Clinical Trials List
Protocol NumberCB8025-41837
Active
2025-12-01 - 2032-08-02
Others
Not yet recruiting7
ICD-10K83.0
Cholangitis
ICD-9576.1
Cholangitis
AFFIRM: A randomized, double-blind, placebo-controlled trial designed to evaluate the effect of Seladelpar on clinical outcomes in patients with primary biliary cholangitis (PBC) and compensated cirrhosis.
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Trial Applicant
GILEAD SCIENCES HONG KONG LIMITED
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Sponsor
Hong Kong-based Gilia Pharmaceutical Co., Ltd. Taiwan Branch
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Trial scale
Multi-Regional Multi-Center
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Update
2026/07/01
Investigators and Locations
Co-Principal Investigator
- PEI-JER CHEN 無
- Chun-Jen Liu 無
- Jia-Horng Kao 無
- Chen-Hua Liu 無
- 吳志宏 無
- Shih-Jer Hsu 無
- 曾岱宗 無
- 楊宏志 無
- 鄭永銘 無
- 洪俊銘 無
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Wan-Long Chuang 無
- Jee-Fu Huang 無
- Chung-Feng Huang 無
- Ming-Lun Yeh 無
- 梁博程 無
- Chia-Yen Dai 無
- 魏鈺儒 無
- 王志文 無
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- 邱彥程 無
- Chiu Hung Chiu 無
- 簡世杰 無
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Principal Investigator
Rong-Nan Chien
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Condition/Disease
1. EFS should be assessed by the time elapsed from the start of treatment to the first occurrence of any of the following adjudicated events at week 156: a. death from any cause b. liver transplantation c. MELD score ≥ 15 d. ascites requiring treatment e. hospitalization for any of the following criterion events: i. esophageal or gastric variceal bleeding ii. hepatic encephalopathy (defined as West Haven score ≥ 2) iii. spontaneous bacterial peritonitis confirmed by diagnostic paracentesis based on WBC count, differential, and/or positive growth in aerobic and/or anaerobic blood cultures. Further details regarding clinical events requiring adjudication should be provided. 2. Assessment of treatment-induced adverse events (TEAEs); biochemical and hematological laboratory evaluation.
Objectives
Primary Objective
Efficacy: To evaluate the effect of seladelpar compared to placebo on event-free survival (EFS). EFS is defined as the time elapsed from the start of treatment to the first occurrence of any of the following adjudicated events at week 156:
• Death from any cause
• Liver transplantation
• Model for End-Stage Liver Disease (MELD) score ≥15
• Ascites requiring treatment
• Hospitalization due to any of the following qualifying events:
o Esophageal or gastric variceal bleeding
o Hepatic encephalopathy (defined as West Haven score ≥2)
o Spontaneous bacterial peritonitis confirmed by diagnostic paracentesis based on white blood cell (WBC) count, differential, and/or positive growth in aerobic and/or anaerobic blood cultures
Safety: To evaluate the safety of seladelpar compared to placebo during the 156-week treatment period
Secondary Objective:
To evaluate the effect of seladelpar on the following:
• Overall survival
• Liver transplant-free survival (LTFS) is defined as the time elapsed from the start of treatment to the first occurrence of liver-related death or liver transplantation.
• Time elapsed before hospitalization due to any of the following qualifying events:
o Esophageal or gastric variceal bleeding
o Hepatic encephalopathy or
o Spontaneous bacterial peritonitis
• Time elapsed before any other qualifying PBC clinical event (MELD score ≥ 15 and ascites requiring treatment)
Exploratory Goals: To assess the impact of disease and seladelpar on individual qualifying PBC clinical events, liver biochemical markers of disease and liver injury, liver histology, liver stiffness, disease and/or worsening biomarkers, pharmacokinetics (PK), patient-reported quality of life indicators, PBC prognostic criteria, and pruritus.
