Study of Safety and Tolerability of DCR HBVS
- Registration Number
- NCT03772249
- Lead Sponsor
- Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
- Brief Summary
DCR-HBVS will be evaluated for safety and efficacy in healthy volunteers and chronic hepatitis B patients.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 82
- 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).
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort A1 Placebo Placebo for DCR-HBVS Single dose, Subcutaneous injection of 0.1mg/kg of Placebo for DCR-HBVS (HV) Cohort A3 Placebo Placebo for DCR-HBVS Single dose, Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS (HV) Cohort A1 DCR-HBVS DCR-HBVS Single dose, Subcutaneous injection of 0.1mg/kg of DCR-HBVS (HV) Cohort A2 Placebo Placebo for DCR-HBVS Single dose, Subcutaneous injection of 1.5mg/kg of Placebo for DCR-HBVS (HV) Cohort A3 DCR-HBVS DCR-HBVS Single dose, Subcutaneous injection of 3mg/kg of DCR-HBVS (HV) Cohort A4 DCR-HBVS DCR-HBVS Single dose, Subcutaneous injection of 6mg/kg of DCR-HBVS (HV) Cohort A4 Placebo Placebo for DCR-HBVS Single dose, Subcutaneous injection of 6mg/kg of Placebo for DCR-HBVS (HV) Cohort 4C DCR-HBVS 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) Cohort A2 DCR-HBVS DCR-HBVS Single dose, Subcutaneous injection of 1.5mg/kg of DCR-HBVS (HV) Cohort A5 Placebo Placebo for DCR-HBVS Single dose, Subcutaneous injection of 12mg/kg of Placebo for DCR-HBVS (HV) Cohort B DCR-HBVS DCR-HBVS Single dose, Subcutaneous injection of 3mg/kg of for DCR-HBVS (NUC naïve, CHB) Cohort C1 DCR-HBVS DCR-HBVS 4 doses- Subcutaneous injection of 1.5mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB) Cohort B Placebo Placebo for DCR-HBVS Single dose, Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS (NUC naïve, CHB) Cohort 5C1 DCR-HBVS DCR-HBVS 4 doses- Subcutaneous injection of 200mg administered every 4 weeks (NUC experienced, CHB) Cohort C2 Placebo Placebo for DCR-HBVS 4 doses- Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB) Cohort C3 Placebo Placebo for DCR-HBVS 4 doses- Subcutaneous injection of 6mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB) Cohort C1 Placebo Placebo for DCR-HBVS 4 doses- Subcutaneous injection of 1.5mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB) Cohort C2 DCR-HBVS DCR-HBVS 4 doses- Subcutaneous injection of 3mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB) Cohort 5C3 DCR-HBVS DCR-HBVS 2 doses- Subcutaneous injection of 400mg administered every 12 weeks (NUC experienced, CHB) Cohort A5 DCR-HBVS DCR-HBVS Single dose, Subcutaneous injection of 12mg/kg of DCR-HBVS (HV) Cohort C3 DCR-HBVS DCR-HBVS 4 doses- Subcutaneous injection of 6mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB) Cohort 5C2 DCR-HBVS DCR-HBVS 2 doses- Subcutaneous injection of 200mg administered every 8 weeks (NUC experienced, CHB)
- Primary Outcome Measures
Name Time Method Number of healthy volunteers with Adverse Events as assessed by CTCAE v5.0 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 16 weeks Number of participants with abnormalities in vital signs, electrocardiogram (ECG), and clinically significant laboratory findings
- Secondary Outcome Measures
Name Time Method To characterize the pharmacokinetics of DCR-HBVS in healthy volunteers by monitoring plasma pharmacokinetics profiles of DCR-S219 4 weeks Measure the amount of DCR-HBVS excreted in urine
To characterize the pharmacokinetics of DCR-HBVS in participants with non-cirrhotic CHB by monitoring plasma pharmacokinetics profiles of DCR-HBVS. 12 weeks Measure the amount of DCR-HBVS excreted in urine
To characterize the pharmacokinetics of DCR-HBVS in participants with non-cirrhotic CHB by monitoring through concentrations of DCR-HBVS. 12 weeks Measure DCR-HBVS renal clearance (CLR).
To characterize the pharmacokinetics of DCR-HBVS in healthy volunteers by monitoring through concentrations of DCR-S219 4 weeks Measure the amount of DCR-HBVS renal clearance (CLR).
Trial Locations
- Locations (9)
Clinical Site
🇳🇿Auckland, New Zealand
King Culalongkorn Memorial Hospital
🇹🇭Bangkok, Thailand
Srinagarind Hospital
🇹🇭Khon Kaen, Thailand
Monash Health
🇦🇺Clayton, Victoria, Australia
Queen Mary Hospital (The University of Hong Kong)
🇭🇰Hong Kong, Hong Kong
St Vincent's Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Seoul Metropolitan Government - Seoul National University Boramae Medical Center
🇰🇷Soeul, Korea, Republic of
Middlemore Hospital
🇳🇿Auckland, New Zealand