A study to assess efficacy, safety and pharmacokinetics of PLN-74809 in participants with primary sclerosing cholangitis and suspected liver fibrosis)
- Conditions
- Primary sclerosing cholangitis (PSC)MedDRA version: 20.1Level: LLTClassification code 10036732Term: Primary sclerosing cholangitisSystem Organ Class: 100000004871Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2020-001428-33-FR
- Lead Sponsor
- Pliant Therapeutics, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 84
General and Administrative
1. Aged 18 to 75 years, inclusive.
2. Female participants of childbearing potential must use a contraceptive method with a failure rate of <1% per year or remain abstinent (refrain from heterosexual intercourse) during the treatment period and for 1 month after the last dose of study drug.
Male participants with female partners of childbearing potential must agree to use contraceptive measures or remain abstinent (refrain from heterosexual intercourse) during screening and the treatment period and for at least 3 months after the last dose of study drug.
3. Female participants of nonchildbearing potential must be surgically sterile or postmenopausal.
4. Participants must agree to abstain from sperm or egg donation for the duration of the study, through to 3 months or 1 month, respectively, after administration of the last dose of study drug.
5. Able to understand the purpose and procedures that are involved in the study and willing to sign a written informed consent form.
Primary Sclerosing Cholangitis Diagnosis
6. Established clinical diagnosis of large duct PSC based on an abnormal cholangiography as assessed by magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), and/or percutaneous transhepatic
cholangiopancreatography (PTC) in the context of elevated cholestatic liver chemistry.
7. Serum alkaline phosphatase concentration >1 x the upper limit of normal (ULN).
8. Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) concentration =5 × ULN.
9. Serum total bilirubin =1.5 × ULN, in the absence of Gilbert's syndrome or hemolysis. Participants with Gilbert's Syndrome may be enrolled with a direct bilirubin < 0.6 mg/dL.
10. Suspected liver fibrosis, as defined by the following:
- Liver stiffness measurement (LSM) =8 kPa but =14.4 kPa, assessed by FibroScan® OR
- Enhanced Liver Fibrosis (ELF) Score = 7.7 but = 9.8 at Screening OR
- Historical liver biopsy showing fibrosis without cirrhosis (by any scoring system) OR
- Magnetic resonance elastography = 2.4 kPa but = 4.9 kPa
11. Platelet count =140,000/mm3.
12. Albumin =3.3 g/dL.
13. International normalized ratio (INR) =1.3 in the absence of anticoagulant therapy.
14. Serum carbohydrate antigen 19-9 (CA19-9) value =130 U/mL.
Prior and Concomitant Medications
15. If receiving treatment with UDCA, therapy is at a dose of <25 mg/kg/day, has been stable for at least 3 months before screening, will remain stable from screening through Day 1 (baseline), and is expected to remain stable for the duration of the study.
16. If receiving allowed concomitant medications for the treatment of IBD, therapy must be stable from screening and expected to remain stable for the duration of the study.
Medical History and Comorbid Conditions
17. Participants with IBD must have had a colonoscopy showing no evidence of dysplasia within no more than 18 months before screening.
18. Participants with IBD must have no evidence of active disease and a partial Mayo score of <2, with a score of <1 on the Rectal Bleeding domain, between screening through Day 1.
19. Participants with IBD who are receiving treatment with biologics, including tumor necrosis factor-alpha (TNF-a) inhibitors and/or vedolizumab, immunosuppressive agents, or corticosteroids (maximum corticosteroid dose, 10 mg/day of prednisone or equivalent), must have been receiving a stable dose for at least 3 months before screening, the dose must rema
Primary Sclerosing Cholangitis Diagnosis
1. Other causes of liver disease, including secondary sclerosing cholangitis or viral, metabolic, or alcoholic liver disease, as assessed clinically.
2. Known or suspected overlapping clinical and histologic diagnosis of autoimmune hepatitis.
3. Small duct PSC (evidence of PSC on historical liver histology, with normal bile ducts on cholangiography).
Liver Disease Status
4. Presence of a clinically significant dominant stricture based on the combination of radiological, biochemical, and clinical features.
5. Presence of a percutaneous drain or bile duct stent.
6. Serum alkaline phosphatase (ALP) concentration >10 times ULN.
7. Worsening of liver disease, defined as 2 consecutive ALP, ALT or AST measurements obtained >2 weeks apart during the screening period that vary by >30%. This will only be applied to values that are outside
the normal range at Screening Visit 2.
8. Ascending cholangitis within 60 days of screening, as assessed clinically or use of antibiotics for acute cholangitis within 60 days of screening.
9. IgG4-associated cholangitis.
10. Positive anti-mitochondrial antibody.
11. Presence of liver cirrhosis as assessed by historical liver histology, ultrasound-based liver stiffness measurement (FibroScan® value >14.4 kPa), ELF Score > 9.8, MRE > 4.9 kPa and/or signs and symptoms of hepatic decompensation (including, but not limited to, jaundice, ascites, variceal hemorrhage, and/or hepatic encephalopathy).
12. Presence of hepatic impairment, end-stage liver disease, and/or a model for end-stage liver disease (MELD) score =15.
13. Prior or planned liver transplantation during the study.
Medical History and Comorbid Conditions
14. Presence of end-stage renal disease that requires dialysis.
15. History, current clinical or radiological suspicion, or diagnosis of cholangiocarcinoma, other hepatobiliary malignancy, colorectal cancer, or other abdominal malignancy at any time.
16. Human immunodeficiency virus (HIV), hepatitis A virus, hepatitis B virus, and/or hepatitis C virus infection, with the exception of those who have been successfully treated for hepatitis C infection and have achieved sustained virologic response for =1 year
17. History of malignancy within the past 5 years or ongoing malignancy other than basal cell carcinoma, resected noninvasive cutaneous squamous cell carcinoma, or treated cervical carcinoma in situ.
18. Active infection that required antibiotic or antifungal therapy within 30 days before screening.
19. History of unstable or deteriorating cardiac disease within the previous 6 months, including, but not limited to:
a. Unstable angina pectoris or myocardial infarction
b. Congestive heart failure requiring hospitalization
c. Uncontrolled clinically significant arrhythmias
d. Clinically significant electrocardiogram (ECG) abnormalities, including but not limited to, QT interval corrected for heart rate using Fridericia's formula (QTcF) >450 msec for males or >460 msec for females at the Screening visit (including Day -1) or prior to administration of the initial dose of study drug.
20. Surgery within the 4 weeks before administration of study drug.
Prior and Concomitant Medications
21. Currently receiving and expected to remain on treatment during the study with: potent inhibitors or inducers of cytochrome P450 (CYP) 3A4, 2C9 or 2C19; potent inhibitors or inducers of P glycoprotein (P-gp),
breast cancer resistance protein (BCRP) or OATP1B1organic anion transpor
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method