A Three-Part, Phase 1, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of DCR-HBVS in Healthy Volunteers and Patients With Chronic Hepatitis B
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 82
- 试验地点
- 9
- 主要终点
- Number of healthy volunteers with Adverse Events as assessed by CTCAE v5.0
研究概览
简要总结
DCR-HBVS will be evaluated for safety and efficacy in healthy volunteers and chronic hepatitis B patients.
详细描述
DCR HBVS is being developed for the treatment of chronic hepatitis B (CHB) in adults. The study will be conducted in 3 parts, a single ascending-dose (SAD) phase in normal healthy volunteers (Group A), a single-dose (SD) phase in patients with CHB (Group B), and a multiple ascending-dose (MAD) phase in patients with CHB (Group 1c-3c). Cohort 4c is a single ascending dose with a possible duration of up to 48 weeks. Cohort 5c is a multiple dose cohort with a possible duration of up to 72 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
This is a double-blind study in which the study site team, the Sponsor, and the participants will be blinded to treatment assignment. The unblinded pharmacist will cover each syringe, prior to transport to the bedside, to ensure blinding. The drug will be injected by an unblinded nurse or physician who is not part of the study team. Participants will be centrally assigned to randomized study intervention using an Interactive Voice/Web Response System (IVRS/IWRS). Cohorts 4c and 5c will be open label.
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
- 是
入选标准
- •Healthy at the time of screening as determined by medical evaluation.
- •Capable of giving informed consent.
- •12-lead ECG within normal limits or with no clinically significant abnormalities.
- •Negative screen for alcohol or drugs of abuse.
- •Non-smokers for at least 3 months with a negative urinary cotinine concentration at screening.
- •BMI within range 18.0 - 32.0 kg/m2 (inclusive).
- •Female participants not pregnant, not breastfeeding, and not of childbearing potential or willing to follow contraceptive guidance.
- •Chronic hepatitis B infection (Group B and C only).
- •Clinical history compatible with compensated liver disease with no evidence of cirrhosis (Group B and C only).
- •Continuously on nucleotides (NUC) therapy for at least 12 weeks prior to screening (Group C only).
排除标准
- •History of any medical condition that may interfere with the absorption, distribution, or elimination of study drug.
- •Poorly controlled or unstable hypertension.
- •History of diabetes mellitus treated with insulin or hypoglycemic agents.
- •History of asthma requiring hospital admission within the preceding 12 months.
- •Evidence of G-6-PD deficiency.
- •Currently poorly controlled endocrine conditions, excluding thyroid conditions.
- •History of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc.
- •Clinically relevant surgical history.
- •Use of prescription medications (excluding contraception for women) within 4 weeks prior to the administration of study intervention.
- •Use of clinically relevant over-the-counter medication or supplements (excluding routine vitamins) within 7 days of first dosing.
- •Has received an investigational agent within the 3 months prior to dosing or is in follow-up of another study.
- •Antiviral therapy (other than entecavir or tenofovir) within 3 months of screening or treatment with interferon in the last 3 years (Group B and C only).
- •Use within the last 6 months of anticoagulants or systemically administered corticosteroids, immunomodulators, or immunosuppressants (Group B and C only).
