Open-Label Extension Study of Saroglitazar Magnesium in Participants With Primary Biliary Cholangitis

Primary Biliary Cholangitis Clinical Trial

Official title:

A Multicenter, Open-Label, Extension Clinical Trial to Evaluate Safety and Efficacy of Saroglitazar Magnesium in Participants With Primary Biliary Cholangitis (PBC)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06427395
• Other study ID #: SARO.23.002
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 15, 2024
• Est. completion date: July 18, 2027

Study information

• Verified date: May 2024
• Source: Zydus Therapeutics Inc.
• Contact: Farheen Shaikh
• Phone: 609-730-1900
• Email: fshaikh[@]zydustherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Open-Label Extension Study of Saroglitazar Magnesium in Participants With Primary Biliary Cholangitis

Description:

A Multicenter, Open-Label, Extension Clinical trial to evaluate Safety and Efficacy of Saroglitazar Magnesium in Participants with Primary Biliary Cholangitis (PBC)

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 150
• Est. completion date: July 18, 2027
• Est. primary completion date: April 18, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 Obeticholic acid (OCA), methotrexate, budesonide and other systemic corticosteroids (Prednisone dose more than 10 mg); potentially hepatotoxic drugs (including a-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 x ULN

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

Related Conditions & MeSH terms

• Cholangitis
• Liver Cirrhosis, Biliary
• Primary Biliary Cholangitis

Intervention

Drug:
• Saroglitazar Magnesium 1 mg
Saroglitazar Magnesium 1 mg will be assigned to all participants enrolled in the open label extension program

Locations

Country	Name	City	State
Argentina	Zydus AR001	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	Zydus AR003	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	Zydus AR005	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	Zydus AR006	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	Zydus AR007	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	Zydus AR009	Mar del Plata	Buenos Aires
Argentina	Zydus AR004	Pilar	Buenos Aires
Argentina	Zydus AR010	Rosario	Santa Fe
Turkey	Zydus TR014	Adana
Turkey	Zydus TR016	Altindag
Turkey	Zydus TR004	Ankara
Turkey	Zydus TR005	Bursa
Turkey	Zydus TR017	Cebeci
Turkey	Zydus TR008	Gaziantep
Turkey	Zydus TR001	Istanbul
Turkey	Zydus TR003	Istanbul
Turkey	Zydus TR009	Istanbul
Turkey	Zydus TR010	Istanbul
Turkey	Zydus TR002	Izmir
Turkey	Zydus TR013	Izmir
Turkey	Zydus TR011	Kocaeli
Turkey	Zydus TR015	Melikgazi
Turkey	Zydus TR006	Mersin
United States	Zydus US022	Aurora	Colorado
United States	Zydus US007	Birmingham	Alabama
United States	Zydus US002	Charlotte	North Carolina
United States	Zydus US016	Charlottesville	Virginia
United States	Zydus US014	Cincinnati	Ohio
United States	Zydus US004	Houston	Texas
United States	Zydus US042	Houston	Texas
United States	Zydus US001	Indianapolis	Indiana
United States	Zydus US027	Jacksonville	Florida
United States	Zydus US006	Lakewood Ranch	Florida
United States	Zydus US013	Los Angeles	California
United States	Zydus US020	Marietta	Georgia
United States	Zydus US005	Miami	Florida
United States	Zydus US031	Murray	Utah
United States	Zydus US037	New Haven	Connecticut
United States	Zydus US024	Omaha	Nebraska
United States	Zydus US011	Pasadena	California
United States	Zydus US015	Philadelphia	Pennsylvania
United States	Zydus US039	Richmond	Virginia
United States	Zydus US023	Rochester	Minnesota
United States	Zydus US035	Rochester	New York
United States	Zydus US043	Sacramento	California
United States	Zydus US030	Saint Louis	Missouri
United States	Zydus US033	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Zydus Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0		From baseline to 24 Months/EOT
Secondary	Proportion of participants achieving biochemical response based on the composite endpoints of ALP and total bilirubin	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	From baseline to Months 12 and 24/EOT
Secondary	Proportion of participants with biochemical response based on the composite endpoints of ALP and total bilirubin	complete normalization of ALP. Change and percent change from baseline in ALP	From baseline to Months 12 and 24/EOT
Secondary	Time to occurrence of the clinical outcome events in study participants with PBC	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)	From baseline to 24 Months/EOT
Secondary	Time to occurrence of the clinical outcome events based on Model for End Stage Liver Disease 3.0 score	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	From baseline to 24 Months/EOT
Secondary	Time to first occurrence of Liver transplant or placement on a liver transplant list		From baseline to 24 Months/EOT
Secondary	Time to the occurrence of Death	Death (liver and non-liver related)	From baseline to 24 Months/EOT
Secondary	Effect on liver enzyme parameters	Change from baseline in ALT	From baseline to Months 12 and 24/EOT
Secondary	Effect on liver enzyme parameters	Change from baseline in AST	From baseline to Months 12 and 24/EOT
Secondary	Effect on liver enzyme parameters	Change from baseline in GGT	From baseline to Months 12 and 24/EOT
Secondary	Effect on liver enzyme parameters	Change from baseline in total bilirubin	From baseline to Months 12 and 24/EOT
Secondary	Effect on lipid parameters	Change from baseline in TG	From baseline to Months 12 and 24/EOT
Secondary	Effect on lipid parameters	Change from baseline in LDL-C	From baseline to Months 12 and 24/EOT
Secondary	Effect on lipid parameters	Change from baseline in HDL-C	From baseline to Months 12 and 24/EOT
Secondary	Effect on lipid parameters	Change from baseline in VLDL-C	From baseline to Months 12 and 24/EOT
Secondary	Effect on lipid parameters	Change from baseline in total cholesterol	From baseline to Months 12 and 24/EOT
Secondary	Effect on lipid parameters	Change from baseline in non-HDL-C	From baseline to Months 12 and 24/EOT
Secondary	Effect on liver enzyme parameters	Change from baseline in serum bile acids	From baseline to Months 12 and 24/EOT
Secondary	Effect on disease-related symptoms	Change from baseline in quality of life (Primary Biliary Cholangitis- 40) questionnaire domains Scale as Never, Rarely, Sometimes, Most of the time, and Always	From baseline to Months 12 and 24/EOT
Secondary	Effect on disease-related symptoms	Change from baseline in 5-D itch scale Score ranging from 5 to 25, where higher score represents worst itching	From baseline to Months 12 and 24/EOT
Secondary	Effect on disease-related symptoms	Change from baseline in Worst Itch NRS (numerical rating scale) scores 0-10, where 0 is no itch and 10 is worst itch imaginable	From baseline to Months 12 and 24/EOT
Secondary	Effect on liver stiffness measurement (LSM) assessed by Liver elastography/FibroScan	Change from baseline in LSM assessed by Liver elastography/FibroScan	From baseline to Months 12 and 24/EOT