A Randomized, Double-blind, Placebo-controlled, Phase 2a Study With Open-label Extension to Evaluate the Safety and Efficacy of Zetomipzomib (KZR-616) in Patients With Autoimmune Hepatitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 27
- 主要终点
- Patients Who Achieved Complete Biochemical Response
研究概览
简要总结
This was a Phase 2a, multi-center, placebo-controlled study in which patients with autoimmune hepatitis received zetomipzomib or placebo in addition to standard-of-care for 24 weeks; an optional open-label extension period allowed participants to receive zetomipzomib (KZR-616) for an additional 24 weeks of treatment.
详细描述
This was a Phase 2a, multi-center, randomized, double-blind, placebo-controlled study with an open-label extension to evaluate safety, tolerability, and efficacy of zetomipzomib in patients with autoimmune hepatitis (AIH) who have not benefited from standard-of-care treatment, had an incomplete response to ≥3 months of standard-of-care treatment, or had a disease flare after standard of care.
Zetomipzomib or placebo were administered weekly for a 24-week treatment period in addition to standard-of-care (glucocorticoids), followed by a 4-week off-treatment safety follow-up period. Zetomipzomib and placebo was administered subcutaneously (SC) once weekly.
At the end of the 24-week treatment period, eligible participants from both the zetomipzomib- and placebo-treated arms who completed the double-blind treatment period could enroll in the open-label extension period to receive up to an additional 24 weeks of treatment with zetomipzomib.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •for the Double-blind Treatment Period:
- •Must be aged ≥18 years.
- •Must have a clinical diagnosis of AIH and signs of active disease despite standard-of-care therapy for ≥3 months or disease flare after experiencing complete remission induced by standard-of-care treatment, including:
- •Screening ALT values that are 1.25 to 10 times the upper limit of the normal range (ULN)
- •Liver biopsy results with Ishak score (modified HAI) ≥5/18 indicating active AIH, from a biopsy performed at Screening, or within 6 months prior to Screening
- •Mild or no hepatic impairment (Child Pugh category A)
- •Must be willing to use and taper glucocorticoid therapy.
- •Must be willing to use effective contraception.
排除标准
- •for the Double-blind Treatment Period:
- •Have a concomitant diagnosis of primary biliary sclerosis, primary sclerosing cholangitis, IgG 4 related cholangitis, drug related AIH (at Screening) or a history of drug-related AIH.
- •Have clinical evidence of significant unstable or uncontrolled diseases other than the disease under study.
- •Are receiving oral or injectable immunomodulating treatment for any other autoimmune disease prior to enrollment in the study. Patients who have been using such treatments must follow the specified washout periods.
- •Have an active infection (eg, acute hepatitis E, cytomegalovirus, or Epstein-Barr virus) requiring systemic therapy with antibiotic, antiviral, or antifungal treatment, or has had any febrile illness within 7 days prior to Day -
- •Have a history of thyroiditis, celiac disease, or other autoimmune disorder known to be associated with transaminitis.
- •Have liver cirrhosis with significant impairment of liver function (Child Pugh category B or C) or have decompensated cirrhosis.
- •Patients with histology confirmed coincident non-alcoholic steatohepatitis.
- •Key Inclusion Criteria for the Open-label Extension Period:
- •Same as Double-blind Treatment Period inclusion criteria, except the following modifications:
- •ALT value can be normal or, if elevated, in the range of 1.25 to 10 times the upper limit of normal
- •Must have completed the Double-blind Period study visits through Week 24, including all Week 24 Visit assessments.
- •Must be willing to maintain glucocorticoid therapy or continue to taper glucocorticoid therapy.
- •Key Exclusion Criteria for the Open-label Extension Period:
- •Same as Double-blind Treatment Period except no need to re-test for HIV, HBV, HCV, and TB.
研究组 & 干预措施
zetomipzomib + standard-of-care (glucocorticoids)
Initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period.
干预措施: zetomipzomib (Drug)
placebo + standard-of-care (glucocorticoids)
Initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period.
干预措施: placebo (Drug)
zetomipzomib + standard-of care (glucocorticoids) open-label extension period
Initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment.
干预措施: zetomipzomib in open-label extension (Drug)
结局指标
主要结局
Patients Who Achieved Complete Biochemical Response
时间窗: Week 12, Week 16, Week 20, and Week 24
The number of patients who achieve complete biochemical response (CR), defined as normal ALT, AST, and IgG values (if IgG level is elevated at Baseline) with glucocorticoid dose not higher than starting dose (at Baseline), by Week 24 of the Double-Blind Treatment Period. Analyses were also conducted at Week 12, Week 16, and Week 20.
The Safety and Tolerability of Zetomipzomib
时间窗: Baseline through end of study visit (DBTP, Week 28 and OLE, Up to Week 24)
Proportion of participants who experience AEs (adverse events) and SAEs (serious adverse events) during the double-blind treatment period (DBTP) and the open-label extension (OLE).
Proportion of Participants Experiencing a Disease Flare Among the Participants Who Achieved a CR During the Double-blind Treatment Period
时间窗: Start of open-label extension (OLE) period through End of Study (EOS) up to OLE Week 25
Proportion of participants experiencing a disease flare among the participants who achieved a complete biochemical response (CR) during the double-blind treatment period.
次要结局
- Alanine Aminotransferase (ALT)(Weeks 12, 16, 20, and 24)
- Partial Response(Weeks 12, 16, 20, and 24)
- Time to Complete Response(Baseline through Week 24)
- Disease Flare After CR(Week 24)
- Treatment Failures(Week 24)
- Complete Response With Glucocorticoid Taper to ≤10 mg(Weeks 12, 16, 20, and 24)
- Complete Response With Glucocorticoid Taper to 0 mg(Weeks 12, 16, 20, and 24)
- Complete Response With Glucocorticoid Taper to ≤5 mg(Weeks 12, 16, 20, and 24)
- Partial Response With Glucocorticoid Taper to ≤10 mg(Week 24)
- Partial Response With Glucocorticoid Taper to ≤5 mg(Week 24)
- Partial Response With Glucocorticoid Taper to 0 mg(Week 24)