Study of Safety and Tolerability of DCR HBVS

Hepatitis B, Chronic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03772249
• Other study ID #: DCR-HBVS-101
• Secondary ID: U1111-1220-7021
• Status: Completed
• Phase: Phase 1
• Start date: December 28, 2018
• Est. completion date: July 12, 2022

Study information

• Verified date: September 2022
• Source: Dicerna Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: July 12, 2022
• Est. primary completion date: July 12, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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).

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Drug:
• DCR-HBVS
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).
• Placebo for DCR-HBVS
Sterile 9% saline for injection.

Locations

Country	Name	City	State
Australia	Monash Health	Clayton	Victoria
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria
Hong Kong	Queen Mary Hospital (The University of Hong Kong)	Hong Kong
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul Metropolitan Government - Seoul National University Boramae Medical Center	Soeul
New Zealand	Clinical Site	Auckland
New Zealand	Middlemore Hospital	Auckland
Thailand	King Culalongkorn Memorial Hospital	Bangkok
Thailand	Srinagarind Hospital	Khon Kaen

Sponsors (1)

Lead Sponsor	Collaborator
Dicerna Pharmaceuticals, Inc.

Countries where clinical trial is conducted

Australia,  Hong Kong,  Korea, Republic of,  New Zealand,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	12 weeks
Other	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
Other	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
Other	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
Primary	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
Primary	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
Secondary	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
Secondary	To characterize the pharmacokinetics of DCR-HBVS in healthy volunteers by monitoring through concentrations of DCR-S219	Measure the amount of DCR-HBVS renal clearance (CLR).	4 weeks
Secondary	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
Secondary	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