Clinical Trials List
Protocol NumberGS-US-373-1499
NCT Number(ClinicalTrials.gov Identfier)NCT02862574
2016-12-15 - 2019-12-31
Phase II
Terminated6
ICD-10M06
Other rheumatoid arthritis
ICD-10M06.9
Rheumatoid arthritis, unspecified
ICD-9714.0
Rheumatoid arthritis
Evaluation of the Efficacy and Safety of GS-5745 as Add-On Therapy to a Tumor Necrosis Factor Inhibitor and Methotrexate Regimen in Subjects with Moderate to Severe Rheumatoid Arthritis
-
Trial Applicant
GILEAD SCIENCES HONG KONG LIMITED
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Sponsor
Gilead Sciences HK Ltd. Taiwan Branch
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 劉峰誠 無
- Tsung-Yun Hou 無
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 洪偉哲 無
- 蔡嘉哲 無
- 黃建中 無
- Po-Hao Huang 無
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Principal Investigator
Co-Principal Investigator
- Joung-Liang Lan 未分科
Audit
None
Linkou Chang Gung Medical Foundation
Taiwan National PI
方耀凡
Co-Principal Investigator
- Chang-Fu Kuo 無
- 張哲慈 無
- Ping-Han Tsai 無
- Shue-Fen Lo 無
- 陳彥輔 無
- TianMing Zhan 無
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
類風濕性關節炎
Objectives
The primary objective of this study is as follows:
To assess the efficacy of GS-5745 versus placebo as an add-on therapy to a TNF inhibitor and
methotrexate in subjects with moderately to severely active rheumatoid arthritis (RA)
The secondary objectives of this study are as follows:
To assess the safety and tolerability of GS-5745 versus placebo as an add-on therapy with a
TNF inhibitor and methotrexate in subjects with moderately to severely active RA
To assess the pharmacokinetics (PK) of GS-5745 as an add-on therapy with a TNF inhibitor
and methotrexate in subjects with moderately to severely active RA
The exploratory objectives of this study are as follows:
To explore biomarkers of clinical benefit, mechanism of action and impact of GS-5745
therapy in subjects with moderately to severely active RA
Test Drug
GS-5745
Active Ingredient
GS-5745
Dosage Form
Solution for injection in pre-filled syringe
Dosage
150 mg
Endpoints
The primary endpoint of this study includes:
Change in DAS28(CRP) from Baseline to Week 12
The secondary endpoints of this study include:
Proportion of subjects that achieve DAS28(CRP) < 3.2 at Week 12
Proportion of subjects that achieve DAS28(CRP) < 2.6 at Week 12
Assess plasma concentrations of GS-5745
Change in DAS28(CRP) from Baseline to Week 12
The secondary endpoints of this study include:
Proportion of subjects that achieve DAS28(CRP) < 3.2 at Week 12
Proportion of subjects that achieve DAS28(CRP) < 2.6 at Week 12
Assess plasma concentrations of GS-5745
Inclution Criteria
1) Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of the study procedures; subjects who need a representative/guardian to provide consent are not permitted in this study
2) Male or female subjects between 18 (20 in Taiwan) and 80 years of age inclusive, at time of signing initial informed consent
3) Diagnosis of RA according to the 2010 ACR/EULAR classification criteria, confirmed at Screening
4) You must meet Class I, II, or III of the ACR 1991 Revised Criteria for Global Functional Status in RA at Screening
5) Must have taken oral or parenteral methotrexate (MTX) dosed from 7.5 to 25 mg/week continuously for at least 12 weeks and tolerated this medication, with at least 6 weeks of stable dose (defined as no change in prescription) prior to the first dose of study drug
•Subjects on MTX may also be on concurrent chloroquine or hydroxychloroquine at a stable dose (defined as no change in prescription) for at least 4 weeks prior to Baseline: if so, they should plan to continue this medication for the duration of the study
•Must be receiving folic or folinic acid supplementation at Day 1 and throughout the duration of the study, dosed as per investigator
6) Must have ≥ 12 weeks of ongoing treatment with an approved, SC formulation of TNF inhibitor (adalimumab, certolizumab, etanercept, or golimumab, or marketed biosimilar TNF inhibitor), with at least 6 weeks of stable dose (defined as no change in prescription) defined as:
•Must have a DAS28(CRP)>3.2 at Screening
AND
•Must have ≥ 3 swollen joints and ≥ 3 tender joints among 28 joints assessed (using DAS28) at Screening and at Baseline (need not be the same joints)
7) You have previously received other biologic DMARDs for the treatment of RA are eligible, providing the following washout periods for these have been met:
•Rituximab – none for at least 6 months prior to Baseline and you have a CD19+ B cell count in normal range (per central lab) at Screening
•Infliximab – none for at least 8 weeks prior to Baseline
•Tocilizumab – none for at least 8 weeks prior to Baseline
8) Non-steroidal anti-inflammatory drugs (NSAIDs) and/or oral corticosteroids (≤ 10 mg prednisone/day or equivalent) at a stable dose (defined as no change in prescription) for ≥ 4 weeks prior to Baseline are allowed and should be continued at the same stable dose throughout the blinded period of the study; PRN NSAIDs for indications other than RA are also allowed.
9) TB Screening: Subjects must meet either a. or b.:
a. A negative history of TB infection and a negative QuantiFERON® TB-Gold In-Tube test and chest x ray results (see below). QuantiFERON® tests with inconclusive results may be repeated one time. If the repeat result is also is inconclusive, the subject will be excluded from the study.
OR,
b. Subjects with a history of latent TB treated with a full course of prophylaxis as per local guidelines, are allowed per investigator judgment. It is the responsibility of the investigator to verify the adequacy of previous treatment and to provide appropriate documentation. In these cases, no QuantiFERON® test need be obtained. In addition, must be approved by the medical monitor prior to enrollment. (Any new diagnosis of latent TB or prior untreated/ partially treated latent TB is NOT allowed [ie, subjects who require prophylactic therapy for TB during the study]. Any prior history of active TB [regardless of treatment] is exclusionary.
10) A negative chest x-ray (views per local guidelines) for active TB or other lung disease at Screening; or a chest x-ray within 90 days of Screening if films or report are available for investigator review
11) A negative pregnancy test is required for female subjects of childbearing potential (as defined per protocol), at Screening and at Day 1, prior to dosing of study drug Female subjects must not to become pregnant for 30 days after the last dose of GS-5745
12) If you are of child-bearing potential (as defined in protocol), you must agree to use protocol specified contraceptive measures throughout the study and for 30 days after the last dose of study drug. Female subjects must agree not to become pregnant for 30 days after the last dose of study drug. Male and female subjects taking methotrexate or other drugs should also follow contraception guidelines in the relevant product local label
13) Lactating females must agree to discontinue breastfeeding prioir to dosing of study drug and for the duration of the study.
2) Male or female subjects between 18 (20 in Taiwan) and 80 years of age inclusive, at time of signing initial informed consent
3) Diagnosis of RA according to the 2010 ACR/EULAR classification criteria, confirmed at Screening
4) You must meet Class I, II, or III of the ACR 1991 Revised Criteria for Global Functional Status in RA at Screening
5) Must have taken oral or parenteral methotrexate (MTX) dosed from 7.5 to 25 mg/week continuously for at least 12 weeks and tolerated this medication, with at least 6 weeks of stable dose (defined as no change in prescription) prior to the first dose of study drug
•Subjects on MTX may also be on concurrent chloroquine or hydroxychloroquine at a stable dose (defined as no change in prescription) for at least 4 weeks prior to Baseline: if so, they should plan to continue this medication for the duration of the study
•Must be receiving folic or folinic acid supplementation at Day 1 and throughout the duration of the study, dosed as per investigator
6) Must have ≥ 12 weeks of ongoing treatment with an approved, SC formulation of TNF inhibitor (adalimumab, certolizumab, etanercept, or golimumab, or marketed biosimilar TNF inhibitor), with at least 6 weeks of stable dose (defined as no change in prescription) defined as:
•Must have a DAS28(CRP)>3.2 at Screening
AND
•Must have ≥ 3 swollen joints and ≥ 3 tender joints among 28 joints assessed (using DAS28) at Screening and at Baseline (need not be the same joints)
7) You have previously received other biologic DMARDs for the treatment of RA are eligible, providing the following washout periods for these have been met:
•Rituximab – none for at least 6 months prior to Baseline and you have a CD19+ B cell count in normal range (per central lab) at Screening
•Infliximab – none for at least 8 weeks prior to Baseline
•Tocilizumab – none for at least 8 weeks prior to Baseline
8) Non-steroidal anti-inflammatory drugs (NSAIDs) and/or oral corticosteroids (≤ 10 mg prednisone/day or equivalent) at a stable dose (defined as no change in prescription) for ≥ 4 weeks prior to Baseline are allowed and should be continued at the same stable dose throughout the blinded period of the study; PRN NSAIDs for indications other than RA are also allowed.
