RESPONSE: Response to Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and an Inadequate Control to or an Intolerance to Ursodeoxycholic Acid (UDCA)
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|ClinicalTrials.gov Identifier: NCT04620733|
Recruitment Status : Active, not recruiting
First Posted : November 9, 2020
Last Update Posted : February 15, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Primary Biliary Cholangitis||Drug: Seladelpar 10 mg Drug: Placebo Drug: Seladelpar 5 mg||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||193 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|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)|
|Actual Study Start Date :||April 21, 2021|
|Estimated Primary Completion Date :||August 2023|
|Estimated Study Completion Date :||August 2023|
|Experimental: Seladelpar 10 mg||
Drug: Seladelpar 10 mg
Seladelpar 10 mg one capsule daily for double-blind period, for a duration of up to 12 months
|Placebo Comparator: Placebo||
One capsule daily for double-blind period, for a duration of up to 12 months
|Experimental: Seladelpar 5 mg||
Drug: Seladelpar 5 mg
If down-titration needed, one capsule daily for double-blind period, for a duration of up to 12 months
- 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
- 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)
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|Ages Eligible for Study:||18 Years to 75 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Must have given written informed consent (signed and dated) and any authorizations required by local law
- 18 to 75 years old (inclusive)
- Male or female with a definitive diagnosis of PBC
- 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:
- ALP ≥1.67× ULN
- Aspartate aminotransferase (AST) ≤3× ULN
- ALT ≤3× ULN
- Total bilirubin ≤2× ULN
- Estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 (calculated by the Modification of Diet in Renal Disease study equation)
- 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.
- 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.
- 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
- 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 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.
- 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.
- Cirrhosis with complications, including history or presence of spontaneous bacterial peritonitis, hepatocellular carcinoma, or hepatorenal syndrome.
Other chronic liver diseases:
- Current features of 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 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 subject or compromise the quality of the clinical study, as judged by the investigator
- Immunosuppressant therapies
- 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.
- Active COVID-19 infection during Screening.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04620733
|Responsible Party:||CymaBay Therapeutics, Inc.|
|Other Study ID Numbers:||
|First Posted:||November 9, 2020 Key Record Dates|
|Last Update Posted:||February 15, 2023|
|Last Verified:||September 2022|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Primary Biliary Cholangitis (PBC)
Liver Cirrhosis, Biliary
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents