A study to evaluate the safety and tolerability of seladelpar in subjects with primary biliary cholangitis

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

Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

26 May 2021 → ongoing

Decision date (initial)

2024-07-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Gilead Sciences, Inc.

External identifiers

EU CT number

2024-511753-22-00

EudraCT number

2020-005198-29

ClinicalTrials.gov

NCT03301506

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy, Pharmacokinetic

To evaluate the long-term safety and tolerability of seladelpar

Secondary objectives 1

1. To evaluate the long-term efficacy of seladelpar, and the effect of seladelpar on patient-reported outcomes (pruritus)

Conditions and MedDRA coding

Primary Biliary Cholangitis

Study design 9 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002527-PIP01-18

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Must have given informed consent (signed and dated)
2. Participated in a prior PBC study with seladelpar (e.g., including CB8025-21629, CB8025-31735, or CB8025-31731), current PBC studies (CB8025-32048 or CB8025-21838), or completed a future PBC study with seladelpar that allows rollover into CB8025-31731-RE, and meet eligibility criteria for the current study.
3. Females of reproductive potential must use at least one 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

Exclusion criteria 23

1. Exclusion criteria are only applicable for subjects with a study drug interruption greater than 4 weeks prior to Day 1 of this study and for subjects who participated in CB8025-21838 irrespective of seladelpar interruption 1. Treatment-related AE leading to study drug discontinuation in a previous PBC study with seladelpar
2. A medical condition, other than PBC, that in the Investigator's opinion would preclude full participation in the study or confound its results (e.g., cancer, any active infection)
3. AST or ALT above 3 × the upper limit of normal (ULN)
4. Total bilirubin above 2 × ULN
5. MELD score ≥ 12. For subjects on anticoagulation medication, evaluation of the baseline INR, in concert with any current dose adjustments in anti-coagulant medications, will be taken into account when calculating this score. This will be done in consultation with the medical monitor.
6. Evidence of advanced PBC as defined by the Rotterdam criteria (albumin below 1 × lower limit of normal AND total bilirubin above 1 × ULN)
7. Estimated glomerular filtration rate ≤ 45 mL/min/1.73 m2 (calculated by Modification of Diet in Renal Disease formula)
8. Auto-immune hepatitis
9. Primary sclerosing cholangitis
10. Known history of alpha-1-antitrypsin deficiency
11. Known history of chronic viral hepatitis
12. For females, pregnancy or breast-feeding
13. Use of colchicine, methotrexate, azathioprine or long-term use of systemic steroids (e.g. prednisone, prednisolone, budesonide) (>2 weeks) within 2 months prior to Screening. See the concomitant medication section for additional medications that may be excluded.
14. Current use of fibrates or use of fibrates within 3 months prior to Screening
15. Current use of obeticholic acid or use of obeticholic acid within 3 months prior to Screening
16. Use of an experimental or unapproved treatment for PBC within 3 months prior to Screening
17. History of malignancy diagnosed or treated, actively or within 2 years, or active evaluation for malignancy; localized treatment of squamous or non-invasive basal cell skin cancers and cervical carcinoma in-situ is allowed if appropriately treated prior to Screening
18. Treatment with any other investigational therapy or medical device within 30 days or within 5 half-lives, whatever is longer, prior to Screening
19. Any other condition(s) that would compromise the safety of the subject or compromise the quality of the clinical study as judged by the Investigator
20. Immunosuppressant therapies (e.g., cyclosporine, tacrolimus, antiTNF or other immunosuppressive biologics)
21. Other medications that effect liver or GI functions such as absorption of medications may be prohibited and should be discussed with the medical monitor on a case-by-case basis
22. Positive for: a. Hepatitis B, defined as the presence of hepatitis B surface antigen b. Hepatitis C, defined as the presence of hepatitis C virus ribonucleic acid c. Human immunodeficiency virus (HIV) antibody
23. Active COVID-19 infection during Screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Treatment-emergent AEs (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Version 5.0), biochemistry and hematology results are collected

Secondary endpoints 3

1. Occurrence of the following adjudicated PBC clinical outcomes: -Overall death -Liver transplantation -MELD score ≥ 15 for at least 2 consecutive visits -Ascites requiring treatment -Hospitalization for new onset or recurrence, of any: -Variceal bleeding, Hepatic encephalopathy, Spontaneous bacterial peritonitis
2. Biochemical markers: -Response on composite of ALP and total bilirubin -Proportion of subjects with normalization of ALP -Relative and absolute changes of the following: -Alkaline phosphatase (ALP) -Aspartate aminotransferase (AST) -Alanine aminotransferase (ALT) -Gamma-glutamyl transferase (GGT) -Bilirubin (total, direct, indirect)
3. Change from Baseline in pruritus NRS

Investigational products

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

Test 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 17

Locations

12 EU/EEA countries · 29 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 154 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