Study of Safety and Tolerability of DCR HBVS

A Three-Part, Phase 1, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of DCR-HBVS in Healthy Volunteers and Patients With Chronic Hepatitis B

DCR-HBVS will be evaluated for safety and efficacy in healthy volunteers and chronic hepatitis B patients.

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.

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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).