Saroglitazar Magnesium for Treatment of Primary Biliary Cholangitis

NCT ID: NCT05133336

Last Updated: 2025-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 196 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-01
• Study Completion Date: 2025-05-07

Brief Summary

Saroglitazar Magnesium 1 mg and 2 mg tablets for treatment of subjects with Primary Biliary Cholangitis (PBC)

Detailed Description

A Multicenter, Randomized, Double-blind, Placebo controlled, Phase 2b/3 Study to Evaluate the Efficacy and Safety of Saroglitazar Magnesium in Subjects with Primary Biliary Cholangitis

Conditions

Primary Biliary Cholangitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Saroglitazar Magnesium 2 mg

Subjects who received Saroglitazar Magnesium 2 mg tablet orally administered once daily in the morning before breakfast are switched to Saroglitazar Magnesium 1 mg for remaining of the treatment period

Group Type: EXPERIMENTAL

Saroglitazar Magnesium 1 mg

Intervention Type: DRUG

Subjects randomized to Saroglitazar Magnesium 1 mg arm will receive Saroglitazar Magnesium 1 mg treatment for the entire treatment period up to Week 52.

Saroglitazar Magnesium 2 mg

Intervention Type: DRUG

Subjects randomized to Saroglitazar Magnesium 2 mg arm are switched to Saroglitazar Magnesium 1 mg treatment up to Week 52

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 (52 weeks).

Group Type: EXPERIMENTAL

Saroglitazar Magnesium 1 mg

Intervention Type: DRUG

Subjects randomized to Saroglitazar Magnesium 1 mg arm will receive Saroglitazar Magnesium 1 mg treatment for the entire treatment period up to Week 52.

Placebo

Placebo tablet orally administered once daily in the morning before breakfast without food, for the duration of treatment (52 weeks).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Subjects randomized to placebo arm will receive placebo treatment for the entire treatment period up to Week 52.

Interventions

Saroglitazar Magnesium 1 mg

Subjects randomized to Saroglitazar Magnesium 1 mg arm will receive Saroglitazar Magnesium 1 mg treatment for the entire treatment period up to Week 52.

Intervention Type: DRUG

Saroglitazar Magnesium 2 mg

Subjects randomized to Saroglitazar Magnesium 2 mg arm are switched to Saroglitazar Magnesium 1 mg treatment up to Week 52

Intervention Type: DRUG

Placebo

Subjects randomized to placebo arm will receive placebo treatment for the entire treatment period up to Week 52.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Males or females, between 18 and 75 years of age, both inclusive at screening.

2. Subjects on ursodeoxycholic acid (UDCA) for at least 12 months at a therapeutic dose (at least 13 mg/kg per day) and a stable dose for 6 months prior to Screening Visit and having ALP ≥ 1.67 x ULN.

OR Subjects who are unable to tolerate UDCA and did not receive UDCA for at least 3 months prior to the date of screening and having ALP ≥ 1.67 x ULN.

3. History of confirmed PBC diagnosis, based on American Association for the Study of Liver Disease [AASLD] and European Association for Study of the Liver [EASL] Practice Guidelines, as demonstrated by the presence of at least ≥ 2 of the following 3 diagnostic factors:

• History of elevated ALP levels for at least 6 months prior to screening
• Positive anti-mitochondrial antibodies (AMA) titer OR positive PBC specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components [PDC-E2, 2-oxo-glutaric acid dehydrogenase complex]) if AMA is negative
• Liver biopsy consistent with PBC

4. ALP ≥ 1.67 x ULN at both Visits 1 and 2 and < 30% variance between the levels from Visit 1 to Visit 2

5. Total bilirubin < 2 x ULN at screening (Visit 1)

6. Must provide written informed consent and agree to comply with the trial protocol.

Exclusion Criteria

1. Consumption of 2 standard alcohol drinks per day if male and 1 standard alcohol drink per day if female for at least 3 consecutive months (12 consecutive weeks) within 5 year 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:

1. Chronic hepatitis B or C virus (HBV, HCV) infection. (Note: However, If the subject has been treated for the HCV infection and has been cured for a duration of more than 2 years from screening, such subjects can be enrolled in the study)

2. Primary sclerosing cholangitis (PSC).

3. Alcoholic liver disease.

4. Autoimmune hepatitis (AIH) indicative of PBC with overlap syndrome.

Note: The Paris criteria are commonly used to define the presence of PBC with features of AIH and have been endorsed by EASL and AASLD. According to these criteria, a diagnosis can be made in a patient with PBC as follows:

At least two of the following:

I. ALP > 2 x ULN or GGT > 5 x ULN. II. AMA positive III. Florid bile duct lesion on histology. AND

At least two of the following three features:

I. ALT > 5 x ULN. II. Immunoglobulin G serum levels > 2 x ULN or smooth muscle autoantibody positive.

III. Moderate to severe interface hepatitis on histology. e. Hemochromatosis. f. Non-alcoholic steatohepatitis (NASH) on historical biopsy. 3.Cirrhosis with complications, including history or presence of: 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.

5.Medical conditions that may cause non-hepatic increases in ALP (e.g., Paget's disease) or which may diminish life expectancy to < 2 years, including known cancers.

