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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1220-7021 | Other Identifier | World Health Organization (WHO) |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A1 DCR-HBVS | Experimental | Single dose, Subcutaneous injection of 0.1mg/kg of DCR-HBVS (HV) |
|
| Cohort A1 Placebo | Placebo Comparator | Single dose, Subcutaneous injection of 0.1mg/kg of Placebo for DCR-HBVS (HV) |
|
| Cohort A2 DCR-HBVS | Experimental | Single dose, Subcutaneous injection of 1.5mg/kg of DCR-HBVS (HV) |
|
| Cohort A2 Placebo | Placebo Comparator | Single dose, Subcutaneous injection of 1.5mg/kg of Placebo for DCR-HBVS (HV) |
|
| Cohort A3 DCR-HBVS | Experimental | Single dose, Subcutaneous injection of 3mg/kg of DCR-HBVS (HV) |
|
| Cohort A3 Placebo | Placebo Comparator | Single dose, Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS (HV) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DCR-HBVS | Drug | DCR-HBVS is a synthetic ribonucleic acid interference (RNAi) drug that consists of a double-stranded oligonucleotide conjugated to N-acetyl-D-galactosamine (GalNAc) ligands. DCR-HBVS is a sterile solution of the siRNA (DCR-S219) at a concentration of 195 mg/mL in water for injection (WFI). |
| Measure | Description | Time Frame |
|---|---|---|
| Number of healthy volunteers with Adverse Events as assessed by CTCAE v5.0 | Number of participants with abnormalities in vital signs, electrocardiogram (ECG), and clinically significant laboratory findings | 4 weeks |
| Number participants with non-cirrhotic chronic Hepatitis B with Adverse Events as assessed by CTCAE v5.0 | Number of participants with abnormalities in vital signs, electrocardiogram (ECG), and clinically significant laboratory findings | 16 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| To characterize the pharmacokinetics of DCR-HBVS in healthy volunteers by monitoring plasma pharmacokinetics profiles of DCR-S219 | Measure the amount of DCR-HBVS excreted in urine | 4 weeks |
| To characterize the pharmacokinetics of DCR-HBVS in healthy volunteers by monitoring through concentrations of DCR-S219 |
| Measure | Description | Time Frame |
|---|---|---|
| To evaluate the preliminary antiviral efficacy of DCR-HBVS in participants with CHB by monitoring changes in serum HBsAg levels (all Group B and C participants)during and after single dose and 12 weeks of treatment with DCR HBVS. | Proportion of participants achieving at least a 1-log reduction in HBsAg AND achieving a HBsAg level < 100 IU/mL at last scheduled visit Time to HBsAg loss (Kaplan-Mayer) Time to anti-HBs seroconversion |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas Bowman, MD | Dicerna Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Monash Health | Clayton | Victoria | 3168 | Australia | ||
| St Vincent's Hospital Melbourne |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37524230 | Derived | Gane EJ, Kim W, Lim TH, Tangkijvanich P, Yoon JH, Sievert W, Sukeepaisarnjaroen W, Thompson AJ, Pavlovic V, Surujbally B, Wat C, Brown BD, Achneck HE, Yuen MF. First-in-human randomized study of RNAi therapeutic RG6346 for chronic hepatitis B virus infection. J Hepatol. 2023 Nov;79(5):1139-1149. doi: 10.1016/j.jhep.2023.07.026. Epub 2023 Jul 29. |
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| ID | Term |
|---|---|
| D019694 | Hepatitis B, Chronic |
| D004266 | DNA Virus Infections |
| D008107 | Liver Diseases |
| ID | Term |
|---|---|
| D006509 | Hepatitis B |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
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Progression from the SAD phase to the first cohort in the MAD phase is contingent upon the Safety Review Committee (SRC) review of a minimum of 14 days post-dose safety and tolerability data from all NHV in at least the first 2 SAD cohorts. The SRC will select one (or more) well-tolerated dose(s) from the SAD phase for administration in the SD and MAD phases. Group B at 3 mg/kg will start in parallel with Group C at the 3 mg/kg dose level. In all study phases, dosing will be staggered with the use of sentinel participants to allow time for the assessment of safety before additional subjects are exposed to study drug. The fixed dosing regimen for Cohorts 4c and 5c was determined following SRC review and assessment of all data up to Cohort 3c. No sentinel dosing will occur in Cohorts 4c and 5c.
