A Phase 2 Proof-of-Concept Study With a Randomized, Double-Blind, Placebo-Controlled Period, Followed by an Active Treatment Extension Period to Assess the Safety and Efficacy of Seladelpar and Cilofexor in Combination for Primary Biliary Cholangitis
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 132
- 主要终点
- Change From Baseline in Serum Concentration of Alkaline Phosphate (ALP) at Week 24
研究概览
简要总结
The goal of this clinical study is to learn more about the combination of study drugs seladelpar and cilofexor. The study will assess, the safety, tolerability, and effectiveness of the combination drugs versus both seladelpar alone and placebo, in participants with primary biliary cholangitis (PBC).
The primary objective of this study is to determine whether the combination of seladelpar + cilofexor leads to greater alkaline phosphatase (ALP) reduction than seladelpar alone and describe the safety and tolerability of seladelpar + cilofexor.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a diagnosis of PBC as defined by a history of any 2 of the following criteria:
- •ALP above 1.0 × the ULN for at least 6 months
- •Positive antimitochondrial antibody titer (> 1:40 on immunofluorescence or M2 positive by enzyme-linked immunosorbent assay) or positive PBC-specific antinuclear antibodies
- •Documented liver biopsy results consistent with PBC
- •Used ursodeoxycholic acid (UDCA) for the past 12 months (stable dose for > 6 months prior to screening), or intolerant to UDCA (last dose of UDCA > 90 days prior to screening)
- •Have an ALP ≥ 1.67 × ULN at screening
- •Have a negative serum pregnancy test at screening
排除标准
- •Have other causes of liver disease including viral, alcoholic, autoimmune, and metabolic associated steatohepatitis (MASH).
- •Cirrhosis with Child-Pugh Score ≥ 7, corresponding to Class B or C. Individuals with compensated cirrhosis (ie, Child-Pugh Class A) are allowed if they meet all other criteria.
- •Have evidence of portal hypertension or clinically important hepatic decompensation (historic or current), including but not limited to: hepatic encephalopathy, known esophageal or gastric varices, history of liver transplantation, current placement on liver transplant list, Model for End Stage Liver Disease score ≥ 12, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome.
- •Have previous exposure to seladelpar or cilofexor
- •Used obeticholic acid, fenofibrate, bezafibrate, elafibranor, pemafibrate, or saroglitazar within 6 weeks (42 days, inclusive) of screening date
- •Require or expect to require treatment with ≥ 5 mg prednisone (or systemic equivalents) for > 2 weeks during the Blinded Treatment or ATE Periods
- •Are on any systemic drug for antipruritic treatment that has required a dose adjustment in the 30 days before screening, or initiated a systemic antipruritic drug in the 30 days before screening
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Seladelpar (SEL) 10 mg + Placebo-to-Match (PTM) Cilofexor (CILO) Dose A + CILO Dose B
Participants will receive a dose of SEL 10 mg capsule along with PTM CILO Dose A tablets and CILO Dose B tablets, once daily up to 24 weeks.
At completion of Week 24, participants will continue in an Active Treatment Extension (ATE) Period, during which they will receive SEL 10 mg along with either CILO Dose A or Dose B at the original randomized dose in a blinded fashion, up to Week 312.
干预措施: Cilofexor Dose B (Drug)
Seladelpar (SEL) 10 mg + Placebo-to-Match (PTM) Cilofexor (CILO) Dose A + CILO Dose B
Participants will receive a dose of SEL 10 mg capsule along with PTM CILO Dose A tablets and CILO Dose B tablets, once daily up to 24 weeks.
At completion of Week 24, participants will continue in an Active Treatment Extension (ATE) Period, during which they will receive SEL 10 mg along with either CILO Dose A or Dose B at the original randomized dose in a blinded fashion, up to Week 312.
干预措施: PTM Cilofexor Dose A (Drug)
SEL 10 mg + CILO Dose A + PTM CILO Dose B
Participants will receive a dose of SEL 10 mg capsule along with CILO Dose A tablets and PTM CILO Dose B tablets, once daily up to 24 weeks.
At completion of Week 24, participants will continue in an ATE Period, during which they will receive SEL 10 mg along with either CILO Dose A or Dose B at the original randomized dose in a blinded fashion, up to Week 312.
干预措施: PTM Cilofexor Dose B (Drug)
SEL 10 mg + CILO Dose A + PTM CILO Dose B
Participants will receive a dose of SEL 10 mg capsule along with CILO Dose A tablets and PTM CILO Dose B tablets, once daily up to 24 weeks.
At completion of Week 24, participants will continue in an ATE Period, during which they will receive SEL 10 mg along with either CILO Dose A or Dose B at the original randomized dose in a blinded fashion, up to Week 312.
干预措施: Cilofexor Dose A (Drug)
SEL 10 mg + PTM CILO Dose A + PTM CILO Dose B
Participants will receive a dose of SEL 10 mg capsule along with PTM CILO Dose A tablets and PTM CILO Dose B tablets, once daily up to 24 weeks.
At completion of Week 24, participants will continue in an ATE Period, during which they will initiate open-label SEL 10 mg and be re-randomized in a 1:1 ratio to receive CILO Dose A or Dose B in a blinded fashion, up to Week 312.
干预措施: PTM Cilofexor Dose A (Drug)
SEL 10 mg + PTM CILO Dose A + PTM CILO Dose B
Participants will receive a dose of SEL 10 mg capsule along with PTM CILO Dose A tablets and PTM CILO Dose B tablets, once daily up to 24 weeks.
At completion of Week 24, participants will continue in an ATE Period, during which they will initiate open-label SEL 10 mg and be re-randomized in a 1:1 ratio to receive CILO Dose A or Dose B in a blinded fashion, up to Week 312.
干预措施: PTM Cilofexor Dose B (Drug)
PTM SEL 10 mg + PTM CILO Dose A + PTM CILO Dose B
Participants will receive a dose of PTM SEL 10 mg capsule along with PTM CILO Dose A tablets and PTM CILO Dose B tablets once daily up to 24 weeks.
At completion of Week 24, participants will continue in an ATE Period, during which they will initiate open-label SEL 10 mg and be re-randomized in a 1:1 ratio to receive CILO Dose A or Dose B in a blinded fashion, up to Week 312.
干预措施: PTM Seladelpar (Drug)
PTM SEL 10 mg + PTM CILO Dose A + PTM CILO Dose B
Participants will receive a dose of PTM SEL 10 mg capsule along with PTM CILO Dose A tablets and PTM CILO Dose B tablets once daily up to 24 weeks.
At completion of Week 24, participants will continue in an ATE Period, during which they will initiate open-label SEL 10 mg and be re-randomized in a 1:1 ratio to receive CILO Dose A or Dose B in a blinded fashion, up to Week 312.
干预措施: PTM Cilofexor Dose A (Drug)
PTM SEL 10 mg + PTM CILO Dose A + PTM CILO Dose B
Participants will receive a dose of PTM SEL 10 mg capsule along with PTM CILO Dose A tablets and PTM CILO Dose B tablets once daily up to 24 weeks.
At completion of Week 24, participants will continue in an ATE Period, during which they will initiate open-label SEL 10 mg and be re-randomized in a 1:1 ratio to receive CILO Dose A or Dose B in a blinded fashion, up to Week 312.
干预措施: PTM Cilofexor Dose B (Drug)
Seladelpar (SEL) 10 mg + Placebo-to-Match (PTM) Cilofexor (CILO) Dose A + CILO Dose B
Participants will receive a dose of SEL 10 mg capsule along with PTM CILO Dose A tablets and CILO Dose B tablets, once daily up to 24 weeks.
At completion of Week 24, participants will continue in an Active Treatment Extension (ATE) Period, during which they will receive SEL 10 mg along with either CILO Dose A or Dose B at the original randomized dose in a blinded fashion, up to Week 312.
干预措施: Seladelpar (Drug)
SEL 10 mg + PTM CILO Dose A + PTM CILO Dose B
Participants will receive a dose of SEL 10 mg capsule along with PTM CILO Dose A tablets and PTM CILO Dose B tablets, once daily up to 24 weeks.
At completion of Week 24, participants will continue in an ATE Period, during which they will initiate open-label SEL 10 mg and be re-randomized in a 1:1 ratio to receive CILO Dose A or Dose B in a blinded fashion, up to Week 312.
干预措施: Seladelpar (Drug)
SEL 10 mg + CILO Dose A + PTM CILO Dose B
Participants will receive a dose of SEL 10 mg capsule along with CILO Dose A tablets and PTM CILO Dose B tablets, once daily up to 24 weeks.
At completion of Week 24, participants will continue in an ATE Period, during which they will receive SEL 10 mg along with either CILO Dose A or Dose B at the original randomized dose in a blinded fashion, up to Week 312.
干预措施: Seladelpar (Drug)
结局指标
主要结局
Change From Baseline in Serum Concentration of Alkaline Phosphate (ALP) at Week 24
时间窗: Baseline, Week 24
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
时间窗: First dose up to 30 days post last dose (up to 318 weeks)
Percentage of Participants Experiencing Serious Adverse Events (SAEs)
时间窗: First dose up to 30 days post last dose (up to 318 weeks)
次要结局
- Proportion of Participants Achieving the Biochemistry Composite Endpoint at Week 24(Week 24)
- Change From Baseline to Week 24 in Weekly Average Pruritus Numerical Rating Scale (NRS)(Baseline, Week 24)
- Proportion of Participants Achieving ALP Normalization at Week 24(Week 24)