Open-Label Extension Study of Saroglitazar Magnesium in Participants With Primary Biliary Cholangitis

A Multicenter, Open-Label, Extension Clinical Trial to Evaluate Safety and Efficacy of Saroglitazar Magnesium in Participants With Primary Biliary Cholangitis (PBC)

Open-Label Extension Study of Saroglitazar Magnesium in Participants With Primary Biliary Cholangitis

Study Overview

• Status: Active, not recruiting
• Conditions: Primary Biliary Cholangitis
• Intervention / Treatment: Drug: Saroglitazar Magnesium 1 mg

Detailed Description

A Multicenter, Open-Label, Extension Clinical trial to evaluate Safety and Efficacy of Saroglitazar Magnesium in Participants with Primary Biliary Cholangitis (PBC)

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1118AAT
      • Zydus AR001
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1199ABB
      • Zydus AR007
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1221ADC
      • Zydus AR006
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1425BGC
      • Zydus AR005
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1430CKE
      • Zydus AR003
    • Pilar, Buenos Aires, Argentina, B1629ODT
      • Zydus AR004
• Turkey (Türkiye)
  • Altındağ, Turkey (Türkiye), 06230
    • Zydus TR016
  • Ankara, Turkey (Türkiye), 06800
    • Zydus TR004
  • Bursa, Turkey (Türkiye), 16059
    • Zydus TR005
  • Cebeli, Turkey (Türkiye), 06620
    • Zydus TR017
  • Melikgazi, Turkey (Türkiye), 38039
    • Zydus TR015
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Zydus US013
    • Pasadena, California, United States, 91105
      • Zydus US011
    • Sacramento, California, United States, 95817
      • Zydus US043
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Zydus US022
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Zydus US037
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Zydus US027
    • Lakewood Rch, Florida, United States, 34211
      • Zydus US006
    • Miami, Florida, United States, 33136
      • Zydus US005
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Zydus US020
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Zydus US001
  • New York
    • Rochester, New York, United States, 14642
      • Zydus US035
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Zydus US002
  • Texas
    • Houston, Texas, United States, 77030
      • Zydus US042
  • Utah
    • Murray, Utah, United States, 84107
      • Zydus US031
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Zydus US016
    • Richmond, Virginia, United States, 23298
      • Zydus US039
  • Washington
    • Seattle, Washington, United States, 98105
      • Zydus US033

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Must provide written informed consent and agree to comply with the trial protocol
2. Participated and completed SARO.21.001, the double-blind treatment phase study

Exclusion Criteria:

1. Consumption of 2 standard drinks per day if male and 1 standard drink per day if female for 3 consecutive months (12 consecutive weeks) throughout double-blind phase till screening.
2. Participants with MELD 3.0 score of 15 or greater

3. History or presence of other concomitant liver diseases at screening:

   1. Chronic hepatitis B or C virus (HBV, HCV) infection
   2. Primary sclerosing cholangitis (PSC)
   3. Alcoholic liver disease
   4. Autoimmune hepatitis (AIH)-PBC overlap syndrome
   5. Hemochromatosis
   6. Non-alcoholic steatohepatitis (NASH) on historical biopsy
4. Cirrhosis with complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma, uncontrolled ascites, encephalopathy, history of variceal bleeding or history of hepatorenal syndrome at screening.
5. Use of Thiazolidinediones or Fibrates (within 12 weeks prior to screening)
6. Use of other PPAR agonists (i.e., Elafibranor, Seladelpar), Obeticholic acid (OCA), methotrexate, budesonide and other systemic corticosteroids (Prednisone dose more than 10 mg); potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazid, or nitrofurantoin) (within 12 weeks prior to screening)
7. 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 (OLT) or listed for OLT

8. Unstable cardiovascular disease, including:

   1. Unstable angina, (i.e., new or worsening symptoms of coronary heart disease in the 12 weeks before screening and throughout the screening period), acute coronary syndrome in the 24 weeks before screening and throughout the screening period, acute myocardial infarction in the 12 weeks before screening and throughout the screening period or heart failure of New York Heart Association class (III - IV) or worsening congestive heart failure, or coronary artery intervention, in the 24 weeks before screening and throughout the screening period
   2. History/current unstable cardiac dysrhythmias
   3. Uncontrolled hypertension at screening
   4. Stroke or transient ischemic attack in the 24 weeks before screening
9. History of intracranial hemorrhage, arteriovenous malformation, bleeding disorder, and coagulation disorders

10. An uncontrolled thyroid disorder

    1. Uncontrolled hyperthyroidism: defined as any history of hyperthyroidism that has either not been treated with either radioactive iodine and/or surgery or that has been treated with radioactive iodine and/or surgery, but has required ongoing continuous or intermittent use of thyroid hormone synthesis inhibitors (i.e., methimazole or propylthiouracil) in the 24 weeks before screening
    2. Uncontrolled hypothyroidism: defined as initiation of thyroid hormone replacement therapy or dose adjustment of replacement therapy in the 12 weeks before screening
11. History of myopathies or evidence of active muscle disease demonstrated by CPK ≥ 5 × ULN at screening

