AFFIRM: A Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Effect of Seladelpar on Clinical Outcomes in Patients with Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gilead Sciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

14 Jul 2025 → ongoing

Decision date (initial)

2025-06-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Gilead Sciences, Inc.

External identifiers

EU CT number

2024-516525-31-01

ClinicalTrials.gov

NCT06051617

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Efficacy: 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:
Death by any cause
Liver Transplantation
MELD Score ≥ 15
Ascites Requiring Treatment
Hospitalization for any of the following qualifying events:
Esophageal or gastric variceal bleeding.
Hepatic encephalopathy.
Spontaneous bacterial peritonitis confirmed by WBC count, differential, and/or positive growth from aerobic and/or anaerobic blood culture bottles via diagnostic paracentesis.

Safety: To evaluate the safety of seladelpar over 156 weeks of treatment compared with placebo.

Secondary objectives 4

1. Overall survival
2. Liver transplant-free survival (LTFS), defined as time from start of treatment to the first occurrence of liver-related death or liver transplantation
3. Time to hospitalization for any of the following qualifying adjudicated events Esophageal or gastric variceal bleeding. Hepatic encephalopathy. Spontaneous bacterial peritonitis confirmed by WBC count, differential, and/or positive growth from aerobic and/or anaerobic blood culture bottles via diagnostic paracentesis.
4. Time to each of the other adjudicated PBC clinical events.

Conditions and MedDRA coding

Primary Biliary Cholangitis

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Must be at least 18 years old.
2. Must have a confirmed prior diagnosis of PBC
3. Evidence of cirrhosis
4. CP class 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 subjects 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. Subjects 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 9

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 during screening: a. ALP < 1.5× ULN b. TB ≤0.6×ULN or ≥5×ULN c. TB ≥ 5× ULN d. Platelet count ≤ 50×103/μL e. Albumin ≤ 2.8 g/dL f. Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 g. MELD score > 12. For subjects on anticoagulation medication, baseline INR determination for MELD score calculation should take anticoagulant use into account, h. Serum alpha-fetoprotein (AFP) > 20 ng/mL i. INR > 1.7
8. CP-C cirrhosis
9. History or presence of other concomitant liver diseases

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. EFS as measured by the time from start of treatment to the first occurrence of any of the following adjudicated events up to week 156: a. Death by any cause b. Liver transplantation c. MELD Score ≥ 15 d. Ascites requiring treatment e. Hospitalization for any of the following qualifying events: i.Esophageal or gastric variceal bleeding ii.Hepatic encephalopathy iii. Spontaneous bacterial peritonitis

Secondary endpoints 4

1. Overall survival, defined as time from start of treatment to death from any cause up to Week 156
2. LTFS, defined as time from start of treatment to the first occurrence of any of the following up to Week 156: a. Liver-related death b. Liver transplantation
3. Time to hospitalization for qualifying PBC clinical events from start of treatment up to Week 156:
4. Time to each of the other adjudicated PBC clinical events from start of treatment up to Week 156: a. MELD Score ≥ 15 b. Ascites requiring treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gilead Sciences Inc.

Sponsor organisation

Gilead Sciences Inc.

Address

333 Lakeside Drive

City

Foster City

Postcode

94404-1147

Country

United States

Scientific contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Public contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Third parties 9

Locations

13 EU/EEA countries · 59 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 190 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications