Study of Saroglitazar Magnesium for PBC Patients With Incomplete Response or Intolerant to UDCA Therapy (EPICS-IV)

A Double-blind, Placebo-controlled, Randomized, Phase 3 Study to Evaluate the Efficacy and Safety of Saroglitazar Magnesium on Normalization of Alkaline Phosphatase Levels in Patients With Primary Biliary Cholangitis and an Incomplete Response or Intolerance to Ursodeoxycholic Acid

Study of Saroglitazar Magnesium for PBC Patients with Incomplete Response or Intolerant to UDCA Therapy

Study Overview

• Status: Not yet recruiting
• Conditions: Primary Biliary Cholangitis
• Intervention / Treatment: Drug: Placebo; Drug: Saroglitazar Magnesium 1 mg

Detailed Description

A Double-blind, Placebo-controlled, Randomized, Phase 3 Study to Evaluate the Efficacy of Saroglitazar Magnesium 1 mg on normalization of ALP in patients having ALP > ULN to < 1.67xULN and on Ursodeoxycholic Acid for 12 months or intolerant to Ursodeoxycholic Acid.

• Study Type: Interventional
• Enrollment (Estimated): 89
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Farheen Shaikh; Phone Number: 221 609-730-1900; Email: fshaikh@zydustherapeutics.com
• Study Contact Backup: Name: Deven Parmar; Phone Number: 407 609-703-1900; Email: dparmar@zydustherapeutics.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults between 18 and 80 years of age (both inclusive at screening)
2. History of confirmed Primary Biliary Cholangitis diagnosis
3. Ursodeoxycholic acid treatment for at least 12 months and a stable dose for at least 6 months prior to first screening visit OR intolerant to Ursodeoxycholic acid (last dose of Ursodeoxycholic acid at least 3 months prior to first screening visit).
4. Average Alkaline Phosphatase at both screening Visits 1 and 2: > 1× Upper Limit of Normal and < 1.67× Upper Limit of Normal, and < 30% variance between both levels
5. Total bilirubin ≤ 2 x Upper Limit of Normal at screening (Visit 1), unless there is a prior diagnosis of Gilbert's syndrome. For participants with Gilbert's syndrome, direct bilirubin is to be ≤ 2 x Upper Limit of Normal at screening (Visit 1).
6. Must have given written informed consent (signed and dated).

Exclusion Criteria:

1. Consumption of 14 or more standard alcohol drinks per week if male and 7 or more standard alcohol drink per week if female for at least 3 consecutive months (i.e., 12 consecutive weeks) within 5 years before screening (Note: 1 unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits/hard liquor).
2. History or presence of other concomitant liver diseases at screening
3. Cirrhosis with complications, including history or presence of the following: spontaneous bacterial peritonitis, hepatocellular carcinoma, ascites requiring treatment, encephalopathy, known large esophageal varices, or history of variceal bleeding within one year prior to screening or history of hepatorenal syndrome.
4. Medical conditions that may cause non-hepatic increases in Alkaline Phosphatase (e.g., Paget's disease) or which may diminish life expectancy to < 2 years, including known cancers.
5. Use of obeticholic acid, thiazolidinediones, fibrates (i.e. fenofibrate, bezafibrate, pemafibrate), other Peroxisome Proliferator-Activated Receptor agonists (i.e., seladelpar, elafibranor, lanifibranor), azathioprine, cyclosporine, methotrexate, mycophenolate, pentoxifylline, systemic corticosteroids (equivalent to prednisone dose more than 10 mg per day); potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazid, or nitrofurantoin) (within 12 weeks prior to screening).
6. History of bowel surgery (gastrointestinal [bariatric] surgery in the preceding 1 year or undergoing evaluation for gastrointestinal surgery (bariatric surgery for obesity, extensive small-bowel resection) or orthotopic liver transplant or listed for orthotopic liver transplant.
7. Type 1 diabetes mellitus.
8. Unstable cardiovascular disease
9. History of intracranial hemorrhage, arteriovenous malformation, bleeding disorder, coagulation disorders, or screening blood tests that, in the opinion of the Investigator, indicate clinically significant altered coagulability (e.g., Prothrombin Time, International Normalized Ratio, Activated partial thromboplastin time) at screening.
10. An uncontrolled thyroid disorder
11. History of myopathies or evidence of active muscle disease demonstrated by Creatine Phosphokinase ≥ 5 x Upper Limit of Normal at screening.
12. For subjects with elevated baseline Alanine Aminotransferase or Aspartate Aminotransferase; Alanine Aminotransferase or Aspartate Aminotransferase exceeding by more than 50% on Visit 2 compared to Visit 1.

