A Three-Part, Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ALN-PNP siRNA in Participants With Nonalcoholic Fatty Liver Disease (NAFLD) and a PNPLA3 Genetic Risk Factor
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 5
- 主要终点
- Incidence of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
This study is researching an experimental drug called ALN-PNP. This study is focused on participants who are known to have nonalcoholic fatty liver disease (NAFLD), and a specific variant of the patatin-like phospholipase domain containing 3 (PNPLA3) gene.
The aim of this study is to see how safe, tolerable, and effective the study drug is.
This study is looking at several other research questions, including:
- What side effects may happen from taking the study drug
- How the study drug works to change liver fat content in NAFLD
- How much study drug and study drug metabolites (byproduct of the body breaking down the study drug) are in your blood at different times
- Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)
- Better understanding of the study drug and NAFLD
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants from 18 (or country's legal age of adulthood) to 65 years of age, inclusive, at screening visit 1
- •Body mass index (BMI) from 23.0 kg/m^2 to 40.0 kg/m^2, inclusive, for East Asians (including but not limited to South Koreans, Chinese, Taiwanese, and Japanese) and BMI from 27.0 kg/m^2 to 40.0 kg/m^2, inclusive, for any other ethnicity at screening visit 1
- •Meets genotype criteria for the rs738409:G PNPLA3 risk allele: homozygotes (for Part A and Part B) or heterozygotes (optional Part C); p.I148M variant (PNPLA3 rs738409:G [p.I148M]) at screening visit 1
- •Liver fat content ≥8.5% as measured by MRI-PDFF at screening visit 3
- •Generally stable diet (based on participant's recall) for at least 3 months prior to the screening visit
排除标准
- •Evidence of other forms of known chronic liver disease, as defined in the protocol
- •Has a contraindication to MRI examinations, such as persons with cardiac pacemaker and implants made out of metal (for example, cochlear implant, nerve stimulators, magnetic vascular clips, and metallic heart valve), severe claustrophobia, or other contraindications for MRI
- •Is taking a medication to treat a co-morbid condition that is not permitted during the study
- •Has any laboratory parameter assessments at screening, as defined in the protocol
- •History of Type 1 diabetes
- •Bariatric surgery within approximately 5 years prior or planned during the study period
- •Has lost or gained more than 4.0% body weight over the 3 months prior to or during the screening period
- •Has known human immunodeficiency virus (HIV) infection, evidence of current or chronic hepatitis B virus (HBV) infection, or current or chronic hepatitis C virus (HCV) infection, as defined in the protocol
- •Was hospitalized (ie, >24 hours) for any reason within 30 days of the screening visit
- •Note: Other protocol defined Inclusion/Exclusion Criteria apply
研究组 & 干预措施
Part A: Placebo
Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1
干预措施: Placebo (Drug)
Part A: Low Dose
Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1
干预措施: ALN-PNP (Drug)
Part A: Mid Dose
Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1
干预措施: ALN-PNP (Drug)
Part B: High Dose
Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1
干预措施: ALN-PNP (Drug)
Part A: High Dose
Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1
干预措施: ALN-PNP (Drug)
Part B: Placebo
Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1
干预措施: Placebo (Drug)
Part B : Low Dose
Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1
干预措施: ALN-PNP (Drug)
Part B: Mid Dose
Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1
干预措施: ALN-PNP (Drug)
Part C: Placebo (Optional)
Sponsor may elect to enroll participants who are heterozygous for the PNPLA3 rs738409:G risk allele and may be randomized 1:1
干预措施: Placebo (Drug)
Part C: High Dose (Optional)
Sponsor may elect to enroll participants who are heterozygous for the PNPLA3 rs738409:G risk allele and may be randomized 1:1
干预措施: ALN-PNP (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events (TEAEs)
时间窗: Up to 253 days
Severity of TEAEs
时间窗: Up to 253 days
次要结局
- Change in liver fat fraction by magnetic resonance imaging proton density fat fraction (MRI-PDFF) in participants with NAFLD(Baseline up to 253 days)
- Change in lipoprotein a (Lp(a)) in participants with NAFLD(Baseline up to 253 days)
- Change in low-density lipoprotein cholesterol (LDL-C) in participants with NAFLD(Baseline up to 253 days)
- Change in high-density lipoprotein cholesterol (HDL-C) in participants with NAFLD(Baseline up to 253 days)
- Change in triglycerides (TG) in participants with NAFLD(Baseline up to 253 days)
- Change in apolipoprotein B (ApoB) in participants with NAFLD(Baseline up to 253 days)
- Concentration of ALN-PNP and potential major metabolite(s) in plasma over time(Up to 253 days)
- Change in apolipoprotein A1 (ApoA1) in participants with NAFLD(Baseline up to 253 days)
- Incidence of anti-drug antibodies (ADAs) to ALN-PNP(Up to 253 days)
- Titer of anti-drug antibodies (ADAs) to ALN-PNP(Up to 253 days)