9) TB Screening: Subjects must meet either a. or b.:
a. A negative history of TB infection and a negative QuantiFERON® TB-Gold In-Tube test and chest x ray results (see below). QuantiFERON® tests with inconclusive results may be repeated one time. If the repeat result is also is inconclusive, the subject will be excluded from the study.
OR,
b. Subjects with a history of latent TB treated with a full course of prophylaxis as per local guidelines, are allowed per investigator judgment. It is the responsibility of the investigator to verify the adequacy of previous treatment and to provide appropriate documentation. In these cases, no QuantiFERON® test need be obtained. In addition, must be approved by the medical monitor prior to enrollment. (Any new diagnosis of latent TB or prior untreated/ partially treated latent TB is NOT allowed [ie, subjects who require prophylactic therapy for TB during the study]. Any prior history of active TB [regardless of treatment] is exclusionary.
10) A negative chest x-ray (views per local guidelines) for active TB or other lung disease at Screening; or a chest x-ray within 90 days of Screening if films or report are available for investigator review
11) A negative pregnancy test is required for female subjects of childbearing potential (as defined per protocol), at Screening and at Day 1, prior to dosing of study drug Female subjects must not to become pregnant for 30 days after the last dose of GS-5745
12) If you are of child-bearing potential (as defined in protocol), you must agree to use protocol specified contraceptive measures throughout the study and for 30 days after the last dose of study drug. Female subjects must agree not to become pregnant for 30 days after the last dose of study drug. Male and female subjects taking methotrexate or other drugs should also follow contraception guidelines in the relevant product local label
13) Lactating females must agree to discontinue breastfeeding prioir to dosing of study drug and for the duration of the study.
Exclusion Criteria
1) Current treatment with any disease modifying anti-rheumatic drug (DMARD) other than MTX, chloroquine or hydroxychloroquine), or other immune modulating/suppressive non-biologic and biologic medications
2) Intra-articular corticosteroid injection within 4 weeks of Baseline
3) Any infection requiring oral antimicrobial therapy within 2 weeks prior to Baseline.
4) Previous treatment with GS-5745; known hypersensitivity to GS-5745 or its formulation excipients.
5) Known hypersensitivity to the TNF inhibitor or its formulation excipients that the subject is receiving at Screening
6) Any live or attenuated vaccines within 4 weeks prior to the first dose of study drug or plan to be vaccinated with these vaccines at any time during the study or within 12 weeks after the last dose of study drug.
7) Current inflammatory joint disease, other than RA, such as gout, reactive arthritis, psoriatic arthritis, seronegative spondylarthritis, or Lyme disease, OR other current autoimmune diseases such as: systemic lupus erythematosus (SLE), inflammatory bowel disease, fibromyalgia, polymyalgia rheumatica, scleroderma, inflammatory myopathy, mixed connective tissue disease, or other overlap syndrome that would interfere with the evaluation of RA or require protocol prohibited medication (subjects with Sjogren’s syndrome or controlled thyroiditis as defined by the investigator are not excluded)
8) Active systemic involvement secondary to RA such as vasculitis or Felty’s syndrome
9) History of any of the following within 12 months of Baseline:
a) infection requiring parenteral antibiotics or hospitalization,
b) any life-threatening infection,
c) sepsis
10) History of infected prosthetic joint at any time, with the prosthesis still in situ
11) Significant blood loss (>450 mL) or transfusion of blood product within 12 weeks prior to Day 1.
12) Tests performed at the central laboratory at Screening that meet any of the criteria below (out of range lab values may be rechecked one time, after consultation with the sponsor or its designee, before subject is considered a screen-failure):
a) Hemoglobin <8.0 g/dL (International System of Units [SI]: <80 g/L);
b) White blood cells <3.0 x 103 cells/mm3 (SI: <3.0 x 109 cells/L);
c) Neutrophils <1.5 x 103 cells/mm3 (SI: <1.5 x 109 cells/L);
d) Lymphocytes <0.5 x 103 cells/mm3 (SI: <0.5 x 109 cells/L);
e) Platelets <100 x 103 cells/mm3 (SI: <100 x 109 cells/L);
f) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2.0x ULN;
g) Total bilirubin level ≥2x ULN unless the subject has been diagnosed with Gilbert’s disease and this is clearly documented;
h) Estimated glomerular filtration rate <40 mL/min/1.73m2 based on the Modification of Diet in Renal Disease (MDRD) formula.
