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Non Alcoholic SteatohepatitisPhase 2EVIDENCES VINCT03863574

Saroglitazar Magnesium in the Treatment of Non-Alcoholic Steatohepatitis

A Phase 2 study testing Saroglitazar Magnesium 2mg and Saroglitazar Magnesium 4mg in people with Non Alcoholic Steatohepatitis, run by Zydus Therapeutics Inc. at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Non Alcoholic Steatohepatitis
What is being tested?
Saroglitazar Magnesium 2mg and Saroglitazar Magnesium 4mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
16 participants
Where
6 sitesUnited States
Study dates
12 Jun 2019to 20 Mar 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Amylase ≥ ULN.
  • Unstable cardiovascular disease, including:
  • unstable angina, (i.e., new or worsening symptoms of coronary heart disease within the 3 months preceding screening), acute coronary syndrome within the 6 months preceding Screening, acute myocardial infarction within the 3 months preceding screening or heart failure of New York Heart Association class (III - IV) or worsening congestive heart failure, or coronary artery intervention, within the 6 months preceding screening
  • history of (within 3 months preceding Screening) or current unstable cardiac dysrhythmias
  • uncontrolled hypertension (systolic blood pressure [BP] > 155 mmHg and/or diastolic BP > 95 mmHg)
  • Stroke or transient ischemic attack within the 6 months preceding screening.
  • Previous history of bladder disease and/or hematuria.
  • Previous liver biopsy that demonstrated presence of cirrhosis or radiologic imaging consistent with cirrhosis or portal hypertension.
  • Type 1 diabetes mellitus.
  • Use of drugs that are known Cytochrome P4502C8 (CYP2C8) inhibitors/substrate.
  • Use of drugs associated with a clinical or histological picture consistent with fatty liver disease or NASH for more than 12 consecutive weeks in the 1 year prior to start of the study; (these include amiodarone, tamoxifen, methotrexate, glucocorticoids, anabolic steroids, tetracyclines, estrogens, valproate/valproic acid, chloroquine, anti-HIV drugs).
  • History of thyroid disease (hypothyroid patients who are euthyroid on thyroid hormone replacement can be included).
  • History of, or current, cardiac dysrhythmias.
  • History of bariatric surgery, or undergoing evaluation for bariatric surgery.
  • Patients with a >10% weight loss in the 3 months prior to screening.
  • History or other evidence of severe illness or any other conditions that would make the patient, in the opinion of the Investigator, unsuitable for the study (such as poorly controlled psychiatric disease, coronary artery disease, HIV or active gastrointestinal conditions that might interfere with drug absorption).
  • Patients on any treatment with other drugs used for treatment of NASH [pentoxyphyllin, ursodeoxycholic acid, antioxidants such as vitamin E (>800 IU/day), glutathione, orlistat, betaine, incretin mimetics or non-prescribed complementary alternative medications (including dietary supplements, megadose vitamins, herbal preparations and special teas)] or any medicine in clinical trials for NASH. (However, patients who are taking stable dose of vitamin E for at least 3 months prior to screening will be enrolled in the study).
  • History of other causes of chronic liver disease [autoimmune, primary biliary cirrhosis, hepatitis B virus (HBV) and hepatitis C virus (HCV), Wilson disease, alpha-1-antitrypsin deficiency, hemochromatosis etc.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Gastro One

    Germantown, Tennessee, 38138

  • Digestive Health Research

    Hermitage, Tennessee, 37076

  • Southern Therapy and Advanced Research (STAR) LLC

    Jackson, Mississippi, 39216

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • Texas Liver Institute

    San Antonio, Texas, 78215

  • Clinical Trials of Texas, Inc.

    San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: A Phase 2, Prospective, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Saroglitazar Magnesium 2 mg and 4 mg in Patients With Non-alcoholic Steatohepatitis (NASH)

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.

Read the detailed description

Patients clinically suspected of NASH will be invited for a screening programme for inclusion in the study. Patients will be screened according to the inclusion and exclusion criteria. Clinical evaluation will be conducted for baseline characteristics and anthropometry measurements such as body weight and height.

After clinical evaluations, all baseline safety and efficacy parameters will be recorded as per Visit Schedule. All laboratory collections will be performed following overnight fasting (at least 8 hrs).

Following confirmation of all clinical and laboratory inclusion and exclusion criteria, patients will continue into the screening period. During the screening period liver biopsy will be performed. However, if a biopsy was performed within 6 months the slides and biopsy material, or block, must be made available for baseline documentation. Such Patients, whose historical biopsy report is available, should not use medication suspected of having an effect on NASH from the 3 months prior to the screening.

Liver biopsy will be performed to confirm the diagnosis of NASH and record a baseline Non-alcoholic fatty liver disease (NAFLD) Activity Score (NAS). The histological evidence of NASH is defined as NAS ≥ 4 with a minimum score of 1 for all of its three components [steatosis, hepatocyte ballooning and lobular inflammation].

Following confirmation of inclusion/exclusion criteria and upon histological confirmation of NASH by liver biopsy, patients will be enrolled into the study.

Eligible patients will be randomly assigned to receive Saroglitazar Magnesium 2 mg or 4 mg or placebo in a 2:2:1 ratio for 24 weeks.

Upon completion of 24 weeks of treatment, liver biopsy will be performed and the NAFLD Activity Score recorded.

