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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04620733




Registration number
NCT04620733
Ethics application status
Date submitted
4/11/2020
Date registered
9/11/2020
Date last updated
29/09/2023

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
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

Experimental: Seladelpar 10 mg -

Placebo Comparator: Placebo -

Experimental: Seladelpar 5 mg -


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
Composite endpoint of ALP and total bilirubin
Timepoint [1] 0 0
12 months
Secondary outcome [1] 0 0
Normalization of ALP
Timepoint [1] 0 0
12 months
Secondary outcome [2] 0 0
Change in baseline numerical rating scale (NRS)
Timepoint [2] 0 0
6 months

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 definitive diagnosis of PBC

4. 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)

5. Laboratory parameters measured by the Central Laboratory at screening:

1. ALP =1.67× ULN

2. Aspartate aminotransferase (AST) =3× ULN

3. ALT =3× ULN

4. Total bilirubin =2× ULN

5. Estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 (calculated by the
Modification of Diet in Renal Disease study equation)

6. International normalized ratio (INR) below 1.1× ULN For subjects on
anticoagulation therapy, INR must be maintained in the range required for
prophylaxis for their specific disease.

7. Platelet count =100×103/µL

NOTE: PT, INR, and platelets can be performed locally at the Screening Visit, if
deemed necessary by the investigator after consultation with the medical monitor, in
cases where centrally read samples are deemed invalid.

6. 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
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 (e.g., cancer) or confound its results (e.g., Paget's
disease, any active infection).

3. Advanced PBC as defined by the Rotterdam criteria (albumin below the lower limit of
normal AND total bilirubin above 1.0× ULN)

4. Presence of clinically important hepatic decompensation, including the following:

1. History of liver transplantation, current placement on liver transplantation
list, or current Model for End-Stage Liver Disease (MELD) score =12. For subjects
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.

2. Complications of portal hypertension, including known esophageal varices, history
of variceal bleeds or related interventions (ege.g., transjugular intrahepatic
portosystemic shunt placement), ascites, and hepatic encephalopathy.

3. Cirrhosis with complications, including history or presence of spontaneous
bacterial peritonitis, hepatocellular carcinoma, or hepatorenal syndrome.

5. Other chronic liver diseases:

1. Current features of AIH as determined by the investigator based on
immunoserology, liver biochemistry, or historic confirmed liver histology.

2. PSC determined by the presence of diagnostic cholangiographic findings.

3. History or clinical evidence of alcoholic liver disease.

4. History or clinical evidence of alpha-1-antitrypsin deficiency.

5. History of biopsy confirmed NASH.

6. History or evidence of Gilbert's syndrome with elevated total bilirubin.

7. History or evidence of hemochromatosis.

8. Hepatitis B, defined as the presence of hepatitis B surface antigen.

9. Hepatitis C, defined as the presence of hepatitis C virus ribonucleic acid.

10. History, evidence, or high suspicion of hepatobiliary malignancy based on
imaging, screening laboratory values, and/or clinical symptoms.

6. Known history of human immunodeficiency virus (HIV) or positive antibody test at
screening

7. 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.

8. 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.

9. Treatment with obeticholic acid (OCA) or fibrates (e.g., bezafibrate, fenofibrate,
elafibranor, lanifibranor, pemafibrate, saroglitizar) 6 weeks prior to screening

10. Treatment with colchicine, methotrexate, azathioprine, or long-term systemic
corticosteroids (>2 weeks) during 2 months prior to screening

11. 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

12. Treatment with any other investigational therapy or device within 30 days or within 5
half-lives, whichever is longer, prior to screening

13. For females, pregnancy or breastfeeding

14. 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

15. Immunosuppressant therapies

16. Other medications that effect liver or 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.

17. Active COVID-19 infection during Screening.

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
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United States of America
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Arizona
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Arkansas
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California
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Illinois
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Louisiana
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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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Caba
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Wels
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Antwerpen
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Liège
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Kharkiv
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Kyiv
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Devon
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Hampshire
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London, City Of
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Nottinghamshire
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Oxfordshire
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Birmingham
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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
CymaBay Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To evaluate the treatment effect of seladelpar on composite biochemical improvement in
cholestasis markers based on ALP and total bilirubin and to evaluate the safety of seladelpar
over 12 months of treatment compared to placebo
Trial website
https://clinicaltrials.gov/ct2/show/NCT04620733
Trial related presentations / publications
Public notes

Contacts
Principal investigator
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Address 0 0
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Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
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Phone 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/ct2/show/NCT04620733