Saroglitazar Magnesium for Nonalcoholic Fatty Liver Disease with Fibrosis

(NASH Trial)

Not currently recruiting at 154 trial locations

Overseen By Farheen Shaikh

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Zydus Therapeutics Inc.

Must not be taking: Anti-NASH, Antidiabetics, Immune modulators, others

Disqualifiers: Alcohol use, Liver diseases, Cirrhosis, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, Saroglitazar Magnesium, for individuals with nonalcoholic fatty liver disease, specifically nonalcoholic steatohepatitis (NASH) with liver fibrosis (scarring). The goal is to determine if this treatment can improve liver health. Participants will receive either Saroglitazar Magnesium or a placebo (a pill with no active drug) to compare effectiveness. Suitable candidates have been diagnosed with NASH and liver fibrosis and maintain a stable body weight. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial requires that certain medications be stopped or stabilized before participation. If you're on anti-diabetic medications, they must be stable for at least 90 days before screening. Some medications, like those affecting liver conditions or weight loss, need to be stopped 28 to 120 days before screening, depending on the type. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Saroglitazar Magnesium is generally safe for patients. Studies indicate that this treatment is well-tolerated by individuals with nonalcoholic fatty liver disease (NAFLD) and similar conditions.

One study found that patients did not experience severe side effects, and the treatment was mostly safe. Another analysis demonstrated improvements in liver health without major problems. No serious concerns about liver damage or other critical issues have been reported.

As this is a Phase 2 trial, some evidence already suggests the treatment is safe for humans, but researchers continue to gather more information. Overall, Saroglitazar Magnesium has maintained a good safety record in studies so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Saroglitazar Magnesium for treating nonalcoholic fatty liver disease (NAFLD) with fibrosis because it offers a novel approach compared to existing treatments. Unlike standard treatments, which often focus on lifestyle changes and controlling blood sugar and cholesterol levels, Saroglitazar Magnesium acts as a dual PPAR (peroxisome proliferator-activated receptor) agonist. This means it targets both PPAR-alpha and PPAR-gamma pathways, potentially reducing liver inflammation and fibrosis more effectively. Additionally, it is administered as a simple oral tablet, making it convenient for patients to take daily. This dual-action mechanism and ease of use make Saroglitazar Magnesium a promising candidate for improving liver health in patients with NAFLD.

What evidence suggests that Saroglitazar Magnesium might be an effective treatment for Nonalcoholic Steatohepatitis?

Studies have shown that Saroglitazar Magnesium can be effective for nonalcoholic fatty liver disease, especially when liver scarring (fibrosis) is present. Research indicates that a 4 mg dose of Saroglitazar improves liver enzymes and reduces liver stiffness, key indicators of liver health. In this trial, participants will receive either a 2 mg or 4 mg dose of Saroglitazar Magnesium, or a placebo. Patients have also experienced improvements in metabolic factors, such as blood sugar and cholesterol levels. Additionally, Saroglitazar has been linked to better control of these factors, which are important for overall health. Overall, these findings suggest that Saroglitazar Magnesium may be a promising treatment for improving liver health in people with nonalcoholic steatohepatitis (NASH). ^{2 4 6 7 8}

Who Is on the Research Team?

Deven V. Parmar, MD, FCP

Principal Investigator

Zydus Therapeutics Inc.

Are You a Good Fit for This Trial?

Adults aged 18-75 with a BMI ≤45 kg/m² and moderate type 2 diabetes (if applicable) can join this trial. They must have nonalcoholic steatohepatitis (NASH) with fibrosis confirmed by biopsy, not be significantly overweight or underweight, and agree to follow the study rules. People with unstable heart conditions, recent strokes, certain muscle diseases, severe liver issues like cirrhosis or cancer within the last five years cannot participate.

Inclusion Criteria

Your weight should not have changed more than 5% between the time of your biopsy and when you start the study.

My liver biopsy confirms NASH with significant fibrosis and a NAS score of 5 or more.

I have been taking the same dose of vitamin E (>400 IU/day) for at least 24 weeks.

Exclusion Criteria

I have been diagnosed with cirrhosis within the last 24 weeks.

I have been on stable diabetes medication for at least 90 days.