i) Positive HIV serology during screening
j) Evidence of active Hepatitis B Virus (HBV) infection. Subject with positive HBV surface antigen (HBsAg) at screening are excluded from the study. Subjects with negative HBsAg who have positive HBV core Ab, require reflex testing for HBV DNA. Subjects with positive HBV DNA at screening will be excluded. Subjects with positive HBV core Ab, and negative HBV DNA are eligible for study entry, per investigator judgment, but may require prophylactic treatment in accordance with HBV treatment guidelines/local standard of care, and require ongoing monitoring with blood tests for HBV DNA every 3 months, as outlined in the schedule of assessments. Subjects with evidence of active Hepatitis B during the study, as evidenced by DNA positivity, will be discontinued from the study drug as outlined in the protocol.
k) Evidence of active Hepatitis C Virus (HCV) infection. Subjects with a positive HCV Ab at Screening require reflex testing for HCV RNA. Subjects with a positive Hep C RNA at Screening will be excluded. Subjects with a positive HCV Ab, but a negative HCV RNA are eligible, per investigator judgment, but require ongoing HCV RNA monitoring every 3 months. Subjects with evidence of active Hepatitis C during the study, as evidenced by RNA positivity, will be discontinued from the study drug as outlined in the protocol.
13) Any uncontrolled clinically significant laboratory abnormality that would affect interpretation of study data or the subject’s participation in the study, per judgement of investigator.
14) Current malignancy, or a history of malignancy or lymphoproliferative disorder within 10 years of Screening, except:
a) Carcinoma in situ of the cervix that has been successfully treated
b) Basal or squamous cell cancer or other localized non-melanoma skin cancer that has been successfully treated
15) Participation in another investigational drug study within 1 month of Screening (for a small molecule) or within 3 months or 5 drug half-lives prior to Screening, whichever is longer (for a biologic agent)
16) Male subjects who are unwilling to refrain from sperm donation during the study and for 90 days after their last dose of study drug
17) Female subjects who are unwilling to refrain from egg donation or egg harvesting (for the purpose of current or future fertilization) during the course of the study and up to 30 days after their last dose of the study drug
18) Presence of any condition that could, in the opinion of the investigator, compromise the subject’s ability to participate in the study, eg, substance abuse, alcoholism, or an unstable psychiatric condition.
19) Known hypersensitivity to rubber or latex
20) Have undergone surgical treatments for RA including synovectomy or arthroplasty within the last 12 weeks prior to Screening or planned such surgery during the study
21) History of or current moderate to severe congestive heart failure (New York Heart Association [NYHA] class III or IV), or within the last 6 months, a cerebrovascular accident, myocardial infarction, unstable angina, unstable arrhythmia, or a new or significant ECG finding at Screening, or any other cardiovascular condition which, in the opinion of the investigator, would put the subject at risk by participating in the study.
22) Any chronic, uncontrolled medical condition which would put the subject at increased risk during the study, such as uncontrolled: diabetes, hypertension, morbid obesity, thyroid, adrenal, pulmonary, hepatic, renal, neurologic or psychiatric disease, or other disease of concern, as per judgment of the investigator
2) Intra-articular corticosteroid injection within 4 weeks of Baseline
3) Any infection requiring oral antimicrobial therapy within 2 weeks prior to Baseline.
4) Previous treatment with GS-5745; known hypersensitivity to GS-5745 or its formulation excipients.
5) Known hypersensitivity to the TNF inhibitor or its formulation excipients that the subject is receiving at Screening
6) Any live or attenuated vaccines within 4 weeks prior to the first dose of study drug or plan to be vaccinated with these vaccines at any time during the study or within 12 weeks after the last dose of study drug.
7) Current inflammatory joint disease, other than RA, such as gout, reactive arthritis, psoriatic arthritis, seronegative spondylarthritis, or Lyme disease, OR other current autoimmune diseases such as: systemic lupus erythematosus (SLE), inflammatory bowel disease, fibromyalgia, polymyalgia rheumatica, scleroderma, inflammatory myopathy, mixed connective tissue disease, or other overlap syndrome that would interfere with the evaluation of RA or require protocol prohibited medication (subjects with Sjogren’s syndrome or controlled thyroiditis as defined by the investigator are not excluded)
8) Active systemic involvement secondary to RA such as vasculitis or Felty’s syndrome
9) History of any of the following within 12 months of Baseline:
a) infection requiring parenteral antibiotics or hospitalization,
b) any life-threatening infection,
c) sepsis
10) History of infected prosthetic joint at any time, with the prosthesis still in situ
11) Significant blood loss (>450 mL) or transfusion of blood product within 12 weeks prior to Day 1.
