Clinical trial NCT06427395: Open-Label Extension Study of Saroglitazar Magnesium in Participants With Primary Biliary Cholangitis
Official title: A Multicenter, Open-Label, Extension Clinical Trial to Evaluate Safety and Efficacy of Saroglitazar Magnesium in Participants With Primary Biliary Cholangitis (PBC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Primary Biliary Cholangitis
Keywords: Saroglitazar Magnesium
Primary Biliary Cholangitis
PBC
Lead sponsor: Zydus Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2024-05-23
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Multicenter, Open-Label, phase III, safety and efficacy study
Primary purpose: TREATMENT

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)

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: From baseline to 24 Months/EOT
Secondary outcomes:
measure: Proportion of participants achieving biochemical response based on the composite endpoints of ALP and total bilirubin
timeFrame: From baseline to Months 12 and 24/EOT
measure: Proportion of participants with biochemical response based on the composite endpoints of ALP and total bilirubin
timeFrame: From baseline to Months 12 and 24/EOT
measure: Time to occurrence of the clinical outcome events in study participants with PBC
timeFrame: From baseline to 24 Months/EOT
measure: Time to occurrence of the clinical outcome events based on Model for End Stage Liver Disease 3.0 score
timeFrame: From baseline to 24 Months/EOT
measure: Time to first occurrence of Liver transplant or placement on a liver transplant list
timeFrame: From baseline to 24 Months/EOT
measure: Time to the occurrence of Death
timeFrame: From baseline to 24 Months/EOT
measure: Effect on liver enzyme parameters
timeFrame: From baseline to Months 12 and 24/EOT
measure: Effect on liver enzyme parameters
timeFrame: From baseline to Months 12 and 24/EOT
measure: Effect on liver enzyme parameters
timeFrame: From baseline to Months 12 and 24/EOT
measure: Effect on liver enzyme parameters
timeFrame: From baseline to Months 12 and 24/EOT
measure: Effect on lipid parameters
timeFrame: From baseline to Months 12 and 24/EOT
measure: Effect on lipid parameters
timeFrame: From baseline to Months 12 and 24/EOT
measure: Effect on lipid parameters
timeFrame: From baseline to Months 12 and 24/EOT
measure: Effect on lipid parameters
timeFrame: From baseline to Months 12 and 24/EOT
measure: Effect on lipid parameters
timeFrame: From baseline to Months 12 and 24/EOT
measure: Effect on lipid parameters
timeFrame: From baseline to Months 12 and 24/EOT
measure: Effect on liver enzyme parameters
timeFrame: From baseline to Months 12 and 24/EOT
measure: Effect on disease-related symptoms
timeFrame: From baseline to Months 12 and 24/EOT
measure: Effect on disease-related symptoms
timeFrame: From baseline to Months 12 and 24/EOT
measure: Effect on disease-related symptoms
timeFrame: From baseline to Months 12 and 24/EOT
measure: Effect on liver stiffness measurement (LSM) assessed by Liver elastography/FibroScan
timeFrame: From baseline to Months 12 and 24/EOT
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Zydus US007
state: Alabama
city: Los Angeles
country: United States
facility: Zydus US013
state: California
city: Pasadena
country: United States
facility: Zydus US011
state: California
city: Sacramento
country: United States
facility: Zydus US043
state: California
city: Aurora
country: United States
facility: Zydus US022
state: Colorado
city: New Haven
country: United States
facility: Zydus US037
state: Connecticut
city: Jacksonville
country: United States
facility: Zydus US027
state: Florida
city: Lakewood Ranch
country: United States
facility: Zydus US006
state: Florida
city: Miami
country: United States
facility: Zydus US005
state: Florida
city: Marietta
country: United States
facility: Zydus US020
state: Georgia
city: Indianapolis
country: United States
facility: Zydus US001
state: Indiana
city: Rochester
country: United States
facility: Zydus US035
state: New York
city: Charlotte
country: United States
facility: Zydus US002
state: North Carolina
city: Philadelphia
country: United States
facility: Zydus US015
state: Pennsylvania
city: Houston
country: United States
facility: Zydus US004
state: Texas
city: Houston
country: United States
facility: Zydus US042
state: Texas
city: Murray
country: United States
facility: Zydus US031
state: Utah
city: Charlottesville
country: United States
facility: Zydus US016
state: Virginia
city: Richmond
country: United States
facility: Zydus US039
state: Virginia
city: Seattle
country: United States
facility: Zydus US033
state: Washington
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Zydus AR001
state: Buenos Aires
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Zydus AR007
state: Buenos Aires
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Zydus AR006
state: Buenos Aires
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Zydus AR005
state: Buenos Aires
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Zydus AR003
state: Buenos Aires
city: Pilar
country: Argentina
facility: Zydus AR004
state: Buenos Aires
city: Adana
country: Turkey
facility: Zydus TR014
city: Altındag
country: Turkey
facility: Zydus TR016
city: Ankara
country: Turkey
facility: Zydus TR004
city: Bursa
country: Turkey
facility: Zydus TR005
city: Cebeci
country: Turkey
facility: Zydus TR017
city: Gaziantep
country: Turkey
facility: Zydus TR008
city: Istanbul
country: Turkey
facility: Zydus TR009
city: Istanbul
country: Turkey
facility: Zydus TR010
city: Istanbul
country: Turkey
facility: Zydus TR003
city: Istanbul
country: Turkey
facility: Zydus TR001
city: Izmir
country: Turkey
facility: Zydus TR002
city: Izmir
country: Turkey
facility: Zydus TR013
city: Kocaeli
country: Turkey
facility: Zydus TR011
city: Melikgazi
country: Turkey
facility: Zydus TR015
city: Mersin
country: Turkey
facility: Zydus TR006
Study officials:
affiliation: Zydus Therapeutics Inc.
name: Deven Parmar
role: STUDY_DIRECTOR
References: