Saroglitazar Magnesium 4 mg for NASH in People Living With HIV in the US (SARONAPLUS)

S
Samer Gawrieh, MD

Primary Investigator

Administratively Closed
18 years or above
All
Phase 2
160 participants needed
3 Locations

Brief description of study

Saroglitazar Magnesium 4 mg for NASH in People Living with HIV in the US

Detailed description of study

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial of Saroglitazar Magnesiumhe Treatment of Nonalcoholic Steatohepatitis (NASH) in People Living with Humanunodeficiency Virus (HIV) in the US

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Nonalcoholic Steatohepatitis
  • Age: 18 years or above
  • Gender: All

Inclusion Criteria:
  1. Adults (≥18 years of age) with documented HIV.
  2. Histologic confirmation of NASH from liver biopsy within 6 months prior to screeningd clinical biopsy in patients with suspected NASH pending confirmation ofver biopsy criteria including a NAS ≥4 (with at least one-point each for steatosis,bular inflammation, and ballooning).
  3. HIV-1 RNA <50 copies/mL for ≥6 months on ART (must have screening HIV-1 RNA value andvalue within 6 months prior to screening and up to the randomizationhat meets the criteria).
  4. Stable ART regimen for ≥3 months prior to screening and stable up to the randomizationd no active plans to change ART while on study.
  5. Willingness to participate in the study and undergo an EOT liver biopsy
Exclusion Criteria:
  1. History of significant alcohol consumption (defined as >2 drinks/day on average for>1 drinks/day on average for women) for at least 3 consecutive months (12utive weeks) within 5 year before screening (Note 1: 1 drink =12 ounces of beer,8-9 ounces of malt liquor, 4 ounces of wine or 1 ounce of spirits/hard liquor. Note 2:gned at birth for alcohol consumption limits).
  2. History of other acute or chronic liver disease, including, but not limited toutoimmune, primary biliary cholangitis, Wilson's disease, alpha 1 antitrypsindeficiency, hemochromatosis, hepatitis B virus (HBV), and ongoing or recent (withinhe past 3 years) hepatitis C RNA positivity. (Exceptions: a. Participants withviously treated hepatitis C infection are eligible for consideration if theirustained virologic response was achieved more than 3 years prior to screening. Theuch participants in this trial will not exceed 25% of the study cohort.
  3. Participants with prior acute HBV infection that is resolved but currently do nothave hepatitis B surface antigen (HBsAg) or detectable HBV Deoxyribonucleic acid (HBVDNA) are eligible).
  4. History of liver transplant.
  5. Liver biopsy or radiologic imaging consistent with the clinical presence of cirrhosishypertension at screening.
  6. Participants whose Visit 2 ALT, AST, or alkaline phosphatase (ALP) values exceed theirVisit 1 values by more than 50%. Note: These participants will be required to have ahird value measured to assess for a trend. If the third value shows a continued≥10% compared to the Visit 2 values, the participant is considered ineligibledomization.
  7. Ongoing use of steatogenic medications or supra-physiologic hormonal therapies(exception: transgender women on stable dose [for ≥3 months] of feminizing hormonalherapy), within 3 months prior to screening or historical liver biopsy until time ofdomization or anticipated use of medications that cause significant changes inweight during the study period; (Refer Appendix 7 for 'List of Medications').
  8. Uncontrolled type 2 diabetes mellitus, defined as HbA1c >9.5% at screening.
  9. Any of the following laboratory values at screening:
    1. ALT or AST >250 U/L.
    2. Total bilirubin >1.5 mg/dL and direct bilirubin > 0.5 mg/dL (unless due toGilbert's disease or atazanavir use per the opinion of the site investigator).
    3. Platelet count <150,000/mm3.
    4. Estimated glomerular filtration rate (e-GFR) <60 mL/min/1.73m2 using the chronickidney disease-epidemiology collaboration (CKD-EPI) equation (Refer Appendix 6CKD-EPI Calculator').
    5. International normalized ratio (INR) >1.3.
    6. Albumin < 3.6 g/dL
  10. History of malignancy in the past 5 years and/or active neoplasm with the exception of
    superficial, non-melanoma, skin cancer.
