A Phase 1/2, First-in-Human, Multi-Arm, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Efficacy of VV-14303, an Adeno-associated Virus Vector-mediated Fibroblast Growth Factor 21 (FGF21) Gene Therapy, in Adults With Metabolic Dysfunction-associated Steatohepatitis (MASH)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 56
- 试验地点
- 6
- 主要终点
- Incidence and severity of adverse events, abnormal clinical laboratory values, abnormal physical exams, abnormal vital signs, abnormal ECGs, and abnormal imaging
研究概览
简要总结
A Study of VV-14303 for the Treatment of Metabolic dysfunction-associated steatohepatitis (MASH)
详细描述
A Phase 1/2, First-in-Human, Multi-Arm, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of VV-14303, an Adeno-associated Virus Vector-mediated Fibroblast Growth Factor 21 (FGF21) Gene Therapy, in Adults with Metabolic dysfunction associated steatohepatitis (MASH) (the RESTORE Study)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Participant is capable of providing signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol
- •Must be 18 to 75 years of age (inclusive) at Screening
- •Body Mass Index (BMI) of 25 to <40 kg/m2 (inclusive)
- •Male participants must agree to use a highly effective contraception during the Treatment Period and at least 12 months after administration of VV-
- •Female participants must not be a woman of child-bearing potential (WOCBP)
- •Biopsy-confirmed MASH
- •Previous history or presence of ≥2 of the following metabolic risk factors: obesity (BMI ≥25 kg/m²), hypertension (blood pressure [BP] ≥140/90 mmHg or on antihypertensive medication), dyslipidemia (triglycerides ≥150 mg/dL or high-density lipoprotein cholesterol [HDL-C] <40 mg/dL in men/<50 mg/dL in women or on lipid-lowering therapy), type 2 diabetes mellitus
- •Must be willing to refrain from the donation of blood, plasma, platelets, eggs, or sperm during the 12-month post-treatment follow-up period
排除标准
- •Presence of alternate and/or additional liver disease etiologies at Screening, including but not limited to chronic viral hepatitis, autoimmune hepatitis
- •Use of treatments for metabolic syndrome management, including oral antidiabetic drugs (OADs) (e.g., metformin), incretin mimetics (GLP-1 receptor agonists or GLP-1/gastric inhibitory polypeptide [GIP] agonists) or other glucose-lowering agents that has not been stable for at least 6 months prior to Screening
- •Use of Resmetirom that has not been stable for at least 6 months prior to Screening visit
- •Any medical, cognitive, or psychiatric condition that, in the opinion of the Investigator, could contraindicate the use of the investigational drug, make consistent study assessment and follow-up over the 12-month Post-Treatment Follow-up Period unlikely, or would make the participant an unsafe study candidate.
- •Type 1 diabetes, or poorly controlled type 2 diabetes (HbA1c > 8.0% at Screening)
- •History of major trauma to the muscle(s) intended for IM injection meeting any of the following criteria:
- •Within 6 months prior to Screening, or
- •At any timepoint prior to Screening with continued neurologic or musculoskeletal symptoms
- •Prior participation in any systemic experimental treatment or receiving any other systemic investigational treatment including within 6 weeks or 5 half-lives of the active ingredient (whichever is longer) prior to the start of Screening
- •Any vaccination or planned vaccination 30 days prior to dosing, or planned vaccination 8 weeks post dosing
- •Previously received AAV or adenoviral therapy or participation in any previous gene therapy trial
研究组 & 干预措施
Part 1 Cohort 1, dose #1
Dose #1 of VV-14303 will be administered
干预措施: VV-14303 (Genetic)
Part 1 Cohort 2, dose #2
Dose #2 of VV-14303 will be administered
干预措施: VV-14303 (Genetic)
Part 1 Cohort 3, dose #3
Dose #3 of VV-14303 will be administered
干预措施: VV-14303 (Genetic)
Part 2 dose
VV-14303 will be administered at the dose determined from Part 1 (Cohorts 1, 2, and 3)
干预措施: VV-14303 (Genetic)
结局指标
主要结局
Incidence and severity of adverse events, abnormal clinical laboratory values, abnormal physical exams, abnormal vital signs, abnormal ECGs, and abnormal imaging
时间窗: 52 Weeks
Safety of VV-14303 in participants with MASH
Number of participants with improvement in overall metabolic health, as assessed by changes in serum biomarker levels
时间窗: 6 weeks
Evaluate safety and efficacy of VV-14303 in participants with MASH in Part 1
Changes in liver fat content as assessed by Magnetic Resonance Proton Density Fat Fraction (MRI-PDFF) as assessed by FibroScan®
时间窗: 26 Weeks
Efficacy of VV-14303 in participants with MASH in Part 2
Change in liver fat content as assessed by controlled attenuation parameter (CAP) as assessed by FibroScan®
时间窗: 26 weeks
Efficacy of VV-14303 in participants with MASH in Part 2
次要结局
- Efficacy associated with VV-14303 in participants with MASH(Week 26 and 52)
- Efficacy associated with VV-14303 in participants with MASH(52 Weeks)
- Part 1: Efficacy associated with VV-14303 in participants with MASH(26 Weeks)
- Concentration of adeno-associated virus (AAV) vector-mediated transgene product in serum(52 Weeks)