Treatment for liver impairment in patients with cirrhosis from cholestatic liver disease

A Phase 1, Open-Label Extension Groups Study in Subjects Having Hepatic Impairment With Cirrhosis Due to Cholestatic Liver Disease

This study is testing a new medication called Saroglitazar Magnesium to see if it can improve liver function and health in people with cirrhosis from cholestatic liver disease.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Zydus Therapeutics Inc. (Industry-sponsored)
• Locations: 1 site (Indianapolis, Indiana)
• Trial ID: NCT05045482 on ClinicalTrials.gov

What this trial studies

This Phase 1 open-label extension study investigates the effects of Saroglitazar Magnesium in patients suffering from hepatic impairment due to cirrhosis caused by cholestatic liver disease. Participants will receive either 1 mg or 2 mg doses of the medication, with the aim of assessing its safety and efficacy. The study is designed to gather data on the drug's impact on liver function and overall health in this specific patient population. It includes a thorough screening process to classify participants based on their hepatic impairment severity.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 80 with documented hepatic impairment and cirrhosis from cholestatic liver disease.

Not a fit: Patients with hepatic impairment not related to cholestatic liver disease or those with severe comorbid conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve liver function and quality of life for patients with cirrhosis due to cholestatic liver disease.

How similar studies have performed: While this approach is being explored in this specific context, similar studies have shown promise in treating hepatic impairment with targeted therapies.

Eligibility criteria

Inclusion Criteria:

For all subjects:

1. Ability to comprehend and willingness to sign a written ICF for the study.
2. Male or female aged 18 to 80 years (inclusive) at the time of signing the ICF.
3. Body mass index within the range 18.0 to 48.0 kg/m2 (inclusive) at screening.
4. Females must be non-pregnant, non-lactating and of non-childbearing potential or using highly efficient contraception for the full duration of the study.
5. Females of child-bearing potential and males must agree to use contraception for the full duration of the study.
6. Ability to swallow and retain oral medication.

   For Subjects in Groups 8 and 9 (Hepatic impairment group but with cirrhosis from cholestatic liver disease):
7. Participants having documented history of hepatic impairment with cirrhosis due to cholestatic liver disease in Groups 8 and 9 will be classified in sub groups at screening based on CPT score. If the hepatic impairment classification for the subject is not the same at screening and Day -1, enrolment of the subject into a hepatic category group will be at the discretion of the hepatology Investigator.
8. Laboratory test values for hepatic impairment subjects Groups 8 (8A, 8B, 8C) and 9 (9A, 9B, 9C) must be clinically acceptable to the Investigator and meet all the following parameters at Screening:

   1. ALT/AST value ≤ 10 × upper limit of normal (ULN)
   2. Absolute neutrophil count (ANC) ≥ 750/mm3
   3. Platelets ≥ 25,000/mm3
   4. Hemoglobin ≥ 8 g/dL
   5. α-fetoprotein \< 50 ng/mL or 50-80 ng/mL with negative imaging study (US, CT, MRI).

   For Subjects in Groups 8D and 9D (normal hepatic function groups):
9. Subjects should be in good health as determined by no clinically significant findings in the medical history, physical examination, vital signs, 12-lead electrocardiograms (ECGs), or laboratory examinations at Screening or Check-in.
10. Laboratory test values within normal limits or considered not clinically significant by the Investigator for subjects with normal hepatic function including ALT/AST \< 1.2 × ULN at screening.

Exclusion Criteria:

For all subjects:

1. Any significant, unstable medical condition or other instability that would prevent the subject from participating in the study as determined by the Investigator or designee.
2. History of malignancy of any type in the last 3 years of screening, with the exception of the following: in situ cervical or breast cancer or surgically excised non-melanoma skin cancers (i.e. basal cell or squamous cell carcinoma).
3. History of stomach or intestinal surgery or resection within the six months prior to screening that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy, cholecystectomy, and hernia repair will be allowed).
4. History of any significant drug allergy (such as anaphylaxis) deemed clinically relevant by the Investigator.
5. Any major surgery within 3 months of screening.
6. Donation of blood or blood products within 3 months prior to screening.
7. Current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment or symptoms of active infectious disease within the two weeks prior to screening.
8. Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's Wort, within 21 days prior to screening, unless deemed acceptable by the Investigator.
9. Receiving or has received any investigational drug within the 30 days or 5 half-lives (whichever is longer), before receiving Saroglitazar Magnesium.
10. Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73m2 by modification of diet in renal disease (MDRD) formula at screening.
11. Positive alcohol breath test at the time of check-in or those subjects who have current alcohol or substance abuse judged by the Investigator to potentially interfere with subject compliance or subject safety.
12. Positive test for drugs of abuse at screening or admission. Subjects with a positive test based on a prescribed medication may be enrolled.
13. Any subject with poor peripheral venous access
14. Receipt of blood products within 1 month prior to check in.
15. Human immunodeficiency virus (HIV) type 1 antibody positive at screening for all groups.

    For Subjects in Groups 8 and 9 (Hepatic impairment group but with cirrhosis from cholestatic liver disease):
16. Other known cause of liver disease such as NASH, alcoholic steatohepatitis (ASH), autoimmune hepatitis, or acute or chronic viral hepatitis as determined by the Investigator and subject's medical records.
17. Subjects who have had a change in hepatic disease status within 30 days of screening, as documented by the participant's medical history and deemed clinically significant by the Investigator.
18. Subjects having -

    1. History of gastrointestinal bleeding within 1 month prior to screening.
    2. Current functioning organ transplant.
    3. Evidence of severe ascites requiring frequent paracentesis in the opinion of investigator.
19. Subjects who use or intend to use any over the counter (vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) or prescription medications within 30 days or 5 half-lives (whichever is longer) prior to enrolment, with the exception of hormone replacement therapy and therapies for hepatic disease and treatments of associated disorders that have been stable for at least 30 days prior to screening and until Day 1, unless deemed acceptable by the Investigator (or designee).

    For Subjects in Group 8A (Mild hepatic impairment group) and 8B (Moderate impairment group)
20. Total bilirubin \> 5×ULN

    For Control with Normal Hepatic Function:
21. Subjects who have taken any prescription medications or over-the-counter medications, including herbal products, within 14 days prior to start of study drug dosing, with the exception of vitamins, acetaminophen, hormonal contraceptive medications and/or any other over-the-counter product approved by the Investigator.

Where this trial is running

Indianapolis, Indiana

• Zydus US002 — Indianapolis, Indiana, United States (Recruiting)

Study contacts

• Study coordinator: Farheen Shaikh

Conditions Hepatic Impairment; Cirrhosis; Cholestatic Liver Disease; Saroglitazar Magnesium