Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis (AFFIRM)

Gilead Sciences

Status and phase: Enrolling; Phase 3

Conditions: Primary Biliary Cholangitis

Treatments: Drug: Seladelpar; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06051617

CB8025-41837

2024-516525-31-00 (Other Identifier)

Details and patient eligibility

About

The goal of this clinical study is to learn more about the study drug, seladelpar, and its effects on clinical outcomes in participants with primary biliary cholangitis (PBC) and compensated cirrhosis.

The primary objective of this study is to evaluate the effect of seladelpar compared to placebo on EFS. EFS is defined as the time from start of treatment to the first occurrence of any of the following adjudicated events up to Week 156.

Enrollment: 402 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Individuals must meet the following criteria to be eligible for study participation:

1. Must be at least 18 years old.
2. Must have a confirmed prior diagnosis of primary biliary cholangitis (PBC)
3. Evidence of cirrhosis
4. CP Score A or B
5. Females of reproductive potential must use at least 1 barrier contraceptive and a second effective birth control method during the study and for at least 90 days after the last dose. Male individuals who are sexually active with female partners of reproductive potential must use barrier contraception, and their female partners must use a second effective birth control method during the study and for at least 90 days after the last dose
6. Individuals must be able to comply with the instructions for study drug administration and be able to complete the study schedule of assessments (SOA)

Exclusion criteria

Individuals must not meet any of the following criteria to be eligible for study participation:

1. Prior exposure to seladelpar

2. A medical condition other than PBC that, in the Investigator's opinion, would preclude full participation in the study

3. History of liver transplantation or actively listed for cadaveric or planned living donor transplant.

4. Decompensated cirrhosis

5. Evidence of portal vein thrombosis based on imaging at time of Screening by Doppler ultrasound or prior evidence by CT or MRI

6. Hospitalization for liver-related complication within 12 weeks of Screening

7. Laboratory parameters at Screening:

   1. Alkaline phosphatase (ALP) < 1.5× Upper limit of normal (ULN) or ≥ 10×ULN
   2. Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≥5×ULN
   3. Total bilirubin (TB) ≤ 0.6 × ULN or ≥ 5 × ULN
   4. Platelet count ≤50×10^3/µL
   5. Albumin ≤2.8 g/dL
   6. Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m^2
   7. MELD score >12. For individuals on anticoagulation medication, baseline International normalized ratio (INR) determination for MELD score calculation should take anticoagulant use into account, in consultation with the Medical Monitor.
   8. Serum alpha-fetoprotein (AFP) >20 ng/mL
   9. INR >1.7

8. CP-C cirrhosis

9. History or presence of other concomitant liver diseases

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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402 participants in 3 patient groups, including a placebo group

Seladelpar

Experimental group

Description:

Participants with Child-Pugh (CP)-A cirrhosis will receive seladelpar 10 mg orally once daily or participants with CP-B cirrhosis will receive seladelpar 5 mg orally once daily, for up to 36 months.

Treatment:

Drug: Seladelpar

Placebo

Placebo Comparator group

Description:

Participants with CP-A or CP-B will be randomized to received placebo to match one capsule daily for up to 36 months.

Treatment:

Drug: Placebo

Open Label Extension Phase

Experimental group

Description:

Participants with CP-A who remained on the study drug at week 156 will receive seladelpar 10 mg daily or participants with CP-B will received seladelpar 5 mg daily for a maximum of 3 years.

Treatment:

Drug: Seladelpar