Non Alcholic Fatty Liver Disease
Conditions
Brief summary
This is a Phase III, multicentre, randomized, double-blind, placebo-controlled, interventional study designed to evaluate the efficacy and safety of a standardized fraction of Picrorhiza kurroa Royal Ex Benth (Picroliv®) in adults with Non-Alcoholic Fatty Liver Disease (NAFLD). A total of 170 adults aged 18-60 years with uncomplicated NAFLD (fibrosis stage up to F2) will be randomized in a 2:1 ratio to receive either Picroliv 100 mg capsules twice daily or matching placebo, in addition to standard of care, for a treatment duration of 24 weeks. Standard of care includes dietary and lifestyle modifications, exercise recommendations, and management of comorbid conditions as per routine clinical practice. The study aims to assess the efficacy of Picroliv in improving hepatic and metabolic parameters and to evaluate its safety profile compared with placebo. Participants will be followed for a total study duration of 48 weeks. The trial will be conducted across six clinical sites in India.
Detailed description
Non-Alcoholic Fatty Liver Disease (NAFLD) is a highly prevalent metabolic liver disorder with limited pharmacological treatment options. Lifestyle modification remains the mainstay of management, highlighting the need for safe and effective therapeutic agents. Picroliv®, a standardized ethanolic extract of the roots and rhizomes of Picrorhiza kurroa, has demonstrated hepatoprotective, antioxidant, and anti-inflammatory properties in preclinical studies and early clinical investigations. This Phase III, multicentre, randomized, double-blind, placebo-controlled, two-arm interventional study is designed to evaluate the efficacy and safety of Picroliv in adults diagnosed with uncomplicated NAFLD (fibrosis stage up to F2). Eligible participants aged 18-60 years will be randomized in a 2:1 ratio to receive either Picroliv 100 mg capsules twice daily or matching placebo, in addition to standard of care, for 24 weeks. Standard of care includes dietary counseling, exercise recommendations, and management of associated comorbidities as per routine clinical practice. Participants will be followed for a total study duration of 48 weeks. The study will be conducted at six clinical centers in India.
Interventions
DRUGPicroliv
Participants will receive Picroliv 100 mg capsules twice daily (after meals) for 24 weeks, in addition to standard of care, which includes dietary counseling, exercise recommendations, and management of comorbid conditions as per routine clinical practice.
OTHERPlacebo
Participants will receive matching placebo capsules twice daily (after meals) for 24 weeks, in addition to standard of care, which includes dietary counseling, exercise recommendations, and management of comorbid conditions as per routine clinical practice.
Sponsors
Bioagile Therapeutics Pvt. Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Age: 18- 60 years 2. Sex: Both males and females 3. Patients showing presence of hepatic fat fraction as defined by ≥ 10% on MRI-PDFF at screening. 4. Liver enzymes normal or above the ULN (upper limit of normal range) but less than 3 times 5. Hemoglobin ≥10 g/dL, a platelet count ≥ 100 x 109/L, and a white blood cell count ≥ 3.0 x 109/L 6. HbA1c \< 7% (if participant has Type 2 diabetes mellitus (T2DM) should be controlled with appropriate treatment for the same except thiazolidinediones) 7. TSH within normal limits (WNL) at screening 8. If on metformin, sulfonylureas, statins, or fibrates, subjects must be on a stable dose of these drugs for at least three months prior to Screening and during the study will be allowed if on stable doses in the preceding 12 weeks and will be continued throughout the study.