Use of concurrent medications prior to screening including: Anti-NASH therapy(s) including S-adenosyl methionine (SAMe), ursodeoxycholic acid (UDCA), obeticholic acid and milk thistle in the period from 90 days prior to screening or, if a historical biopsy is used, from 90 days prior to baseline liver biopsy until time of screening, Antidiabetic mediation which may impact NASH histology including thiazolidinediones (pioglitazone, rosiglitazone) in the period from 90 days prior to screening or, if a historical biopsy is used, from 90 days prior to baseline liver biopsy until time of screening, Immune modulatory agents including anti-TNF-α therapies (infliximab, adalimumab, etanercept) or anti-integrin therapy (namixilab) in the period from 28 days prior to screening or if a historical biopsy is used from 28 days prior to baseline liver biopsy until time of screening, Any treatment or anticipated initiation (intended use for more than 14 consecutive days) of medications known to have an effect on steatosis (e.g. treatment with corticosteroids [topical and inhaled are allowed]), methotrexate, tamoxifen, valproic acid, amiodarone or tetracycline, estrogens in doses higher than used in oral contraceptives, vitamin A, L-asparaginase, valproate, chloroquine, or antiretroviral drugs in the period from 28 days prior to screening or, if a historical biopsy is used, from 28 days prior to baseline liver biopsy until time of screening, Treatment with orlistat, zonisamide, topiramate, phentermine, lorcaserin, bupropion, or naltrexone alone, or in combination or any other medication, that could promote weight loss, in the opinion of the investigator, in the period from 28 days prior to screening or if a historical biopsy is used from 28 days prior to baseline liver biopsy until time of screening, Changing doses of statins (simvastatin, pitavastatin, pravastatin, atorvastatin, fluvastatin, lovastatin, rosuvastatin) or fibrates (clofibrate, Fenofibrate) in the 90 days preceding screening, Use of drugs that are known CYP2C8 inhibitors/substrate in the 28 days preceding screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Saroglitazar Magnesium or placebo once daily for the duration of the treatment

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Saroglitazar Magnesium

Trial Overview The trial is testing Saroglitazar Magnesium at two different doses (4 mg and 2 mg) against a placebo to treat NASH with fibrosis. Participants will randomly receive one of these treatments to see how effective they are in improving their liver health compared to no active treatment.

How Is the Trial Designed?

Group I: Saroglitazar Magnesium 4 mg Experimental Treatment 1 Intervention

Saroglitazar Magnesium 4 mg tablet orally administered once daily in the morning before breakfast without food, for the duration of treatment.

Group II: Saroglitazar Magnesium 2 mg Experimental Treatment 1 Intervention

Saroglitazar Magnesium 2 mg tablet orally administered once daily in the morning before breakfast without food, for the duration of treatment.

Group III: Placebo Placebo Group 1 Intervention

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

Saroglitazar Magnesium is already approved in India for the following indications:

Approved in India as Lipaglyn for:

• Type 2 diabetes mellitus
• Dyslipidemia
• Non-alcoholic fatty liver disease (NAFLD)
• Non-alcoholic steatohepatitis (NASH)

Who Is Running the Clinical Trial?

Zydus Therapeutics Inc.

Lead Sponsor

Trials

16

Recruited

1,100+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9077151/

Saroglitazar for Nonalcoholic Fatty Liver Disease: A Single ... This oral drug is now widely used in India for the treatment of NASH. Although weight reduction and saroglitazar have shown to be effective in NAFLD, there is ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2210740123000992

Effects of saroglitazar in the treatment of non-alcoholic fatty ... Treatment with adjunct 4 mg saroglitazar could significantly improve liver enzymes, reduce liver stiffness, and improve metabolic parameters.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12395119/

Evaluation of Effectiveness and Tolerability of Saroglitazar in ... Furthermore, a clinical case series enumerated the significant benefits of saroglitazar in considerably improving glycemic control, lipid ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03061721?intr=Saroglitazar%20&viewType=Table&rank=7

Study Details | NCT03061721 | Saroglitazar Magnesium in ... Changes in enhanced liver fibrosis in Saroglitazar Magnesium groups as compared to the placebo group The ELF Score is a liver fibrosis score that is calculated ...

5. nature.com nature.com/articles/s41598-020-78342-x

Saroglitazar in patients with non-alcoholic fatty liver ... We conclude that Saroglitazar leads to significant improvement in transaminases, LSM, and CAP in NAFLD patients with DD.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10037031/

Efficacy and safety of saroglitazar in real‐world patients ... Saroglitazar, a dual PPAR α/γ agonist, is useful in management of NAFLD and diabetic dyslipidemia. Here, we report the safety and efficacy of saroglitazar ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05211284

Saroglitazar Magnesium 4 mg for Nonalcoholic Fatty Liver ... A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial of Saroglitazar Magnesium for the Treatment of Nonalcoholic Fatty Liver Disease (NAFLD) in ...

8. journals.lww.com journals.lww.com/ajg/fulltext/2023/10001/s1430_saroglitazar_improves_metabolic_profile,.2391.aspx

S1430 Saroglitazar Improves Metabolic Profile, Hepatic... This systematic review evaluated the efficacy of oral Saroglitazar 4 mg in improving metabolic profile, hepatic steatosis, inflammation and fibrosis in patients ...