Test Drug
Seladelpar
Active Ingredient
Seladelpar Lysine
Dosage Form
Capsules
Dosage
5 mg or 10 mg
Endpoints
1. Assess EFS by the time elapsed from the start of treatment to the first occurrence of any of the following adjudicated events at week 156:
a. Death from any cause
b. Liver transplantation
c. MELD score ≥ 15
d. Ascites requiring treatment
e. Hospitalization due to any of the following criterion events:
i. Esophageal or gastric variceal bleeding
ii. Hepatic encephalopathy (defined as West Haven score ≥ 2)
iii. Spontaneous bacterial peritonitis confirmed by diagnostic paracentesis based on WBC count, differential, and/or positive growth in aerobic and/or anaerobic blood cultures. More detailed information on clinical events requiring adjudication is available for assessment.
2. Assess treatment-induced adverse events (TEAEs); biochemical and hematological laboratory evaluation.
a. Death from any cause
b. Liver transplantation
c. MELD score ≥ 15
d. Ascites requiring treatment
e. Hospitalization due to any of the following criterion events:
i. Esophageal or gastric variceal bleeding
ii. Hepatic encephalopathy (defined as West Haven score ≥ 2)
iii. Spontaneous bacterial peritonitis confirmed by diagnostic paracentesis based on WBC count, differential, and/or positive growth in aerobic and/or anaerobic blood cultures. More detailed information on clinical events requiring adjudication is available for assessment.
2. Assess treatment-induced adverse events (TEAEs); biochemical and hematological laboratory evaluation.
Inclution Criteria
To be eligible to participate in this trial, participants must meet all of the following criteria:
1. Written informed consent (signed and dated) and any authorizations required by local law must be provided.
2. Participants must be at least 18 years old.
3. Participants must have a history of PBC diagnosed based on any two of the following criteria:
a. Elevated ALP > 1.0 × ULN for at least 6 months.
b. Documented liver tissue biopsy results consistent with PBC.
c. Positive AMA titer (immunofluorescence assay > 1:40, or enzyme-linked immunosorbent assay showing M2 positivity) or positive PBC-specific ANA.
AMA-negative subjects must have liver tissue sections consistent with PBC or highly specific ANA, cholestasis, and evidence excluding other liver diseases.
4. Evidence of cirrhosis, including any of the following:
a. Historical tissue section results consistent with cirrhosis caused by PBC
b. Liver stiffness > 15 kPa as measured by a FibroScan® (or similar instrument) liver fibrosis scan
c. Liver computed tomography (CT), magnetic resonance imaging (MRI), or liver ultrasound consistent with a diagnosis of cirrhosis
d. A clinical diagnosis based on concomitant low platelet count (< 140 × 10³/µL) and meeting one or more of the following criteria within 8 weeks prior to screening:
i. Persistently low serum albumin (< 3.3 g/dL)
ii. Persistent international normalized ratio (INR) > 1.3 (without anticoagulation therapy)
5. CP grade A or B, but not meeting the criteria for liver function decompensation (exclusion criterion #) 4) Exclusion criteria for laboratory parameters (exclusion criterion #7)
6. Sexually active and fertile women must use at least one barrier method of contraception and a second effective method of contraception during the trial period and for at least 90 days after the last dose. Male subjects who have sexual intercourse with fertile female partners must use a barrier method of contraception during the trial period and for at least 90 days after the last dose, and their female partners must use a second effective method of contraception.
7. Subjects must be able to follow the instructions for administration of the investigational drug and complete the SOA.
1. Written informed consent (signed and dated) and any authorizations required by local law must be provided.
2. Participants must be at least 18 years old.
3. Participants must have a history of PBC diagnosed based on any two of the following criteria:
a. Elevated ALP > 1.0 × ULN for at least 6 months.
b. Documented liver tissue biopsy results consistent with PBC.
c. Positive AMA titer (immunofluorescence assay > 1:40, or enzyme-linked immunosorbent assay showing M2 positivity) or positive PBC-specific ANA.
AMA-negative subjects must have liver tissue sections consistent with PBC or highly specific ANA, cholestasis, and evidence excluding other liver diseases.