Exclusion criteria
1. Significant alcohol consumption (\> 210 g/week in males and \> 70 g/week in females) 2. eGFR \< 60 mL/min / 1.73m2 or patients on dialysis 3. Hepato-biliary disorders: Cirrhosis, biliary obstruction, chronic cholecystitis, cholelithiasis, active or chronic active Hepatitis B or hepatitis C, autoimmune liver diseases 4. Medical conditions including stroke, Alzheimer's disease, tuberculosis, Ischemic Heart Disease (IHD), Deep Vein Thrombosis (DVT), pancreatitis, inflammatory rheumatic diseases, cancer or any disorder that may potentially impact the outcome measures 5. Patients on drugs potentially associated with NAFLD such as amiodarone, methotrexate, perhexiline, estrogens, tamoxifen, nifedipine, diltiazem, chloroquine and other hepatotoxic agents as per the discretion of the study investigator. 6. Medications for disease conditions (e.g., HIV-1, HBV, or HCV infection, active cancer, transplantation are also excluded from the study. 7. Subjects on anti TNF therapies, other biologicals and probiotics 8. Subjects on Thiazolidinediones (TZDs), Saroglitazar, Atazanavir, Indinavir, Ketoconazole, Valproic acid, Silybum marianum, Valeriana officinalis and hepatoprotective plants / Traditional medicine formulations / natural products. 9. Subjects on medications that may affect glucose metabolism such as corticosteroids, opiates, barbiturates and anticoagulants. 10. Any disorder or clinically significant finding that may potentially impact the outcome measures as per the discretion of the study investigator. 11. Pregnant and lactating women. 12. Patients with a history of serious drug allergies (such as anaphylactic shock) 13. Not willing to provide written informed consent 14. Females unwilling to use any form of contraception during the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in hepatic fat fraction | Baseline to Week 24 | Measured as the change from baseline in hepatic fat fraction (%) assessed by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) at Week 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in liver stiffness | Baseline to Week 24 | Change from baseline in liver stiffness measurement assessed by transient elastography at Week 24. |
| Change in Serum Alanine Aminotransferase (ALT) | Baseline to Week 24 | Change from baseline in serum alanine aminotransferase (ALT) levels to Week 24, and comparison of the mean change between treatment groups. |
| Change in Fasting Plasma Glucose | Baseline to Week 24 | Change from baseline in fasting plasma glucose levels at Week 24 and comparison of the mean change between treatment groups. |
| Change in fibrosis score | Baseline to Week 24 | Change from baseline in liver fibrosis assessed by transient elastography (FibroScan®) at Week 24. Transient elastography measures liver stiffness in kilopascals (kPa), which reflects the degree of liver fibrosis. Liver stiffness values typically range from \~2 to 75 kPa, with higher values indicating greater liver stiffness and more severe fibrosis. |
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | Baseline to Week 48 | Number and percentage of participants experiencing at least one treatment-emergent adverse event (TEAE) during the study period. |
| Change in Serum Aspartate Aminotransferase (AST) | Baseline to Week 24 | Change from baseline in serum aspartate aminotransferase (AST) levels to Week 24, and comparison of the mean change between treatment groups. |
| Change in Glycated Hemoglobin (HbA1c) | Baseline to Week 24 | Change from baseline in glycated hemoglobin (HbA1c) levels at Week 24 and comparison of the mean change between treatment groups. |
| Change in Total Cholesterol | Baseline to Week 24 | Change from baseline in total cholesterol levels at Week 24 and comparison of the mean change between treatment groups. |
| Change in Low-Density Lipoprotein Cholesterol (LDL-C) | Baseline to Week 24 | Change from baseline in LDL-C levels at Week 24 and comparison of the mean change between treatment groups. |
| Change in High-Density Lipoprotein Cholesterol (HDL-C) | Baseline to Week 24 | Change from baseline in HDL-C levels at Week 24 and comparison of the mean change between treatment groups. |
| Change in Triglycerides | Baseline to Week 24 | Change from baseline in triglyceride levels at Week 24 and comparison of the mean change between treatment groups. |
| Severity of Treatment-Emergent Adverse Events (TEAEs) | Baseline to Week 48 | Severity of treatment-emergent adverse events (TEAEs) will be assessed and graded using the Common Terminology Criteria for Adverse Events (CTCAE) developed by the U.S. National Cancer Institute. The CTCAE grading system ranges from Grade 1 to Grade 5, where Grade 1 = Mild adverse event, Grade 2 = Moderate adverse event, Grade 3 = Severe adverse event, Grade 4 = Life-threatening or disabling adverse event, and Grade 5 = Death related to the adverse event. Higher grades indicate greater severity and worse clinical outcomes. |
Countries
India
Contacts
STUDY_DIRECTORDr Vivek Bhosale
CDRI
Outcome results
None listed