6.Use of thiazolidinediones or fibrates (within 12 weeks prior to screening). 7.Use of obeticholic acid (OCA), azathioprine, cyclosporine, methotrexate, mycophenolate, pentoxifylline, budesonide and other systemic corticosteroids (Note: Prednisone dose should not be 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).

9.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.

10.Type 1 diabetes mellitus. 11.Unstable cardiovascular disease, including:

a. 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.

b. History/current unstable cardiac dysrhythmias. c. Uncontrolled hypertension at screening. d. Stroke or transient ischemic attack in the 24 weeks before screening. 12.History of intracranial hemorrhage, arteriovenous malformation, bleeding disorder, coagulation disorders, or screening blood tests that, in the opinion of the Investigator, indicate altered coagulability (e.g., PT, INR, aPTT) at screening.

13.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.

14.History of myopathies or evidence of active muscle disease demonstrated by CPK ≥ 5 x ULN at screening.

15.Subjects whose ALT, AST, or ALP exceeds by more than 50% on Visit 2 reading compared to Visit 1. Note: If the ALT, AST, or ALP values on Visit 2 exceed by more than 50% from Visit 1, then a third value will be measured (within 1- 2 weeks) to assess for the trend. If the third value shows continued increase ≥ 10%, then subject is considered ineligible for randomization.

16.Any of the following laboratory values at screening:

a. Platelets < 50 × 109/L b. Albumin < 2.8 g/dL c. eGFR < 45 mL/min/1.73 m2 d. ALP > 10 x ULN e. ALT or AST > 250 U/L 17.Participation in another interventional clinical study and receipt of any other investigational medication (within 12 weeks prior to randomization up to end of study).

18.History of malignancy in the past 5 years and/or active neoplasm with the exception of resolved superficial non-melanoma skin cancer.

19.Contraindications to Saroglitazar Magnesium or has any conditions affecting the ability to evaluate the effects of Saroglitazar Magnesium.

20.Known allergy, sensitivity, or intolerance to the study drug, comparator, or formulation ingredients.

21.Pregnancy-related exclusions, including:

a. Pregnant/lactating female (including positive pregnancy test at screening). b. Pregnancy should be avoided by male and female subjects 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 treatment. Refer Appendix 8 Contraceptive Guidance 22.History or other evidence of severe illness or any other conditions that would make the subject, 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).

23.Cirrhosis with Child-Pugh-Turcotte (CPT) Class B or C having score of 7 or above at screening 24.Subjects with Model for End Stage Liver Disease (MELD 3.0) score of 12 or above

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zydus Therapeutics Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Deven V Parmar, MD

Role: STUDY_DIRECTOR

Zydus Therapeutics Inc.

Locations

Zydus US007

Birmingham, Alabama, United States

Zydus US021

Tucson, Arizona, 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 Rch, Florida, United States

Zydus US005

Miami, Florida, United States

Zydus US028

Sarasota, Florida, United States

Zydus US019

Tampa, Florida, United States

Zydus US020

Marietta, Georgia, United States

Zydus US001

Indianapolis, Indiana, United States

Zydus US034

Iowa City, Iowa, United States

Zydus US036

Marrero, Louisiana, United States

Zydus US023

Rochester, Minnesota, United States

Zydus US030

St Louis, Missouri, United States

Zydus US024

Omaha, Nebraska, United States

Zydus US038

Manhasset, New York, United States

Zydus US035

Rochester, New York, United States

Zydus US002

Charlotte, North Carolina, United States

Zydus US014

Cincinnati, Ohio, 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 US041

Newport News, Virginia, United States

Zydus US039

Richmond, Virginia, United States

Zydus US033

Seattle, Washington, United States

Zydus AR004

Buenos Aires, , Argentina

Zydus AR009

Buenos Aires, , Argentina

Zydus AR001

Buenos Aires, , Argentina

Zydus AR005

Buenos Aires, , Argentina

Zydus AR013

Buenos Aires, , Argentina

Zydus AR007

Buenos Aires, , Argentina

Zydus AR006

Buenos Aires, , Argentina

Zydus AR012

Buenos Aires, , Argentina

Zydus AR003

Buenos Aires, , Argentina

Zydus AR010

Santa Fe, , Argentina

Zydus IS001

Reykjavik, , Iceland

Zydus TR014

Adana, , Turkey (Türkiye)

Zydus TR016

Altındağ, , Turkey (Türkiye)

Zydus TR004

Ankara, , Turkey (Türkiye)

Zydus TR005

Bursa, , Turkey (Türkiye)

Zydus TR017

Cebeli, , Turkey (Türkiye)

Zydus TR008

Gaziantep, , Turkey (Türkiye)

Zydus TR009

Istanbul, , Turkey (Türkiye)

Zydus TR010

Istanbul, , Turkey (Türkiye)

Zydus TR003

Istanbul, , Turkey (Türkiye)

Zydus TR001

Istanbul, , Turkey (Türkiye)

Zydus TR002

Izmir, , Turkey (Türkiye)

Zydus TR013

Izmir, , Turkey (Türkiye)

Zydus TR011

Kocaeli, , Turkey (Türkiye)

Zydus TR015

Melikgazi, , Turkey (Türkiye)

Zydus TR006

Mersin, , Turkey (Türkiye)

Countries

United States; Argentina; Iceland; Turkey (Türkiye)

Other Identifiers

SARO.21.001

Identifier Type: -

Identifier Source: org_study_id