4. Evidence of cirrhosis, including any of the following:
a. Historical tissue section results consistent with cirrhosis caused by PBC
b. Liver stiffness > 15 kPa as measured by a FibroScan® (or similar instrument) liver fibrosis scan
c. Liver computed tomography (CT), magnetic resonance imaging (MRI), or liver ultrasound consistent with a diagnosis of cirrhosis
d. A clinical diagnosis based on concomitant low platelet count (< 140 × 10³/µL) and meeting one or more of the following criteria within 8 weeks prior to screening:
i. Persistently low serum albumin (< 3.3 g/dL)
ii. Persistent international normalized ratio (INR) > 1.3 (without anticoagulation therapy)
5. CP grade A or B, but not meeting the criteria for liver function decompensation (exclusion criterion #) 4) Exclusion criteria for laboratory parameters (exclusion criterion #7)
6. Sexually active and fertile women must use at least one barrier method of contraception and a second effective method of contraception during the trial period and for at least 90 days after the last dose. Male subjects who have sexual intercourse with fertile female partners must use a barrier method of contraception during the trial period and for at least 90 days after the last dose, and their female partners must use a second effective method of contraception.
7. Subjects must be able to follow the instructions for administration of the investigational drug and complete the SOA.
Exclusion Criteria
To be eligible to participate in this trial, participants must not meet any of the following criteria:
1. Have received seladelpar for more than 26 weeks within the year prior to screening. The last dose of seladelpar must have been received at least 3 months prior to screening.
2. Have a medical condition other than PBC that the trial administrator believes may hinder full participation in the trial (e.g., cancer), jeopardize participant safety, or confound trial results (e.g., Parkinson's disease).
3. Have a history of liver transplantation, or be on the waiting list for posthumous organ donation or planned living organ donation. Subjects on the transplant list (e.g., according to regional guidelines) who are in a relatively early stage of disease may be eligible for transplantation if they do not meet other exclusion criteria.
4. Uncompensated cirrhosis, defined as a history of any of the following:
a. Ascites requiring treatment
b. History of esophageal or gastric varices with bleeding
c. Hepatic encephalopathy (defined as West Haven score ≥ 2) requiring hospitalization
d. Confirmation of spontaneous bacterial peritonitis by diagnostic paracentesis based on WBC count, differential, and/or aerobic and/or anaerobic blood cultures
e. Hepatorenal syndrome (type I or II)
f. Previous transjugular intrahepatic portosystemic shunt placement and/or previous portacaval shunt placement
g. Known hepatic venous pressure gradient (HVPG) > 12 mm Hg
5. Based on Doppler ultrasound or previous CT or MRI during the screening period. Results showed evidence of portal vein thrombosis.
6. Hospitalization for liver-related complications within 12 weeks prior to screening.
7. Laboratory parameters during screening:
a. ALP < 1.5 × ULN or ≥ 10 × ULN
b. ALT or AST ≥ 5 × ULN
c. TB ≥ 5 × ULN
d. Platelet count ≤ 50 × 10³/µL
e. Albumin ≤ 2.8 g/dL
f. Estimated glomerular filtration rate < 45 mL/min/1.73 m²
g. MELD score > 12. For subjects receiving anticoagulant therapy, the use of anticoagulants should be considered when measuring the baseline INR used to calculate the MELD score.
h. Serum AFP > 20 ng/mL
i. INR > 1.7
8. CP-C cirrhosis (i.e., CP score ≥ 10)
9. Concomitant liver disease, including but not limited to any of the following:
a. Evidence of acute viral hepatitis A
b. Hepatitis B virus infection (acute or chronic)
c. Hepatitis C virus (HCV) infection, defined as the presence of HCV d. Primary sclerosing cholangitis confirmed by cholangiography
e. Alcoholic liver disease
f. α1-antitrypsin deficiency
g. Non-alcoholic steatohepatitis confirmed by liver histology
h. Gilbert's syndrome with elevated total bilirubin or significant hemolysis
i. Hemochromatosis
j. Autoimmune hepatitis (AIH) diagnosed by the trial administrator based on immunoserological, liver biochemical, or previously confirmed liver histology results
k. Hepatobiliary malignancy diagnosed based on imaging, screening laboratory values, and/or clinical symptoms; exclusion of any patients with relevant medical history, current evidence, or high suspicion
10. Has undergone or plans to undergo Roux-en-Y gastric bypass surgery
11. Has been in 2 11. History of diagnosis or treatment of malignancy within the year, or ongoing malignancy evaluation; if appropriate treatment was received prior to screening, those who received local treatment for squamous or noninvasive basal cell carcinoma of the skin and cervical carcinoma in situ are permitted inclusion.
