Saroglitazar Magnesium in the Treatment of Non-Alcoholic Steatohepatitis

NCT03863574 | Completed Phase 2 Results FDA Drug

• 1 other identifier: SARO.17.004
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 6

Brief Summary

This is a randomized, double-blind, placebo-controlled study to evaluate safety and efficacy of Saroglitazar Magnesium 2 mg and 4 mg in patients with NASH. This study will be initiated after obtaining the approvals of Institutional Ethics Committee/Institutional Review Board (IEC/IRB) and the local regulatory authority.

Conditions

Non Alcoholic Steatohepatitis

Keywords

NASH

Outcome Measures

Primary Outcomes (1)

• NAS Score (Nonalcoholic Fatty Liver Disease [NAFLD] Activity Score)

  The primary endpoint is to assess the changes in NAFLD Activity Score (NAS) at week 24 from baseline and with no worsening of fibrosis in NASH patients. NAFLD Activity Score Steatosis \<5% - 0 5% -33% - 1 \>33% -66% - 2 \>66% - 3 Lobular Inflammation No foci - 0 \<2 foci per 200 X field -1 2-4 foci per 200 X field - 2 \>4 foci per 200 X field - 3 Ballooning None - 0 Few balloon cells -1 Many cells/prominent ballooning - 2 Final NAFLD Activity Score = Steatosis Score + Lobular Inflammation Score + Ballooning Score Minimum score for NAS is 0 Maximum score for NAS is 8 Higher score represents the worse disease activity

  Baseline to Week 24

Secondary Outcomes (16)

• To Evaluate the Percentage of Responders in the Treatment Groups.

  Baseline to Week 24

• Percentage of Responders Defined by the Disappearance of Steatohepatitis.

  Baseline to Week 24

• Changes in the Stage of Steatosis, Lobular Inflammation and Ballooning.

  Baseline to Week 24

• Changes in the Stage of Fibrosis.

  Baseline to Week 24

• Changes in the Liver Function Tests; (Alanine Aminotransferase [ALT], Aspartate Aminotransferase [AST], Alkaline Phosphatases [ALP], and Gamma-glutamyl Transferase [GGT]).

  Baseline to Week 24

Study Arms (3)

Saroglitazar Magnesium 2 mg

EXPERIMENTAL

Saroglitazar Magnesium 2 mg tablet orally once daily in the morning before breakfast for 24 weeks.

Drug: Saroglitazar Magnesium 2mg

Saroglitazar Magnesium 4 mg

EXPERIMENTAL

Saroglitazar Magnesium 4 mg tablet orally once daily in the morning before breakfast for 24 weeks.

Drug: Saroglitazar Magnesium 4mg

Placebo

PLACEBO COMPARATOR

Placebo tablet orally once daily in the morning before breakfast for 24 weeks.

Drug: Placebos

Interventions

Saroglitazar Magnesium 2mg DRUG

Patients randomly assigned to this group will receive Saroglitazar Magnesium 2 mg tablet orally once daily for 24 weeks.

Saroglitazar Magnesium 2 mg

Saroglitazar Magnesium 4mg DRUG

Patients randomly assigned to this group will receive Saroglitazar Magnesium 4 mg tablet orally once daily for 24 weeks.

Saroglitazar Magnesium 4 mg

Placebos DRUG

Patients randomly assigned to this group will receive Placebo tablet orally once daily for 24 weeks.

Placebo

Eligibility Criteria

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

You may qualify if:

• Patients able to provide written informed consent for participation in this trial.
• Males or females, 18 to 75 years of age, both inclusive.
• Female must be either of non-child bearing potential (surgically sterilized at least 6 months prior to screening or postmenopausal) or using one or more methods of contraception.
• Histologic confirmation of NASH without cirrhosis (fibrosis stage 0, 1, 2, or 3) from liver biopsy performed either during the screening period or no more than 6 months prior to the first visit, with a NAS of ≥4 and a score of at least 1 in each (steatosis scored 0-3, ballooning scored 0-2, and lobular inflammation scored 0-3). If biopsy was performed within 6 months of screening, the slides, biopsy material or block should be available for baseline documentation. Such patients, whose historical biopsy report is available, should not use medications suspected of having an effect on NASH for at least 3 months prior to the screening.
• BMI ≥25 kg/m\^2.
• For hypertensive patients, blood pressure must be controlled by a stable dose of antihypertensive medications for at least 3 months prior to screening (and the stable dose can be maintained throughout the study)
• Patients with type 2 diabetes mellitus may be included if they fulfil the following criteria;
• Stable therapeutic regimen as defined by no changes in oral agents or dose for at least 3 months before screening and the stable dose can be maintained throughout the study.
• HbA1c ≤ 9.5%
• Patients agree to comply with the study procedure.

