Saroglitazar Magnesium for Treatment of Primary Biliary Cholangitis

NCT05133336 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: SARO.21.001
• Study Type: interventional
• Target: 196
• Locations: 4 countries
• Sites: 57

Brief Summary

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

Conditions

Primary Biliary Cholangitis

Keywords

Saroglitazar Magnesium; Primary Biliary Cholangitis; PBC

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects with biochemical response based on the composite endpoints of ALP and total bilirubin

  ALP \< 1.67 x ULN, ≥ 15% decrease in ALP relative to baseline, and total bilirubin ≤ ULN or direct bilirubin ≤ ULN in subjects with known Gilbert's syndrome

  From baseline to week 52

Secondary Outcomes (9)

• Proportion of subjects with complete normalization of ALP.

  From baseline to week 52

• Pruritis assessed by 5 D itch scales

  From baseline to Week 24 and Week 52

• Proportion of subjects with biochemical response based on the composite endpoints of ALP and total bilirubin

  From baseline to Weeks 4, 8, 16, and 24.

• Proportion of subjects change from baseline in ALP

  From baseline to Weeks 24 and 52.

• Quality of life assessed by the PBC 40 questionnaire

  From baseline to Weeks 16, 24, and 52.

Study Arms (3)

Saroglitazar Magnesium 2 mg

EXPERIMENTAL

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

Drug: Saroglitazar Magnesium 1 mg; Drug: Saroglitazar Magnesium 2 mg

Saroglitazar Magnesium 1 mg

EXPERIMENTAL

Saroglitazar Magnesium 1 mg tablet orally administered once daily in the morning before breakfast without food, for the duration of treatment (52 weeks).

Drug: Saroglitazar Magnesium 1 mg

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Saroglitazar Magnesium 1 mg 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 1 mg; Saroglitazar Magnesium 2 mg

Placebo DRUG

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

Placebo

Saroglitazar Magnesium 2 mg DRUG

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

Saroglitazar Magnesium 2 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females, between 18 and 75 years of age, both inclusive at screening.
• 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.
• 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
• ALP ≥ 1.67 x ULN at both Visits 1 and 2 and \< 30% variance between the levels from Visit 1 to Visit 2
• Total bilirubin \< 2 x ULN at screening (Visit 1)
• Must provide written informed consent and agree to comply with the trial protocol.

You may not qualify if:

• 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).
• History or presence of other concomitant liver diseases at screening:
• 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)
• Primary sclerosing cholangitis (PSC).
• Alcoholic liver disease.
• 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.
• 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.
• 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).
• 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.

Sponsors & Collaborators

• Zydus Therapeutics Inc.: lead

Study Sites (57)