12) Tests performed at the central laboratory at Screening that meet any of the criteria below (out of range lab values may be rechecked one time, after consultation with the sponsor or its designee, before subject is considered a screen-failure):
a) Hemoglobin <8.0 g/dL (International System of Units [SI]: <80 g/L);
b) White blood cells <3.0 x 103 cells/mm3 (SI: <3.0 x 109 cells/L);
c) Neutrophils <1.5 x 103 cells/mm3 (SI: <1.5 x 109 cells/L);
d) Lymphocytes <0.5 x 103 cells/mm3 (SI: <0.5 x 109 cells/L);
e) Platelets <100 x 103 cells/mm3 (SI: <100 x 109 cells/L);
f) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2.0x ULN;
g) Total bilirubin level ≥2x ULN unless the subject has been diagnosed with Gilbert’s disease and this is clearly documented;
h) Estimated glomerular filtration rate <40 mL/min/1.73m2 based on the Modification of Diet in Renal Disease (MDRD) formula.
i) Positive HIV serology during screening
j) Evidence of active Hepatitis B Virus (HBV) infection. Subject with positive HBV surface antigen (HBsAg) at screening are excluded from the study. Subjects with negative HBsAg who have positive HBV core Ab, require reflex testing for HBV DNA. Subjects with positive HBV DNA at screening will be excluded. Subjects with positive HBV core Ab, and negative HBV DNA are eligible for study entry, per investigator judgment, but may require prophylactic treatment in accordance with HBV treatment guidelines/local standard of care, and require ongoing monitoring with blood tests for HBV DNA every 3 months, as outlined in the schedule of assessments. Subjects with evidence of active Hepatitis B during the study, as evidenced by DNA positivity, will be discontinued from the study drug as outlined in the protocol.
k) Evidence of active Hepatitis C Virus (HCV) infection. Subjects with a positive HCV Ab at Screening require reflex testing for HCV RNA. Subjects with a positive Hep C RNA at Screening will be excluded. Subjects with a positive HCV Ab, but a negative HCV RNA are eligible, per investigator judgment, but require ongoing HCV RNA monitoring every 3 months. Subjects with evidence of active Hepatitis C during the study, as evidenced by RNA positivity, will be discontinued from the study drug as outlined in the protocol.
13) Any uncontrolled clinically significant laboratory abnormality that would affect interpretation of study data or the subject’s participation in the study, per judgement of investigator.
14) Current malignancy, or a history of malignancy or lymphoproliferative disorder within 10 years of Screening, except:
a) Carcinoma in situ of the cervix that has been successfully treated
b) Basal or squamous cell cancer or other localized non-melanoma skin cancer that has been successfully treated
15) Participation in another investigational drug study within 1 month of Screening (for a small molecule) or within 3 months or 5 drug half-lives prior to Screening, whichever is longer (for a biologic agent)
16) Male subjects who are unwilling to refrain from sperm donation during the study and for 90 days after their last dose of study drug
17) Female subjects who are unwilling to refrain from egg donation or egg harvesting (for the purpose of current or future fertilization) during the course of the study and up to 30 days after their last dose of the study drug
18) Presence of any condition that could, in the opinion of the investigator, compromise the subject’s ability to participate in the study, eg, substance abuse, alcoholism, or an unstable psychiatric condition.
19) Known hypersensitivity to rubber or latex
20) Have undergone surgical treatments for RA including synovectomy or arthroplasty within the last 12 weeks prior to Screening or planned such surgery during the study
21) History of or current moderate to severe congestive heart failure (New York Heart Association [NYHA] class III or IV), or within the last 6 months, a cerebrovascular accident, myocardial infarction, unstable angina, unstable arrhythmia, or a new or significant ECG finding at Screening, or any other cardiovascular condition which, in the opinion of the investigator, would put the subject at risk by participating in the study.
22) Any chronic, uncontrolled medical condition which would put the subject at increased risk during the study, such as uncontrolled: diabetes, hypertension, morbid obesity, thyroid, adrenal, pulmonary, hepatic, renal, neurologic or psychiatric disease, or other disease of concern, as per judgment of the investigator
The Estimated Number of Participants
-
Taiwan
12 participants
-
Global
75 participants