13. Any of the following laboratory values at screening:

    1. Platelets < 100 × 10^9/L
    2. Albumin < 3.5 g/dL
    3. Estimated Glomerular Filtration Rate < 45 mL/min/1.73 m^2
    4. Alanine Aminotransferase or Aspartate Aminotransferase > 250 U/L
    5. International Normalized Ratio greater than or equal to 1.7. However, participants with an International Normalized Ratio of 1.7 or above may be included if the elevated International Normalized Ratio is not attributable to liver disease.
14. Participation in another interventional clinical study and receipt of any other investigational medication (within 12 weeks prior to randomization up to the end of the study).
15. History of malignancy in the past 5 years and/or active neoplasm except resolved superficial non-melanoma skin cancer.
16. Contraindications to Saroglitazar Magnesium or has any conditions affecting the ability to evaluate the effects of Saroglitazar Magnesium.
17. Known allergy, sensitivity, or intolerance to the study medication, comparator, or formulation ingredients.

18. Pregnancy-related exclusions, including the following:

    1. Pregnant/lactating female (including positive pregnancy test at screening).
    2. Pregnancy should be avoided by male and female participants either by true abstinence or the use of acceptable effective contraceptive measures for the duration of the study and for at least 1 month after the end of the study treatment.
19. History or other evidence of severe illness or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study (such as poorly controlled psychiatric disease, Human Immunodeficiency Virus, coronary artery disease, or active gastrointestinal conditions that might interfere with drug absorption).
20. Cirrhosis with Child-Pugh-Turcotte Class B or C having a score of 7 or above at screening.
21. Participants with Model for End Stage Liver Disease 3.0 score of 12 or above. For participants on anticoagulation medication, baseline International Normalized Ratio determination for Model for End Stage Liver Disease score calculation should take anticoagulant use into account.
22. Initiation or dose adjustment of anti-pruritic drugs (e.g., cholestyramine, naltrexone, rifampin, sertraline, or any investigational therapeutic) within 1 month prior to screening and till randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Saroglitazar Magnesium 1 mg; Saroglitazar magnesium 1 mg, once daily, orally each morning before breakfast	Drug: Saroglitazar Magnesium 1 mg; Saroglitazar magnesium 1 mg once daily, orally each morning before breakfast
Placebo Comparator: Placebo; Matching Placebo once daily, orally each morning before breakfast	Drug: Placebo; Matching Placebo once daily, orally each morning before breakfast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The incidence of participants with ALP ≤ ULN and ≥ 15% decrease from baseline in ALP	Baseline to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of participants with ALP ≤ ULN and ≥ 15% decrease from baseline in ALP		Baseline to Week 4
Change from baseline in the Global PBC Study Group (GLOBE) scores	The GLOBE score is a prognostic scoring system that incorporates various clinical and laboratory parameters to predict the long-term outcome and survival of patients with PBC. Lower GLOBE score predicts lower risk. It is calculated from the following equation: GLOBE score = 0.044378 × age at start of UDCA therapy + 0.93982 × ln(bilirubin × ULN at 1 year follow-up) + 0.335648 × ln(ALP × ULN at 1 year follow-up) - 2.266708 × albumin level × the lower limit of normal (LLN) at 1 year follow-up -0.002581 × platelet count per 10^9/L at 1 year follow-up +1.216865.	Baseline to Week 52
Change from baseline in the United Kingdom Primary Biliary Cholangitis (UK-PBC)	The UK-PBC risk score is a scoring system specifically developed for risk stratification and prognosis in patients with PBC. The higher the score might indicate higher risk to death or live transplantation. UK-PBC risk score = 1 - baseline survival function∧ exp(0.0287854 × [ALP after 12 months of therapy × ULN - 1.722136304] - 0.0422873 × [{(ALT where this was available, otherwise AST, after 12 months of therapy × ULN/10)∧-1} - 8.675729006] + 1.4199 × [ln{bilirubin after 12 months of therapy × ULN/10} + 2.709607778] - 1.960303 × [albumin at baseline × LLN - 1.17673001] - 0.4161954 × [platelet count at baseline × LLN -1.873564875]).	Baseline to Week 52

Collaborators and Investigators

• Sponsor: Zydus Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: December 26, 2025
• First Submitted That Met QC Criteria: February 13, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Primary Biliary Cholangitis; PBC; Saroglitazar Magnesium
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Biliary Tract Diseases; Liver Diseases; Bile Duct Diseases; Fibrosis; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Pathological Conditions, Signs and Symptoms; Liver Cirrhosis, Biliary; saroglitazar
• Other Study ID Numbers: SARO.24.001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No