Zydus US007

Birmingham, Alabama, 35294, United States

Location

Zydus US021

Tucson, Arizona, 85724, United States

Location

Zydus US013

Los Angeles, California, 90048, United States

Location

Zydus US011

Pasadena, California, 91105, United States

Location

Zydus US043

Sacramento, California, 95817, United States

Location

Zydus US022

Aurora, Colorado, 80045, United States

Location

Zydus US037

New Haven, Connecticut, 06510, United States

Location

Zydus US027

Jacksonville, Florida, 32224, United States

Location

Zydus US006

Lakewood Rch, Florida, 34211, United States

Location

Zydus US005

Miami, Florida, 33136, United States

Location

Zydus US028

Sarasota, Florida, 34240, United States

Location

Zydus US019

Tampa, Florida, 33606, United States

Location

Zydus US020

Marietta, Georgia, 30060, United States

Location

Zydus US001

Indianapolis, Indiana, 46202, United States

Location

Zydus US034

Iowa City, Iowa, 52242, United States

Location

Zydus US036

Marrero, Louisiana, 70072, United States

Location

Zydus US023

Rochester, Minnesota, 55905, United States

Location

Zydus US030

St Louis, Missouri, 63104, United States

Location

Zydus US024

Omaha, Nebraska, 68105, United States

Location

Zydus US038

Manhasset, New York, 11030, United States

Location

Zydus US035

Rochester, New York, 14642, United States

Location

Zydus US002

Charlotte, North Carolina, 28204, United States

Location

Zydus US014

Cincinnati, Ohio, 45044, United States

Location

Zydus US015

Philadelphia, Pennsylvania, 19141, United States

Location

Zydus US004

Houston, Texas, 77030, United States

Location

Zydus US042

Houston, Texas, 77030, United States

Location

Zydus US031

Murray, Utah, 84107, United States

Location

Zydus US016

Charlottesville, Virginia, 22908, United States

Location

Zydus US041

Newport News, Virginia, 23602, United States

Location

Zydus US039

Richmond, Virginia, 23219, United States

Location

Zydus US033

Seattle, Washington, 98105, United States

Location

Zydus AR004

Buenos Aires, B1629ODT, Argentina

Location

Zydus AR009

Buenos Aires, B7600FZO, Argentina

Location

Zydus AR001

Buenos Aires, C1118AAT, Argentina

Location

Zydus AR005

Buenos Aires, C1125ABE, Argentina

Location

Zydus AR013

Buenos Aires, C1180AAX, Argentina

Location

Zydus AR007

Buenos Aires, C1199ABB, Argentina

Location

Zydus AR006

Buenos Aires, C1221ADC, Argentina

Location

Zydus AR012

Buenos Aires, C1426ABP, Argentina

Location

Zydus AR003

Buenos Aires, C1430CKE, Argentina

Location

Zydus AR010

Santa Fe, S2002KDS, Argentina

Location

Zydus IS001

Reykjavik, IS-101, Iceland

Location

Zydus TR014

Adana, 01790, Turkey (Türkiye)

Location

Zydus TR016

Altındağ, 06230, Turkey (Türkiye)

Location

Zydus TR004

Ankara, 06800, Turkey (Türkiye)

Location

Zydus TR005

Bursa, 16059, Turkey (Türkiye)

Location

Zydus TR017

Cebeli, 06620, Turkey (Türkiye)

Location

Zydus TR008

Gaziantep, 27080, Turkey (Türkiye)

Location

Zydus TR009

Istanbul, 34093, Turkey (Türkiye)

Location

Zydus TR010

Istanbul, 34098, Turkey (Türkiye)

Location

Zydus TR003

Istanbul, 34764, Turkey (Türkiye)

Location

Zydus TR001

Istanbul, 34899, Turkey (Türkiye)

Location

Zydus TR002

Izmir, 35100, Turkey (Türkiye)

Location

Zydus TR013

Izmir, 35150, Turkey (Türkiye)

Location

Zydus TR011

Kocaeli, 41380, Turkey (Türkiye)

Location

Zydus TR015

Melikgazi, 38030, Turkey (Türkiye)

Location

Zydus TR006

Mersin, 33110, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

saroglitazar

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Deven V Parmar, MD

  Zydus Therapeutics Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind Masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multicenter, Randomized, Double-blind, Placebo controlled, Phase 2b/3 Safety and Efficacy Study . Initially, 192 subjects (64 subjects in each treatment arm) were planned be randomised in a ratio of 1:1:1 in Saroglitazar Magnesium 1 mg, Saroglitazar Magnesium 2 mg, and Placebo arm, respectively. After an optimal dose selection, the subjects are randomised in 2:1 ratio of Saroglitazar Magnesium 1 mg or placebo. There would be approximately 140 evaluable subjects (90 of Saroglitazar 1 mg and 50 of placebo arm)

Study Record Dates

• First Submitted: November 1, 2021
• First Posted: November 24, 2021
• Study Start: April 1, 2022
• Primary Completion: April 30, 2025
• Study Completion: May 7, 2025
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

IC (1); TU (15); AR (10); US (31)