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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.
|
| Cohort A4 DCR-HBVS | Experimental | Single dose, Subcutaneous injection of 6mg/kg of DCR-HBVS (HV) |
|
| Cohort A4 Placebo | Placebo Comparator | Single dose, Subcutaneous injection of 6mg/kg of Placebo for DCR-HBVS (HV) |
|
| Cohort A5 DCR-HBVS | Experimental | Single dose, Subcutaneous injection of 12mg/kg of DCR-HBVS (HV) |
|
| Cohort A5 Placebo | Placebo Comparator | Single dose, Subcutaneous injection of 12mg/kg of Placebo for DCR-HBVS (HV) |
|
| Cohort B DCR-HBVS | Experimental | Single dose, Subcutaneous injection of 3mg/kg of for DCR-HBVS (NUC naïve, CHB) |
|
| Cohort B Placebo | Placebo Comparator | Single dose, Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS (NUC naïve, CHB) |
|
| Cohort C1 DCR-HBVS | Experimental | 4 doses- Subcutaneous injection of 1.5mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB) |
|
| Cohort C1 Placebo | Placebo Comparator | 4 doses- Subcutaneous injection of 1.5mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB) |
|
| Cohort C2 DCR-HBVS | Experimental | 4 doses- Subcutaneous injection of 3mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB) |
|
| Cohort C2 Placebo | Placebo Comparator | 4 doses- Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB) |
|
| Cohort C3 DCR-HBVS | Experimental | 4 doses- Subcutaneous injection of 6mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB) |
|
| Cohort C3 Placebo | Placebo Comparator | 4 doses- Subcutaneous injection of 6mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB) |
|
| Cohort 4C DCR-HBVS | Experimental | 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 5C1 DCR-HBVS | Experimental | 4 doses- Subcutaneous injection of 200mg administered every 4 weeks (NUC experienced, CHB) |
|
| Cohort 5C2 DCR-HBVS | Experimental | 2 doses- Subcutaneous injection of 200mg administered every 8 weeks (NUC experienced, CHB) |
|
| Cohort 5C3 DCR-HBVS | Experimental | 2 doses- Subcutaneous injection of 400mg administered every 12 weeks (NUC experienced, CHB) |
|
|
|
| Placebo for DCR-HBVS | Drug | Sterile 9% saline for injection. |
|
|
Measure the amount of DCR-HBVS renal clearance (CLR). |
| 4 weeks |
| To characterize the pharmacokinetics of DCR-HBVS in participants with non-cirrhotic CHB by monitoring plasma pharmacokinetics profiles of DCR-HBVS. | Measure the amount of DCR-HBVS excreted in urine | 12 weeks |
| To characterize the pharmacokinetics of DCR-HBVS in participants with non-cirrhotic CHB by monitoring through concentrations of DCR-HBVS. | Measure DCR-HBVS renal clearance (CLR). | 12 weeks |
| 12 weeks |
| To evaluate the preliminary antiviral efficacy of DCR-HBVS in participants with CHB by monitoring HBeAg levels (HBeAg+ participants only) during and after single dose and 12 weeks of treatment with DCR HBVS. | % of participants with HBeAg loss and anti HBe at last scheduled visit (if HBeAg positive at study entry) | 12 weeks |
| To evaluate the preliminary antiviral efficacy of DCR-HBVS in participants with CHB by monitoring HBV DNA levels (all Group B and C participants) during and after single dose and 12 weeks of treatment with DCR HBVS. | Proportion of participants achieving HBV DNA < 2000 IU/mL (if > 2,000 IU/mL at Baseline); and proportion of participants achieving PCR-nondetectable HBV DNA (if HBV DNA was detectable at Baseline). | 12 weeks |
| To characterize the pharmacodynamics (PD) of DCR-HBVS on plasma levels of HBsAg and HBV in blood. | Track post-treatment duration of any observed efficacy effects. | 12 weeks |
| Fitzroy |
| Victoria |
| 3065 |
| Australia |
| Queen Mary Hospital (The University of Hong Kong) | Hong Kong | Hong Kong |
| Clinical Site | Auckland | 1023 | New Zealand |
| Middlemore Hospital | Auckland | New Zealand |
| Seoul National University Hospital | Seoul | South Korea |
| Seoul Metropolitan Government - Seoul National University Boramae Medical Center | Soeul | South Korea |
| King Culalongkorn Memorial Hospital | Bangkok | Thailand |
| Srinagarind Hospital | Khon Kaen | Thailand |
| D018347 |
| Hepadnaviridae Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006521 | Hepatitis, Chronic |
| D006505 | Hepatitis |
| D004066 | Digestive System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |