RESPONSE: Response to Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and an Inadequate Control to or an Intolerance to Ursodeoxycholic Acid (UDCA)

• ClinicalTrials.gov Identifier: NCT04620733
• Recruitment Status: Completed
• First Posted: November 9, 2020
• Last Update Posted: September 29, 2023
• Sponsor: CymaBay Therapeutics, Inc.
• Information provided by (Responsible Party): CymaBay Therapeutics, Inc.

Tracking Information

• First Submitted Date: November 4, 2020
• First Posted Date: November 9, 2020
• Last Update Posted Date: September 29, 2023
• Actual Study Start Date: April 21, 2021
• Actual Primary Completion Date: August 11, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 4, 2020)

Composite endpoint of ALP and total bilirubin [ Time Frame: 12 months ]

• ALP < 1.67× ULN,
• ≥ 15% decrease in ALP, and
• Total bilirubin ≤1.0× ULN

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 3, 2021)

• Normalization of ALP [ Time Frame: 12 months ]
  Proportion of subjects with ALP ≤1.0× ULN
• Change in baseline numerical rating scale (NRS) [ Time Frame: 6 months ]
  Weekly averaged pruritus NRS in subjects with baseline NRS ≥4. The NRS is a scale of 0 (no itching) to 10 (worst imaginable itching)

Original Secondary Outcome Measures (submitted: November 4, 2020)

• Normalization of ALP [ Time Frame: 12 months ]
  Proportion of subjects with ALP ≤1.0× ULN
• Change in baseline NRS [ Time Frame: 6 months ]
  Weekly averaged pruritus NRS in subjects with baseline NRS ≥4

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: RESPONSE: Response to Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and an Inadequate Control to or an Intolerance to Ursodeoxycholic Acid (UDCA)
• Official 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)
• 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Primary Biliary Cholangitis

Intervention

• Drug: Seladelpar 10 mg
  Seladelpar 10 mg one capsule daily for double-blind period, for a duration of up to 12 months
• Drug: Placebo
  One capsule daily for double-blind period, for a duration of up to 12 months
• Drug: Seladelpar 5 mg
  If down-titration needed, one capsule daily for double-blind period, for a duration of up to 12 months

Study Arms

• Experimental: Seladelpar 10 mg
  Intervention: Drug: Seladelpar 10 mg
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo
• Experimental: Seladelpar 5 mg
  Intervention: Drug: Seladelpar 5 mg

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 1, 2022): 193
• Original Estimated Enrollment (submitted: November 4, 2020): 180
• Actual Study Completion Date: August 11, 2023
• Actual Primary Completion Date: August 11, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Canada, Chile, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Mexico, New Zealand, Poland, Romania, Russian Federation, Spain, Switzerland, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT04620733
• Other Study ID Numbers: CB8025-32048
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: CymaBay Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: CymaBay Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: CymaBay Therapeutics, Inc.
• Verification Date: September 2023