Primary Biliary Cholangitis
Conditions
Keywords
Saroglitazar Magnesium, Primary Biliary Cholangitis, PBC
Brief summary
Open-Label Extension Study of Saroglitazar Magnesium in Participants With Primary Biliary Cholangitis
Detailed description
A Multicenter, Open-Label, Extension Clinical trial to evaluate Safety and Efficacy of Saroglitazar Magnesium in Participants with Primary Biliary Cholangitis (PBC)
Interventions
Saroglitazar Magnesium 1 mg will be assigned to all participants enrolled in the open label extension program
Sponsors
Zydus Therapeutics Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Multicenter, Open-Label, phase III, safety and efficacy study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Must provide written informed consent and agree to comply with the trial protocol 2. Participated and completed SARO.21.001, the double-blind treatment phase study
Exclusion criteria
1. Consumption of 2 standard drinks per day if male and 1 standard drink per day if female for 3 consecutive months (12 consecutive weeks) throughout double-blind phase till screening. 2. Participants with MELD 3.0 score of 15 or greater 3. History or presence of other concomitant liver diseases at screening: 1. Chronic hepatitis B or C virus (HBV, HCV) infection 2. Primary sclerosing cholangitis (PSC) 3. Alcoholic liver disease 4. Autoimmune hepatitis (AIH)-PBC overlap syndrome 5. Hemochromatosis 6. Non-alcoholic steatohepatitis (NASH) on historical biopsy 4. Cirrhosis with complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma, uncontrolled ascites, encephalopathy, history of variceal bleeding or history of hepatorenal syndrome at screening. 5. Use of Thiazolidinediones or Fibrates (within 12 weeks prior to screening) 6. Use of other PPAR agonists (i.e., Elafibranor, Seladelpar), Obeticholic acid (OCA), methotrexate, budesonide and other systemic corticosteroids (Prednisone dose more than 10 mg); potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazid, or nitrofurantoin) (within 12 weeks prior to screening) 7. History of bowel surgery (gastrointestinal \[bariatric\] surgery in the preceding 1 year or undergoing evaluation for gastrointestinal surgery (bariatric surgery for obesity, extensive small-bowel resection) or orthotopic liver transplant (OLT) or listed for OLT 8. Unstable cardiovascular disease, including: 1. Unstable angina, (i.e., new or worsening symptoms of coronary heart disease in the 12 weeks before screening and throughout the screening period), acute coronary syndrome in the 24 weeks before screening and throughout the screening period, acute myocardial infarction in the 12 weeks before screening and throughout the screening period or heart failure of New York Heart Association class (III - IV) or worsening congestive heart failure, or coronary artery intervention, in the 24 weeks before screening and throughout the screening period 2. History/current unstable cardiac dysrhythmias 3. Uncontrolled hypertension at screening 4. Stroke or transient ischemic attack in the 24 weeks before screening 9. History of intracranial hemorrhage, arteriovenous malformation, bleeding disorder, and coagulation disorders 10. An uncontrolled thyroid disorder 1. Uncontrolled hyperthyroidism: defined as any history of hyperthyroidism that has either not been treated with either radioactive iodine and/or surgery or that has been treated with radioactive iodine and/or surgery, but has required ongoing continuous or intermittent use of thyroid hormone synthesis inhibitors (i.e., methimazole or propylthiouracil) in the 24 weeks before screening 2. Uncontrolled hypothyroidism: defined as initiation of thyroid hormone replacement therapy or dose adjustment of replacement therapy in the 12 weeks before screening 11. History of myopathies or evidence of active muscle disease demonstrated by CPK ≥ 5 × ULN at screening 12. Any of the following laboratory values: 1. Total bilirubin \> 3 x ULN 2. Platelets \< 50 × 103/mL 3. Albumin \< 2.8 g/dL 4. eGFR \< 45 mL/min/1.73 m2 5. ALT or AST \> 250 U/L 6. ALP \> 10 × ULN 13. Participation in another interventional clinical study and receipt of any other investigational medication or medical device within 30 days or within 5 half-lives, whatever is longer, prior to screening 14. History of malignancy in the past 5 years and/or active neoplasm which may diminish life expectancy (except resolved superficial non-melanoma skin cancer, carcinomas in situ or other stable, relatively benign conditions if appropriately treated prior to screening) 15. Known allergy, sensitivity or intolerance to the study medication or formulation ingredients 16. Pregnancy-related exclusions, including: 1. Pregnant/lactating female (including positive pregnancy test at screening) 2. Participants agree to avoid pregnancy either by true abstinence or the use of an acceptable effective contraceptive measures for the duration of the study and for at least 1 month after the end of the study medication. Refer Appendix 9 Contraceptive Guidance. 17. History or other evidence of severe illness or any other conditions that would make the participant, in the opinion of the investigator, unsuitable for the study (such as poorly controlled psychiatric disease, HIV, coronary artery disease or active gastrointestinal conditions that might interfere with drug absorption) 18. Cirrhosis with Child-Pugh-Turcotte (CPT) class B or C having score of 7 or above at screening (Refer Appendix 11
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | From baseline to 24 Months/EOT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving biochemical response based on the composite endpoints of ALP and total bilirubin | From baseline to Months 12 and 24/EOT | ALP \< 1.67 x ULN, ≥ 15% decrease in ALP, and total bilirubin ≤ ULN or direct bilirubin ≤ ULN relative to baseline in participants with known Gilbert's syndrome |
| Proportion of participants with biochemical response based on the composite endpoints of ALP and total bilirubin | From baseline to Months 12 and 24/EOT | complete normalization of ALP. Change and percent change from baseline in ALP |
| Time to occurrence of the clinical outcome events in study participants with PBC | From baseline to 24 Months/EOT | Defined as new onset or recurrence of any of the following: * Hospitalization for new onset or recurrence of variceal bleed * Hepatic encephalopathy (as defined by a West Haven score ≥2) * New onset ascites requiring treatment * Refractory ascites (requiring large volume paracentesis) * Spontaneous bacterial peritonitis (confirmed by culture from diagnostic paracentesis) |
| Time to occurrence of the clinical outcome events based on Model for End Stage Liver Disease 3.0 score | From baseline to 24 Months/EOT | Time from enrolment to the first occurrence of Model for End Stage Liver Disease 3.0 score ≥ 15 and 25% increase from baseline as measured on 2 consecutive occasions performed at least two weeks apart with no competing etiologies identified |
| Time to first occurrence of Liver transplant or placement on a liver transplant list | From baseline to 24 Months/EOT | — |
| Time to the occurrence of Death | From baseline to 24 Months/EOT | Death (liver and non-liver related) |
| Effect on liver enzyme parameters | From baseline to Months 12 and 24/EOT | Change from baseline in ALT |
| Effect on lipid parameters | From baseline to Months 12 and 24/EOT | Change from baseline in TG |
| Effect on disease-related symptoms | From baseline to Months 12 and 24/EOT | Change from baseline in quality of life (Primary Biliary Cholangitis- 40) questionnaire domains Scale as Never, Rarely, Sometimes, Most of the time, and Always |
| Effect on liver stiffness measurement (LSM) assessed by Liver elastography/FibroScan | From baseline to Months 12 and 24/EOT | Change from baseline in LSM assessed by Liver elastography/FibroScan |
Countries
Argentina, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORDeven Parmar
Zydus Therapeutics Inc.
Outcome results
None listed