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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04620733




Registration number
NCT04620733
Ethics application status
Date submitted
4/11/2020
Date registered
9/11/2020
Date last updated
5/09/2024

Titles & IDs
Public title
RESPONSE: Response to Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and an Inadequate Control to or an Intolerance to Ursodeoxycholic Acid (UDCA)
Scientific title
RESPONSE: A Placebo-controlled, Randomized, Phase 3 Study to Evaluate the Efficacy and Safety of Seladelpar in Patients With Primary Biliary Cholangitis (PBC) and an Inadequate Response to or an Intolerance to Ursodeoxycholic Acid (UDCA)
Secondary ID [1] 0 0
2020-004348-27
Secondary ID [2] 0 0
CB8025-32048
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 10 mg
Treatment: Drugs - Placebo
Treatment: Drugs - Seladelpar 5 mg

Placebo comparator: Placebo - Participants will receive placebo to match seladelpar, orally, once daily, for a duration of up to 12 months.

Experimental: Seladelpar - Participants will receive seladelpar 10 mg (or 5 mg down-titrated, for those participants who met specific safety monitoring criteria or had tolerability issues), orally, once daily, for a duration of up to 12 months.


Treatment: Drugs: Seladelpar 10 mg
Seladelpar 10 mg one capsule daily for double-blind period, for a duration of up to 12 months

Treatment: Drugs: Placebo
One capsule daily for double-blind period, for a duration of up to 12 months

Treatment: Drugs: Seladelpar 5 mg
If down-titration needed, one capsule daily for double-blind period, for a duration of up to 12 months
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Response Criteria for the Composite Endpoint of ALP <1.67 × Upper Limit of Normal (ULN), =15% Reduction in ALP, and Total Bilirubin = 1.0× ULN at Month 12
Timepoint [1] 0 0
Month 12
Primary outcome [2] 0 0
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Timepoint [2] 0 0
First dose date up to last dose plus 30 days (up to 13.4 months)
Primary outcome [3] 0 0
Percentage of Participants With Shift of = 2 CTCAE Grades From Baseline in Treatment-emergent Laboratory Abnormalities Related to Hematology and Select Liver Biochemistry
Timepoint [3] 0 0
First dose date up to last dose (up to 13.4 months)
Secondary outcome [1] 0 0
Percentage of Participants With ALP =1.0× ULN at Month 12
Timepoint [1] 0 0
Month 12
Secondary outcome [2] 0 0
Change From Baseline in Weekly Averaged Pruritus Numerical Rating Scale (NRS) in Participants With NRS = 4 at Month 6
Timepoint [2] 0 0
Baseline, Month 6

Eligibility
Key inclusion criteria
Key

* Must have given written informed consent (signed and dated) and any authorizations required by local law.
* Male or female with a definitive diagnosis of primary biliary cholangitis (PBC).
* Ursodeoxycholic acid (UDCA) for the past 12 months (stable dose for >3 months prior to screening) or intolerant to UDCA (last dose of UDCA >3 months prior to screening).
* Laboratory parameters measured by the Central Laboratory at screening:

* Alkaline phosphatase (ALP) =1.67× ULN (upper limit of normal)
* Aspartate aminotransferase (AST) =3× ULN
* Alanine aminotransferase (ALT) =3× ULN
* Total bilirubin =2× ULN
* Estimated glomerular filtration rate (eGFR) >45 mL/min/1.73 m^2 (calculated by the Modification of Diet in Renal Disease study equation).
* International normalized ratio (INR) below 1.1× ULN (For individuals on anticoagulation therapy, INR must be maintained in the range required for prophylaxis for their specific disease).
* Platelet count =100 ×10^3/µL.
* 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.

Key
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Previous exposure to seladelpar (MBX-8025).
* A medical condition other than PBC that, in the investigator's opinion, would preclude full participation in the study (e.g., cancer) or confound its results (e.g., Paget's disease, any active infection).
* Advanced PBC as defined by the Rotterdam criteria (albumin below the lower limit of normal and total bilirubin above 1.0 × ULN).
* Presence of clinically important hepatic decompensation, including the following:

* History of liver transplantation, current placement on liver transplantation list, or current Model for End-Stage Liver Disease (MELD) score =12. For individuals on anticoagulation medication, evaluation of the baseline INR, in concert with their current dose adjustments of their anticoagulant medication, will be taken into account when calculating the MELD score. This will be done in consultation with the medical monitor.
* Complications of portal hypertension, including known esophageal varices, history of variceal bleeds or related interventions (e.g., transjugular intrahepatic portosystemic shunt placement), ascites, and hepatic encephalopathy.
* Cirrhosis with complications, including history or presence of spontaneous bacterial peritonitis, hepatocellular carcinoma, or hepatorenal syndrome.
* Other chronic liver diseases:

* Current features of autoimmune hepatitis (AIH) as determined by the investigator based on immunoserology, liver biochemistry, or historic confirmed liver histology.
* PSC determined by the presence of diagnostic cholangiographic findings.
* History or clinical evidence of alcoholic liver disease.
* History or clinical evidence of alpha-1-antitrypsin deficiency.
* History of biopsy confirmed nonalcoholic steatohepatitis (NASH).
* History or evidence of Gilbert's syndrome with elevated total bilirubin.
* History or evidence of hemochromatosis.
* Hepatitis B, defined as the presence of hepatitis B surface antigen.
* Hepatitis C, defined as the presence of hepatitis C virus ribonucleic acid.
* History, evidence, or high suspicion of hepatobiliary malignancy based on imaging, screening laboratory values, and/or clinical symptoms.
* Known history of human immunodeficiency virus (HIV) or positive antibody test at screening
* Clinically important alcohol consumption, defined as more than 2 drink units per day (equivalent to 20 g) in women and 3 drink units per day (equivalent to 30 g) in men, or inability to quantify alcohol intake reliably.
* History of malignancy diagnosed or treated, actively or within 2 years, or ongoing evaluation for malignancy; localized treatment of squamous or noninvasive basal cell skin cancers and cervical carcinoma in situ is allowed if appropriately treated prior to screening.
* Treatment with obeticholic acid (OCA) or fibrates (e.g., bezafibrate, fenofibrate, elafibranor, lanifibranor, pemafibrate, saroglitizar) 6 weeks prior to screening.
* Treatment with colchicine, methotrexate, azathioprine, or long-term systemic corticosteroids (>2 weeks) during 2 months prior to screening
* Treatment with anti-pruritic drugs (e.g., cholestyramine, naltrexone, rifampicin, sertraline, or any experimental approach) must be on a stable dose within 1 month prior to screening
* Treatment with any other investigational therapy or device within 30 days or within 5 half-lives, whichever is longer, prior to screening
* For females, pregnancy or breastfeeding.
* Any other condition(s) that would compromise the safety of the individual or compromise the quality of the clinical study, as judged by the investigator.
* Immunosuppressant therapies.
* Other medications that effect liver or gastrointestinal (GI) functions, such as absorption of medications or the roux-en-y gastric bypass procedure, may be prohibited and should be discussed with the medical monitor on a case-by-case basis.
* Active Coronavirus Disease-2019 (COVID-19) infection during Screening.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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
21/04/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
11/08/2023
Sample size
Target
Accrual to date
Final
193
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
Royal Brisbane & Women's Hospital - Herston
Recruitment hospital [3] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [4] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
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Illinois
Country [7] 0 0
United States of America
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Louisiana
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United States of America
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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Missouri
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New York
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North Carolina
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Ohio
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Pennsylvania
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Texas
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Virginia
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Washington
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Argentina
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Buenos Aires
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Argentina
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Caba
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Austria
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Wels
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Belgium
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Antwerpen
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Belgium
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Liège
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Belgium
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Oost-Vlaanderen
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Belgium
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Canada
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Ontario
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Chile
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Coquimbo
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Chile
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Los Ríos
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Chile
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Valparaíso
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Czechia
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Ostrava
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Aalborg
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Hvidovre
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Germany
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Ancona
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Firenze
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Gyeonggido
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Samara
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Stavropol
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Barcelona
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Malaga
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Switzerland
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Zürich
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Istanbul
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Izmir
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Ukraine
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Kharkiv
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Ukraine
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Kyiv
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United Kingdom
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Devon
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United Kingdom
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Hampshire
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United Kingdom
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London, City Of
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United Kingdom
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Nottinghamshire
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Oxfordshire
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United Kingdom
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Birmingham
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United Kingdom
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Hull
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United Kingdom
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London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
CymaBay Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT04620733