randomization)
18) Any chronic medical condition (including, but not limited to, cardiac
or pulmonary disease, alcohol or drug abuse) that, in the opinion of
the Investigator, would make the subject unsuitable for the study or
would prevent compliance with the study protocol procedures
19) Females who may wish to become pregnant and/or plan to undergo
egg donation or egg harvesting for the purpose of current or future
fertilization during the course of the study and up to 30 days of the
last dose of the study drug
20) Male subjects unwilling to refrain from sperm donation for at least
90 days after the last dose of study drug
The Estimated Number of Participants
-
Taiwan
25 participants
-
Global
1600 participants