You may not qualify if:

• Pregnant and lactating female.
• Positive pregnancy test.
• Patients with history of myopathies or evidence of active muscle diseases.
• Patients with history of alcohol consumption of \>30 gm/day for men, \>20 gm/day for women for consecutive previous 2 years and/or drug abuse.
• Known allergy, sensitivity or intolerance to the study drug or formulation ingredients.
• Participation in an interventional clinical study and/or receipt of any investigational medication within 3 months prior to screening.
• History of malignancy in the past 5 years and/or active neoplasm with the exception of superficial, non-melanoma, skin cancer.
• Any of the following laboratory values at screening:
• Direct bilirubin \>1.5 mg/dL,
• Serum albumin \<2.5 g/dL.
• Estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73m2.
• Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>200 IU/L.
• Patient with international normalized ratio (INR) \>1.5.
• Creatinine kinase ≥ 1.5 upper limit of normal (ULN).
• Lipase ≥ULN.

Sponsors & Collaborators

• Zydus Therapeutics Inc.: lead

Study Sites (6)

Southern Therapy and Advanced Research (STAR) LLC

Jackson, Mississippi, 39216, United States

Location

Gastro One

Germantown, Tennessee, 38138, United States

Location

Digestive Health Research

Hermitage, Tennessee, 37076, United States

Location

Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Clinical Trials of Texas, Inc.

San Antonio, Texas, 78229, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Publications (2)

• Siddiqui MS, Parmar D, Sheikh F, Sarin SK, Cisneros L, Gawrieh S, Momin T, Duseja A, Sanyal AJ. Saroglitazar, a Dual PPAR alpha/gamma Agonist, Improves Atherogenic Dyslipidemia in Patients With Non-Cirrhotic Nonalcoholic Fatty Liver Disease: A Pooled Analysis. Clin Gastroenterol Hepatol. 2023 Sep;21(10):2597-2605.e2. doi: 10.1016/j.cgh.2023.01.018. Epub 2023 Jan 31.

  PMID: 36731585 BACKGROUND

• Siddiqui MS, Idowu MO, Parmar D, Borg BB, Denham D, Loo NM, Lazas D, Younes Z, Sanyal AJ. A Phase 2 Double Blinded, Randomized Controlled Trial of Saroglitazar in Patients With Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol. 2021 Dec;19(12):2670-2672. doi: 10.1016/j.cgh.2020.10.051. Epub 2020 Nov 2.

  PMID: 33152542 RESULT

Related Links

• Siddiqui MS, Parmar D. Saroglitazar, a Dual PPAR alpha/gamma Agonist, Improves Atherogenic Dyslipidemia in Patients With Non-Cirrhotic Nonalcoholic Fatty Liver Disease: A Pooled Anal
• Siddiqui MS, Idowu MO, Parmar D, Borg BB, Denham D, Loo NM, Lazas D, Younes Z, Sanyal AJ. A Phase 2 Double Blinded, Randomized Controlled Trial of Saroglitazar in Patients With Nonalcoholic Steatohepatitis

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

saroglitazar

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Dr Deven Parmar
• Organization: Zydus Therapeutics Inc.

dparmar@zydustherapeutics.com

7324050886

Study Officials

• Deven V Parmar, MD,FACP,FCP

  Zydus Therapeutics Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2019
• First Posted: March 5, 2019
• Study Start: June 12, 2019
• Primary Completion: March 20, 2020
• Study Completion: March 20, 2020
• Last Updated: October 15, 2024
• Results First Posted: October 15, 2024

Record last verified: 2024-09

Locations

US (6)