Being tested
Saroglitazar Magnesium 2mg, Saroglitazar Magnesium 4mg, Placebos
Keywords
NASH
Medical subject headings
Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Saroglitazar Magnesium 2mgDrug

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

  • Saroglitazar Magnesium 4mgDrug

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

  • PlacebosDrug

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

Study groups in NCT03863574
Study groupRoleWhat they receive
Saroglitazar Magnesium 2 mgExperimentalSaroglitazar Magnesium 2 mg tablet orally once daily in the morning before breakfast for 24 weeks.
Receives: Drug: Saroglitazar Magnesium 2mg
Saroglitazar Magnesium 4 mgExperimentalSaroglitazar Magnesium 4 mg tablet orally once daily in the morning before breakfast for 24 weeks.
Receives: Drug: Saroglitazar Magnesium 4mg
PlaceboPlacebo comparatorPlacebo tablet orally once daily in the morning before breakfast for 24 weeks.
Receives: Drug: Placebos

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Baseline to Week 24

Secondary outcomes (16)

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

    Responder is defined as a decrease from baseline of at least 2 points spread across at least 2 of the NAS components [steatosis, hepatocyte ballooning, and lobular inflammation] with no worsening of fibrosis.

    Measured: Baseline to Week 24

  2. Percentage of Responders Defined by the Disappearance of Steatohepatitis.

    Percentage of responders defined by the disappearance of steatohepatitis

    Measured: Baseline to Week 24

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

    Changes in the stage of steatosis, lobular inflammation and ballooning by evaluating the NAS Score (Nonalcoholic fatty liver disease 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 Higher score represents the worse disease activity

    Measured: Baseline to Week 24

  4. Changes in the Stage of Fibrosis.

    Changes in the stage of fibrosis by evaluating the Fibrosis stages

    Fibrosis Score

    Definition None - 0 Perisinusoidal or periportal - 1 Mild, zone 3, perisinusoidal - 1A Moderate, zone3, perisinusoidal -1B Portal/periportal -1C Perisinusoidal and portal/periportal - 2 Bridging fibrosis - 3 Cirrhosis - 4 Higher score represents the worse disease activity

    Measured: Baseline to Week 24

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

    Liver function tests include ALT, AST, ALP, GGT

    Measured: Baseline to Week 24

  6. Changes in the Liver Function Tests; Albumin and Total Protein

    Changes in albumin and total protein

    Measured: Baseline to Week 24

  7. Changes in the Liver Function Tests; Direct Bilirubin

    Change in direct bilirubin

    Measured: Baseline to Week 24

  8. Changes in the Lipid Profile.

    Evaluation of Lipid profile parameters

    Measured: Baseline to Week 24

  9. Number of Participants Experiencing Adverse Events After Consuming Saroglitazar Magnesium 2 mg and 4 mg

    Number of Participants with Adverse Events.

    Measured: Baseline to Week 24

  10. Changes in the Glycemic Control and Insulin Resistance; Fasting Plasma Glucose

    Evaluation of Fasting Plasma Glucose

    Measured: Baseline to Week 24

  11. Changes in the Glycemic Control and Insulin Resistance; Hemoglobin A1c

    Evaluation of Hemoglobin A1c

    Measured: Baseline to Week 24

  12. Changes in the Glycemic Control and Insulin Resistance; Insulin

    Evaluation of Insulin

    Measured: Baseline to Week 24

  13. Changes in the Glycemic Control and Insulin Resistance: C-peptide

    Evaluation of C-peptide

    Measured: Baseline to Week 24

  14. Changes in the Glycemic Control and Insulin Resistance: Homeostasis Model Assessment of Beta Cell Function (HOMA -β)

    Evaluation of HOMA of Beta Cell Function Homeostasis model assessment of beta cell function measures as following; HOMA -β = fasting insulin (μU/mL) ×360/{fasting glucose (mg/dL) - 63}.

    HOMA-B provides a quantitative estimate of beta-cell function. A lower HOMA-B value indicates reduced beta-cell function, which can be a sign of progressing towards or already having type 2 diabetes. Conversely, a higher HOMA-B value suggests better beta-cell functionality.

    Measured: Baseline to Week 24

  15. Changes in the Glycemic Control and Insulin Resistance: HOMA of Insulin Resistance

    Evaluation of HOMA of Insulin Resistance Insulin Resistance Index measures insulin resistance, calculated by fasting insulin (μU/mL) multiplied by fasting glucose (mg/dL), and divided by a constant (405). A higher score indicates higher insulin resistance.

    Measured: Baseline to Week 24

  16. Changes in the Glycemic Control and Insulin Resistance: Total Adiponectin

    Evaluation of Total Adiponectin

    Measured: Baseline to Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Mar 2019
  2. Study start12 Jun 2019
  3. Primary completion20 Mar 2020
  4. Study completion20 Mar 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03863574
Sponsor's protocol ID
SARO.17.004
Acronym
EVIDENCES VI
Status last verified
Sep 2024
First submitted
24 Feb 2019
Last updated
15 Oct 2024
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 36731585

  • 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.

    PubMed 33152542

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Saroglitazar Magnesium 2mg and Saroglitazar Magnesium 4mg in people with Non Alcoholic Steatohepatitis, run by Zydus Therapeutics Inc. at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

NAS Score (Nonalcoholic Fatty Liver Disease [NAFLD] Activity Score) (time frame: Baseline to Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03863574, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2024.

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