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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03602560




Registration number
NCT03602560
Ethics application status
Date submitted
18/07/2018
Date registered
27/07/2018
Date last updated
2/08/2022

Titles & IDs
Public title
ENHANCE: Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and an Inadequate Response to or an Intolerance to Ursodeoxycholic Acid (UDCA)
Scientific title
A 52-week, Placebo-controlled, Randomized, Phase 3 Study to Evaluate the Safety and Efficacy of Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and an Inadequate Response to or an Intolerance to Ursodeoxycholic Acid (UDCA)
Secondary ID [1] 0 0
CB8025-31735
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Biliary Cholangitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Infection 0 0 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - seladelpar 5-10 mg
Treatment: Drugs - seladelpar 10 mg
Treatment: Drugs - Placebo

Experimental: Seladelpar 5-10 mg -

Experimental: Seladelpar 10 mg -

Placebo comparator: Placebo -


Treatment: Drugs: seladelpar 5-10 mg
Seladelpar 5 mg for 6 months and then titrating up to 10 mg based on tolerability and response for remainder of double-blind period. After completion of the 1-year double-blind period subjects will be offered the opportunity to enter an open label long term safety study. Subjects will continue the seladelpar dose (5 or 10 mg) received during the double-blinded study

Treatment: Drugs: seladelpar 10 mg
Seladelpar 10 mg for double-blind period. After completion of the 1-year double-blind period subjects will be offered the opportunity to enter an open label safety study. Subjects will continue the seladelpar dose (10 mg) received during the double-blinded study

Treatment: Drugs: Placebo
One capsule daily for double-blind period. After completion of the 1-year double-blind period subjects will be offered the opportunity to enter an open label long term safety study. Subjects on placebo will be re-randomized to initiate seladelpar at 5 or 10 mg once daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Response to Composite Endpoint of ALP <1.67 × Upper Limit of Normal [ULN], =15% Reduction in ALP, and Total Bilirubin = ULN) at Month 3
Timepoint [1] 0 0
Month 3
Secondary outcome [1] 0 0
Percentage of Participants With Response Defined by Normalized Alkaline Phosphatase Levels at Month 3
Timepoint [1] 0 0
Month 3
Secondary outcome [2] 0 0
Change From Baseline in Pruritus NRS for Subjects With Baseline NRS =4 at Month 3
Timepoint [2] 0 0
Month 3

Eligibility
Key inclusion criteria
1. Must have given written informed consent (signed and dated) and any authorizations required by local law
2. 18 to 75 years old (inclusive)
3. Male or female with a diagnosis of PBC, by at least two of the following criteria:

* History of AP above ULN for at least six months
* Positive anti-mitochondrial antibody (AMA) titers (>1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay [ELISA]) or positive PBC-specific antinuclear antibodies
* Documented liver biopsy result consistent with PBC
4. On a stable and recommended dose of UDCA for the past twelve months OR intolerant to UDCA (last dose of UDCA > 3 months prior to Screening)
5. AP = 1.67 × ULN
6. 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
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous exposure to seladelpar (MBX-8025)
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)
3. AST above 3 × ULN
4. ALT above 3 × ULN
5. Total bilirubin above 2.0 × ULN
6. Advanced PBC as defined by the Rotterdam criteria (albumin below LLN AND total bilirubin above 1 × ULN)
7. Creatine kinase (CK) above 1.0 × ULN
8. eGFR below 60 mL/min/1.73 m2 (calculated by MDRD formula)
9. International normalized ratio (INR) above 1.0 × ULN
10. Platelet count below 100 × 103/µL
11. Presence of clinically significant hepatic decompensation, including:

* History of liver transplantation, current placement on liver transplantation list, or current MELD score = 15
* Complications of portal hypertension, including known esophageal varices, history of variceal bleeds or related interventions (e.g., transjugular intrahepatic portosystemic shunt placement), relevant ascites, hepatic encephalopathy
* Cirrhosis with complications, including history or presence of spontaneous bacterial peritonitis
12. Other chronic liver diseases:

* Current features of auto-immune hepatitis as determined by the investigator based on immunoserology, liver biochemistry and histology
* Primary sclerosing cholangitis determined by presence of diagnostic cholangiographic findings
* History or clinical evidence of alcoholic liver disease
* History or clinical evidence of alpha-1-antitrypsin deficiency
* Biopsy confirmed nonalcoholic steatohepatitis
* History or evidence of Gilbert' Syndrome with elevated total bilirubin
* History or evidence of hemochromatosis
* Hepatitis B defined as presence of hepatitis B surface antigen (HBsAg)
* Hepatitis C defined as presence of HCV RNA
13. Known history of HIV
14. Evidence of significant alcohol consumption
15. Evidence of drug abuse
16. Subjects with inadequate response to obeticholic acid (OCA) or intolerance to OCA: OCA must be discontinued 30 days prior to Screening
17. Use of colchicine, methotrexate, azathioprine, or long-term systemic corticosteroids (> 2 weeks) within two months prior to Screening
18. Use of fibrates within 30 days prior to Screening
19. Use of simvastatin within 7 days prior to Screening
20. Use of an experimental or unapproved treatment for PBC within 30 days prior to Screening
21. Use of experimental or unapproved immunosuppressant within 30 days prior to Screening
22. Treatment with any other investigational therapy or device within 30 days or within five half-lives, whatever is longer, prior to Screening
23. For females, pregnancy or breast-feeding
24. 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/02/2020
Sample size
Target
Accrual to date
Final
265
Recruitment in Australia
Recruitment state(s)
ACT,QLD,VIC,WA
Recruitment hospital [1] 0 0
The Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Royal Brisbane & Women's Hospital - Herston
Recruitment hospital [3] 0 0
St Vincents Hospital Melbourne - Fitzroy
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [5] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment postcode(s) [5] 0 0
6000 - Perth
Recruitment outside Australia
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Birmingham
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
A 52-week, placebo-controlled, randomized, Phase 3 study to evaluate the safety and efficacy of seladelpar in subjects with primary biliary cholangitis (PBC) and an inadequate response to or intolerance to ursodeoxycholic acid (UDCA)

The participants might enter the ongoing open-label safety study (NCT03301506) following this double-blind study.
Trial website
https://clinicaltrials.gov/study/NCT03602560
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
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Address 0 0
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Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03602560