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

Phase 3

Recruiting

• Conditions: Primary Biliary Cholangitis
• Interventions: Drug: Saroglitazar Magnesium 1 mg

• Registration Number: NCT06427395
• Lead Sponsor: Zydus Therapeutics Inc.

Brief Summary

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

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 Timeline

• Study First Submitted: 2024-05-09
• Study First Submitted QC: 2024-05-16
• Study First Posted: 2024-05-23
• Study Start: 2024-07-16
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-27
• Last Update Posted: 2025-03-04
• Primary Completion: 2027-04-18
• Study Completion: 2027-07-18

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Saroglitazar Magnesium 1 mg	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).

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Proportion of participants achieving biochemical response based on the composite endpoints of ALP and total bilirubin	From baseline to Months 12 and 24/EOT	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
Proportion of participants with biochemical response based on the composite endpoints of ALP and total bilirubin	From baseline to Months 12 and 24/EOT	complete normalization of ALP. Change and percent change from baseline in ALP
Time to first occurrence of Liver transplant or placement on a liver transplant list	From baseline to 24 Months/EOT
Time to occurrence of the clinical outcome events in study participants with PBC	From baseline to 24 Months/EOT	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)
Time to the occurrence of Death	From baseline to 24 Months/EOT	Death (liver and non-liver related)
Effect on lipid parameters	From baseline to Months 12 and 24/EOT	Change from baseline in non-HDL-C
Time to occurrence of the clinical outcome events based on Model for End Stage Liver Disease 3.0 score	From baseline to 24 Months/EOT	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
Effect on disease-related symptoms	From baseline to Months 12 and 24/EOT	Change from baseline in Worst Itch NRS (numerical rating scale) scores 0-10, where 0 is no itch and 10 is worst itch imaginable
Effect on liver enzyme parameters	From baseline to Months 12 and 24/EOT	Change from baseline in serum bile acids
Effect on liver stiffness measurement (LSM) assessed by Liver elastography/FibroScan	From baseline to Months 12 and 24/EOT	Change from baseline in LSM assessed by Liver elastography/FibroScan

Trial Locations

Locations (41)

Zydus US007; 🇺🇸 Birmingham, Alabama, United States

Zydus US013; 🇺🇸 Los Angeles, California, United States

Zydus US011; 🇺🇸 Pasadena, California, United States

Zydus US043; 🇺🇸 Sacramento, California, United States

Zydus US022; 🇺🇸 Aurora, Colorado, United States

Zydus US037; 🇺🇸 New Haven, Connecticut, United States

Zydus US027; 🇺🇸 Jacksonville, Florida, United States

Zydus US006; 🇺🇸 Lakewood Ranch, Florida, United States

Zydus US005; 🇺🇸 Miami, Florida, United States

Zydus US020; 🇺🇸 Marietta, Georgia, United States

Zydus US001; 🇺🇸 Indianapolis, Indiana, United States

Zydus US035; 🇺🇸 Rochester, New York, United States

Zydus US002; 🇺🇸 Charlotte, North Carolina, United States

Zydus US015; 🇺🇸 Philadelphia, Pennsylvania, United States

Zydus US004; 🇺🇸 Houston, Texas, United States

Zydus US042; 🇺🇸 Houston, Texas, United States

Zydus US031; 🇺🇸 Murray, Utah, United States

Zydus US016; 🇺🇸 Charlottesville, Virginia, United States

Zydus US039; 🇺🇸 Richmond, Virginia, United States

Zydus US033; 🇺🇸 Seattle, Washington, United States

Zydus AR001; 🇦🇷 Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Zydus AR007; 🇦🇷 Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Zydus AR006; 🇦🇷 Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Zydus AR005; 🇦🇷 Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Zydus AR003; 🇦🇷 Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Zydus AR004; 🇦🇷 Pilar, Buenos Aires, Argentina

Zydus TR014; 🇹🇷 Adana, Turkey

Zydus TR016; 🇹🇷 Altındag, Turkey

Zydus TR004; 🇹🇷 Ankara, Turkey

Zydus TR005; 🇹🇷 Bursa, Turkey

Zydus TR017; 🇹🇷 Cebeci, Turkey

Zydus TR008; 🇹🇷 Gaziantep, Turkey

Zydus TR009; 🇹🇷 Istanbul, Turkey

Zydus TR010; 🇹🇷 Istanbul, Turkey

Zydus TR003; 🇹🇷 Istanbul, Turkey

Zydus TR001; 🇹🇷 Istanbul, Turkey

Zydus TR002; 🇹🇷 Izmir, Turkey

Zydus TR013; 🇹🇷 Izmir, Turkey

Zydus TR011; 🇹🇷 Kocaeli, Turkey

Zydus TR015; 🇹🇷 Melikgazi, Turkey

Zydus TR006; 🇹🇷 Mersin, Turkey