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Completed

NCT Number: NCT03772249

Study of Safety and Tolerability of DCR HBVS

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

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Key information

Conditions

Hepatitis B, Chronic Blood-Borne Infections Chronic Disease Communicable Diseases DNA Virus Infections Digestive System Diseases Disease Attributes Hepadnaviridae Infections Hepatitis Hepatitis B Hepatitis, Chronic Hepatitis, Viral, Human Infections Liver Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Virus Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Monash Health, Clayton, Victoria, Australia

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

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).

Other names: DCR-S219

Placebo for DCR-HBVS

Drug

Sterile 9% saline for injection.

Other names: Placebo

Primary outcomes

  1. Number of healthy volunteers with Adverse Events as assessed by CTCAE v5.0

    Time frame: 4 weeks

    Number of participants with abnormalities in vital signs, electrocardiogram (ECG), and clinically significant laboratory findings

  2. Number participants with non-cirrhotic chronic Hepatitis B with Adverse Events as assessed by CTCAE v5.0

    Time frame: 16 weeks

    Number of participants with abnormalities in vital signs, electrocardiogram (ECG), and clinically significant laboratory findings

Secondary outcomes

  1. To characterize the pharmacokinetics of DCR-HBVS in healthy volunteers by monitoring plasma pharmacokinetics profiles of DCR-S219

    Time frame: 4 weeks

    Measure the amount of DCR-HBVS excreted in urine

  2. To characterize the pharmacokinetics of DCR-HBVS in healthy volunteers by monitoring through concentrations of DCR-S219

    Time frame: 4 weeks

    Measure the amount of DCR-HBVS renal clearance (CLR).

  3. To characterize the pharmacokinetics of DCR-HBVS in participants with non-cirrhotic CHB by monitoring plasma pharmacokinetics profiles of DCR-HBVS.

    Time frame: 12 weeks

    Measure the amount of DCR-HBVS excreted in urine

  4. To characterize the pharmacokinetics of DCR-HBVS in participants with non-cirrhotic CHB by monitoring through concentrations of DCR-HBVS.

    Time frame: 12 weeks

    Measure DCR-HBVS renal clearance (CLR).

Other outcomes

  1. 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.

    Time frame: 12 weeks

    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

  2. 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.

    Time frame: 12 weeks

    % of participants with HBeAg loss and anti HBe at last scheduled visit (if HBeAg positive at study entry)

  3. 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.

    Time frame: 12 weeks

    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).

  4. To characterize the pharmacodynamics (PD) of DCR-HBVS on plasma levels of HBsAg and HBV in blood.

    Time frame: 12 weeks

    Track post-treatment duration of any observed efficacy effects.

Sponsors and collaborators

Lead sponsor

Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Industry

Registry information

Official study title

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

Important dates

Study start
2018
Primary completion
2022
Study completion
2022
First posted
Dec 11, 2018
Registry last updated
Sep 19, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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