研究组 & 干预措施
Cohort A1 DCR-HBVS
Single dose, Subcutaneous injection of 0.1mg/kg of DCR-HBVS (HV)
干预措施: DCR-HBVS (Drug)
Cohort A1 Placebo
Single dose, Subcutaneous injection of 0.1mg/kg of Placebo for DCR-HBVS (HV)
干预措施: Placebo for DCR-HBVS (Drug)
Cohort A2 DCR-HBVS
Single dose, Subcutaneous injection of 1.5mg/kg of DCR-HBVS (HV)
干预措施: DCR-HBVS (Drug)
Cohort A2 Placebo
Single dose, Subcutaneous injection of 1.5mg/kg of Placebo for DCR-HBVS (HV)
干预措施: Placebo for DCR-HBVS (Drug)
Cohort A3 DCR-HBVS
Single dose, Subcutaneous injection of 3mg/kg of DCR-HBVS (HV)
干预措施: DCR-HBVS (Drug)
Cohort A3 Placebo
Single dose, Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS (HV)
干预措施: Placebo for DCR-HBVS (Drug)
Cohort A4 DCR-HBVS
Single dose, Subcutaneous injection of 6mg/kg of DCR-HBVS (HV)
干预措施: DCR-HBVS (Drug)
Cohort A4 Placebo
Single dose, Subcutaneous injection of 6mg/kg of Placebo for DCR-HBVS (HV)
干预措施: Placebo for DCR-HBVS (Drug)
Cohort A5 DCR-HBVS
Single dose, Subcutaneous injection of 12mg/kg of DCR-HBVS (HV)
干预措施: DCR-HBVS (Drug)
Cohort A5 Placebo
Single dose, Subcutaneous injection of 12mg/kg of Placebo for DCR-HBVS (HV)
干预措施: Placebo for DCR-HBVS (Drug)
Cohort B DCR-HBVS
Single dose, Subcutaneous injection of 3mg/kg of for DCR-HBVS (NUC naïve, CHB)
干预措施: DCR-HBVS (Drug)
Cohort B Placebo
Single dose, Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS (NUC naïve, CHB)
干预措施: Placebo for DCR-HBVS (Drug)
Cohort C1 DCR-HBVS
4 doses- Subcutaneous injection of 1.5mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB)
干预措施: DCR-HBVS (Drug)
Cohort C1 Placebo
4 doses- Subcutaneous injection of 1.5mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB)
干预措施: Placebo for DCR-HBVS (Drug)
Cohort C2 DCR-HBVS
4 doses- Subcutaneous injection of 3mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB)
干预措施: DCR-HBVS (Drug)
Cohort C2 Placebo
4 doses- Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB)
干预措施: Placebo for DCR-HBVS (Drug)
Cohort C3 DCR-HBVS
4 doses- Subcutaneous injection of 6mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB)
干预措施: DCR-HBVS (Drug)
Cohort C3 Placebo
4 doses- Subcutaneous injection of 6mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB)
干预措施: Placebo for DCR-HBVS (Drug)
Cohort 4C DCR-HBVS
1 dose- Subcutaneous injection of 100mg (NUC experienced, CHB)
1 dose- Subcutaneous injection of 200mg (NUC experienced, CHB)
1 dose- Subcutaneous injection of 400mg (NUC experienced, CHB)
干预措施: DCR-HBVS (Drug)
Cohort 5C1 DCR-HBVS
4 doses- Subcutaneous injection of 200mg administered every 4 weeks (NUC experienced, CHB)
干预措施: DCR-HBVS (Drug)
Cohort 5C2 DCR-HBVS
2 doses- Subcutaneous injection of 200mg administered every 8 weeks (NUC experienced, CHB)
干预措施: DCR-HBVS (Drug)
Cohort 5C3 DCR-HBVS
2 doses- Subcutaneous injection of 400mg administered every 12 weeks (NUC experienced, CHB)
干预措施: DCR-HBVS (Drug)
结局指标
主要结局
Number of healthy volunteers with Adverse Events as assessed by CTCAE v5.0
时间窗: 4 weeks
Number of participants with abnormalities in vital signs, electrocardiogram (ECG), and clinically significant laboratory findings
Number participants with non-cirrhotic chronic Hepatitis B with Adverse Events as assessed by CTCAE v5.0
时间窗: 16 weeks
Number of participants with abnormalities in vital signs, electrocardiogram (ECG), and clinically significant laboratory findings
次要结局
- To characterize the pharmacokinetics of DCR-HBVS in healthy volunteers by monitoring plasma pharmacokinetics profiles of DCR-S219(4 weeks)
- To characterize the pharmacokinetics of DCR-HBVS in participants with non-cirrhotic CHB by monitoring plasma pharmacokinetics profiles of DCR-HBVS.(12 weeks)
- To characterize the pharmacokinetics of DCR-HBVS in participants with non-cirrhotic CHB by monitoring through concentrations of DCR-HBVS.(12 weeks)
- To characterize the pharmacokinetics of DCR-HBVS in healthy volunteers by monitoring through concentrations of DCR-S219(4 weeks)