  11. Participants with child-bearing potential (pregnancy or inability or unwilling tohe study duration) or breast-feeding.
  12. Unstable cardiovascular disease, including:
    1. Unstable angina, (i.e., new or worsening symptoms of coronary heart disease)d/or acute myocardial infarction within the 3 months preceding screening
    2. Acute coronary syndrome or coronary artery intervention, within the 6 monthsding screening
    3. Heart failure of New York Heart Association (NYHA) class (III-IV) or worseninggestive heart failure within the 6 months preceding screening.
    4. History of (within 3 months preceding screening) or current unstable cardiacdysrhythmias.
    5. Uncontrolled hypertension (systolic blood pressure [SBP] >155 mm Hg and/ordiastolic blood pressure [DBP] >95 mm Hg) at screening.
    6. Stroke or transient ischemic attack within the 6 months preceding screening.
  13. Unstable pulmonary disease (based upon site investigator's evaluation) at screening.
  14. Use of drugs that are known CYP2C8 inhibitors/substrates (Refer Appendix 2 for theList of Known CYP2C8 inhibitors/substrates') in the last 28 days preceding screening.
  15. History of severe illness or any other conditions (such as poorly controlledychiatric disease, active gastrointestinal conditions that might interfere with drugbsorption, etc.) that require systemic treatment/or hospitalization, untilher completes therapy or is clinically stable on therapy as per thehe site investigator, for at least 7 days prior to screening.
  16. Use of other PPAR agonists (fibrates, thiazolidinediones, telmisartan) within 6 monthsg or historical liver biopsy until time of randomization.
  17. Use of unstable doses of sodium-glucose cotransporter-2 (SGLT2) inhibitors (e.g.gliflozin, empagliflozin, dapagliflozin, etc.) or glucagon-like peptide (GLP)-1gonists (e.g. exenatide, liraglutide, lixisenatide, etc.) within 6 months prior tog or historical liver biopsy until time of randomization.
  18. Use of pentoxifylline, ursodeoxycholic acid, antioxidants such as vitamin E (>200/day), glutathione, orlistat, betaine, incretin mimetics or non-prescribedy alternative medications within 6 months prior to screening or historicalver biopsy until time of randomization.
  19. Known allergy, sensitivity or intolerance to the study medication or formulationgredients.
  20. History of any known bleeding disorder or coagulopathy.
  21. Any condition that in the opinion of the site investigator, would compromise thebility to participate in the study.
  22. Unstable doses of anti-diabetic agents, including sulfonylureas, biguanides ordipeptidyl peptidase-4 (DPP-4) inhibitors in the last 3 months prior to screening orhistorical liver biopsy until time of randomization.
  23. Unstable doses of lipid-lowering agents such as statins (e.g. simvastatin,vastatin, atorvastatin, fluvastatin, lovastatin, rosuvastatin, etc.) in the last 3hs prior to screening or historical liver biopsy until time of randomization.
  24. Participant with weight change >5% within 6 months prior to screening or historicalver biopsy until time of randomization.
  25. History of bariatric surgery or currently undergoing evaluation for bariatric surgery.
  26. Participation in another interventional clinical study and/or receipt of any othervestigational medication within 3 months prior to screening or historical liverbiopsy .
  27. History of COVID-19 infection in the last 30 days prior to screening.
  28. Pregnancy-related exclusions, including:
    1. Pregnant/lactating female (including positive pregnancy test at screening)
    2. Fertile women participants and their male counterparts or vice versa, not usingve contraceptive methods (such as an intra-uterine contraceptive device,her mechanical contraceptive methods like use of condom and diaphragm alongwith spermicide, or hormonal contraceptives that inhibit ovulation) throughouthe study.
(Note: Enrolled females otherwise must be surgically sterilized for at least 24 weeks before screening; postmenopausal, defined as 52 weeks with no menses without an alternative medical cause; or following sexual abstinence).

Updated on 13 Dec 2024. Study ID: SARO.20.001, GI-ZYDUS-SARONAPLUS, 15610

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