12. Known history of human immunodeficiency virus (HIV) infection, or a positive antibody test result during screening.
13. Clinically significant alcohol consumption, defined as >14 alcohol units per week (equivalent to 140 g) for women and >21 alcohol units per week (equivalent to 210 g) for men, or alcohol intake that cannot be reliably quantified.
14. Known or suspected clinically significant allergy to seladelpar or any of its components.
15. Started using UDCA within 6 months prior to screening or adjusted the UDCA dose within 12 weeks prior to screening. Subjects with a history of inadequate response or intolerance to UDCA, as assessed by the trial administrator, are also excluded. Subjects who cannot tolerate UDCA must have received their last dose > 12 weeks prior to screening.
16. Subjects who have received deoxyursolic acid or fibrates (such as bezafibrate, fenofibrate, elafibranor, lanifibranor, pemafibrate, or saroglitazar) within 6 weeks prior to screening.
17. Subjects who have received colchicine, methotrexate, azathioprine, or long-term systemic corticosteroids (> 2 weeks) within 8 weeks prior to screening. For non-hepatic, stable comorbidities, a maximum of prednisone 5 mg or equivalent once daily is permitted.
18. Any long-term treatment with other immunosuppressive therapies (e.g., cyclosporine, tacrolimus, anti-tumor necrosis factor [TNF], or other immunosuppressive biologics) within 6 months prior to screening.
19. Any dose adjustment of antipruritic medications (e.g., cholestyramine, naltrexone, rifampicin, sertraline) for treating pruritus within 1 month prior to screening.
20. Use of contraindicated or concomitant medications. Other medications that affect hepatic or gastrointestinal (GI) function (e.g., drug absorption) may be contraindicated, as determined by the trial administrator on an individual basis. The trial administrator should consult the trial sponsor's medical monitor as needed.
21. Treatment with any other experimental therapy or device within 30 days or 5 half-lives (whichever is longer) prior to screening.
22. Pregnancy and breastfeeding (applicable to women).
23. Having a severe specific infectious pneumonia (COVID-19) infection deemed clinically relevant by the trial administrator during the screening period.
24. Having undergone endoscopic treatment for esophageal or gastric varices within 6 months prior to screening.
1. Have received seladelpar for more than 26 weeks within the year prior to screening. The last dose of seladelpar must have been received at least 3 months prior to screening.
2. Have a medical condition other than PBC that the trial administrator believes may hinder full participation in the trial (e.g., cancer), jeopardize participant safety, or confound trial results (e.g., Parkinson's disease).
3. Have a history of liver transplantation, or be on the waiting list for posthumous organ donation or planned living organ donation. Subjects on the transplant list (e.g., according to regional guidelines) who are in a relatively early stage of disease may be eligible for transplantation if they do not meet other exclusion criteria.
4. Uncompensated cirrhosis, defined as a history of any of the following:
a. Ascites requiring treatment
b. History of esophageal or gastric varices with bleeding
c. Hepatic encephalopathy (defined as West Haven score ≥ 2) requiring hospitalization
d. Confirmation of spontaneous bacterial peritonitis by diagnostic paracentesis based on WBC count, differential, and/or aerobic and/or anaerobic blood cultures
e. Hepatorenal syndrome (type I or II)
f. Previous transjugular intrahepatic portosystemic shunt placement and/or previous portacaval shunt placement
g. Known hepatic venous pressure gradient (HVPG) > 12 mm Hg
5. Based on Doppler ultrasound or previous CT or MRI during the screening period. Results showed evidence of portal vein thrombosis.