12. Any of the following laboratory values:

    1. Total bilirubin > 3 x ULN
    2. Platelets < 50 × 103/mL
    3. Albumin < 2.8 g/dL
    4. eGFR < 45 mL/min/1.73 m2
    5. ALT or AST > 250 U/L
    6. ALP > 10 × ULN
13. Participation in another interventional clinical study and receipt of any other investigational medication or medical device within 30 days or within 5 half-lives, whatever is longer, prior to screening
14. History of malignancy in the past 5 years and/or active neoplasm which may diminish life expectancy (except resolved superficial non-melanoma skin cancer, carcinomas in situ or other stable, relatively benign conditions if appropriately treated prior to screening)
15. Known allergy, sensitivity or intolerance to the study medication or formulation ingredients

16. Pregnancy-related exclusions, including:

    1. Pregnant/lactating female (including positive pregnancy test at screening)
    2. Participants agree to avoid pregnancy either by true abstinence or the use of an acceptable effective contraceptive measures for the duration of the study and for at least 1 month after the end of the study medication. Refer Appendix 9 Contraceptive Guidance.
17. 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, HIV, coronary artery disease or active gastrointestinal conditions that might interfere with drug absorption)
18. Cirrhosis with Child-Pugh-Turcotte (CPT) class B or C having score of 7 or above at screening (Refer Appendix 11

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Saroglitazar Magnesium 1 mg; Saroglitazar Magnesium 1 mg tablet orally administered once daily in the morning before breakfast without food, for the duration of treatment (24 months).	Drug: Saroglitazar Magnesium 1 mg; Saroglitazar Magnesium 1 mg will be assigned to all participants enrolled in the open label extension program

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	From baseline to 24 Months/EOT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants achieving biochemical response based on the composite endpoints of ALP and total bilirubin	ALP < 1.67 x ULN, ≥ 15% decrease in ALP, and total bilirubin ≤ ULN or direct bilirubin ≤ ULN relative to baseline in participants with known Gilbert's syndrome	From baseline to Months 12 and 24/EOT
Proportion of participants with biochemical response based on the composite endpoints of ALP and total bilirubin	complete normalization of ALP. Change and percent change from baseline in ALP	From baseline to Months 12 and 24/EOT
Time to occurrence of the clinical outcome events in study participants with PBC	Defined as new onset or recurrence of any of the following: Hospitalization for new onset or recurrence of variceal bleed; Hepatic encephalopathy (as defined by a West Haven score ≥2); New onset ascites requiring treatment; Refractory ascites (requiring large volume paracentesis); Spontaneous bacterial peritonitis (confirmed by culture from diagnostic paracentesis)	From baseline to 24 Months/EOT
Time to occurrence of the clinical outcome events based on Model for End Stage Liver Disease 3.0 score	Time from enrolment to the first occurrence of Model for End Stage Liver Disease 3.0 score ≥ 15 and 25% increase from baseline as measured on 2 consecutive occasions performed at least two weeks apart with no competing etiologies identified	From baseline to 24 Months/EOT
Time to first occurrence of Liver transplant or placement on a liver transplant list		From baseline to 24 Months/EOT
Time to the occurrence of Death	Death (liver and non-liver related)	From baseline to 24 Months/EOT
Effect on liver enzyme parameters	Change from baseline in ALT	From baseline to Months 12 and 24/EOT
Effect on liver enzyme parameters	Change from baseline in AST	From baseline to Months 12 and 24/EOT
Effect on liver enzyme parameters	Change from baseline in GGT	From baseline to Months 12 and 24/EOT
Effect on liver enzyme parameters	Change from baseline in total bilirubin	From baseline to Months 12 and 24/EOT
Effect on lipid parameters	Change from baseline in TG	From baseline to Months 12 and 24/EOT
Effect on lipid parameters	Change from baseline in LDL-C	From baseline to Months 12 and 24/EOT
Effect on lipid parameters	Change from baseline in HDL-C	From baseline to Months 12 and 24/EOT
Effect on lipid parameters	Change from baseline in VLDL-C	From baseline to Months 12 and 24/EOT
Effect on lipid parameters	Change from baseline in total cholesterol	From baseline to Months 12 and 24/EOT
Effect on lipid parameters	Change from baseline in non-HDL-C	From baseline to Months 12 and 24/EOT
Effect on liver enzyme parameters	Change from baseline in serum bile acids	From baseline to Months 12 and 24/EOT
Effect on liver stiffness measurement (LSM) assessed by Liver elastography/FibroScan	Change from baseline in LSM assessed by Liver elastography/FibroScan	From baseline to Months 12 and 24/EOT
Effect on disease-related symptoms	Change from baseline in quality of life (Primary Biliary Cholangitis- 40) questionnaire domains Scale as Never, Rarely, Sometimes, Most of the time, and Always	From baseline to Months 12 and 24/EOT
Effect on disease-related symptoms	Change from baseline in 5-D itch scale Score ranging from 5 to 25, where higher score represents worst itching	From baseline to Months 12 and 24/EOT
Effect on disease-related symptoms	Change from baseline in Worst Itch NRS (numerical rating scale) scores 0-10, where 0 is no itch and 10 is worst itch imaginable	From baseline to Months 12 and 24/EOT

Collaborators and Investigators

• Sponsor: Zydus Therapeutics Inc.
• Investigators: Study Director: Deven Parmar, Zydus Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2024
• Primary Completion (Estimated): April 18, 2027
• Study Completion (Estimated): July 18, 2027

Study Registration Dates

• First Submitted: May 9, 2024
• First Submitted That Met QC Criteria: May 16, 2024
• First Posted (Actual): May 23, 2024

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.23.002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No