6. Hospitalization for liver-related complications within 12 weeks prior to screening.
7. Laboratory parameters during screening:
a. ALP < 1.5 × ULN or ≥ 10 × ULN
b. ALT or AST ≥ 5 × ULN
c. TB ≥ 5 × ULN
d. Platelet count ≤ 50 × 10³/µL
e. Albumin ≤ 2.8 g/dL
f. Estimated glomerular filtration rate < 45 mL/min/1.73 m²
g. MELD score > 12. For subjects receiving anticoagulant therapy, the use of anticoagulants should be considered when measuring the baseline INR used to calculate the MELD score.
h. Serum AFP > 20 ng/mL
i. INR > 1.7
8. CP-C cirrhosis (i.e., CP score ≥ 10)
9. Concomitant liver disease, including but not limited to any of the following:
a. Evidence of acute viral hepatitis A
b. Hepatitis B virus infection (acute or chronic)
c. Hepatitis C virus (HCV) infection, defined as the presence of HCV d. Primary sclerosing cholangitis confirmed by cholangiography
e. Alcoholic liver disease
f. α1-antitrypsin deficiency
g. Non-alcoholic steatohepatitis confirmed by liver histology
h. Gilbert's syndrome with elevated total bilirubin or significant hemolysis
i. Hemochromatosis
j. Autoimmune hepatitis (AIH) diagnosed by the trial administrator based on immunoserological, liver biochemical, or previously confirmed liver histology results
k. Hepatobiliary malignancy diagnosed based on imaging, screening laboratory values, and/or clinical symptoms; exclusion of any patients with relevant medical history, current evidence, or high suspicion
10. Has undergone or plans to undergo Roux-en-Y gastric bypass surgery
11. Has been in 2 11. History of diagnosis or treatment of malignancy within the year, or ongoing malignancy evaluation; if appropriate treatment was received prior to screening, those who received local treatment for squamous or noninvasive basal cell carcinoma of the skin and cervical carcinoma in situ are permitted inclusion.
12. Known history of human immunodeficiency virus (HIV) infection, or a positive antibody test result during screening.
13. Clinically significant alcohol consumption, defined as >14 alcohol units per week (equivalent to 140 g) for women and >21 alcohol units per week (equivalent to 210 g) for men, or alcohol intake that cannot be reliably quantified.
14. Known or suspected clinically significant allergy to seladelpar or any of its components.
15. Started using UDCA within 6 months prior to screening or adjusted the UDCA dose within 12 weeks prior to screening. Subjects with a history of inadequate response or intolerance to UDCA, as assessed by the trial administrator, are also excluded. Subjects who cannot tolerate UDCA must have received their last dose > 12 weeks prior to screening.
16. Subjects who have received deoxyursolic acid or fibrates (such as bezafibrate, fenofibrate, elafibranor, lanifibranor, pemafibrate, or saroglitazar) within 6 weeks prior to screening.
17. Subjects who have received colchicine, methotrexate, azathioprine, or long-term systemic corticosteroids (> 2 weeks) within 8 weeks prior to screening. For non-hepatic, stable comorbidities, a maximum of prednisone 5 mg or equivalent once daily is permitted.
18. Any long-term treatment with other immunosuppressive therapies (e.g., cyclosporine, tacrolimus, anti-tumor necrosis factor [TNF], or other immunosuppressive biologics) within 6 months prior to screening.
19. Any dose adjustment of antipruritic medications (e.g., cholestyramine, naltrexone, rifampicin, sertraline) for treating pruritus within 1 month prior to screening.
20. Use of contraindicated or concomitant medications. Other medications that affect hepatic or gastrointestinal (GI) function (e.g., drug absorption) may be contraindicated, as determined by the trial administrator on an individual basis. The trial administrator should consult the trial sponsor's medical monitor as needed.
21. Treatment with any other experimental therapy or device within 30 days or 5 half-lives (whichever is longer) prior to screening.
22. Pregnancy and breastfeeding (applicable to women).
23. Having a severe specific infectious pneumonia (COVID-19) infection deemed clinically relevant by the trial administrator during the screening period.
24. Having undergone endoscopic treatment for esophageal or gastric varices within 6 months prior to screening.
The Estimated Number of Participants
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Taiwan
42 participants
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Global
318 participants
