Study of Safety and Tolerability of DCR HBVS

July 10, 2024 updated by: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

82

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Monash Health
      • Fitzroy, Victoria, Australia, 3065
        • St Vincent's Hospital Melbourne
  • Hong Kong
      • Hong Kong, Hong Kong
        • Queen Mary Hospital (The University of Hong Kong)
  • Korea, Republic of
      • Seoul, Korea, Republic of
        • Seoul National University Hospital
      • Soeul, Korea, Republic of
        • Seoul Metropolitan Government - Seoul National University Boramae Medical Center
  • New Zealand
      • Auckland, New Zealand
        • Middlemore Hospital
      • Auckland, New Zealand, 1023
        • Clinical Site
  • Thailand
      • Bangkok, Thailand
        • King Culalongkorn Memorial Hospital
      • Khon Kaen, Thailand
        • Srinagarind Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort A1 DCR-HBVS
Single dose, Subcutaneous injection of 0.1mg/kg of DCR-HBVS (HV)
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).
Other Names:
  • DCR-S219
Placebo Comparator: Cohort A1 Placebo
Single dose, Subcutaneous injection of 0.1mg/kg of Placebo for DCR-HBVS (HV)
Drug: Placebo for DCR-HBVS
Sterile 9% saline for injection.
Other Names:
  • Placebo
Experimental: Cohort A2 DCR-HBVS
Single dose, Subcutaneous injection of 1.5mg/kg of DCR-HBVS (HV)
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).
Other Names:
  • DCR-S219
Placebo Comparator: Cohort A2 Placebo
Single dose, Subcutaneous injection of 1.5mg/kg of Placebo for DCR-HBVS (HV)
Drug: Placebo for DCR-HBVS
Sterile 9% saline for injection.
Other Names:
  • Placebo
Experimental: Cohort A3 DCR-HBVS
Single dose, Subcutaneous injection of 3mg/kg of DCR-HBVS (HV)
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).
Other Names:
  • DCR-S219
Placebo Comparator: Cohort A3 Placebo
Single dose, Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS (HV)
Drug: Placebo for DCR-HBVS
Sterile 9% saline for injection.
Other Names:
  • Placebo
Experimental: Cohort A4 DCR-HBVS
Single dose, Subcutaneous injection of 6mg/kg of DCR-HBVS (HV)
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).
Other Names:
  • DCR-S219
Placebo Comparator: Cohort A4 Placebo
Single dose, Subcutaneous injection of 6mg/kg of Placebo for DCR-HBVS (HV)
Drug: Placebo for DCR-HBVS
Sterile 9% saline for injection.
Other Names:
  • Placebo
Experimental: Cohort A5 DCR-HBVS
Single dose, Subcutaneous injection of 12mg/kg of DCR-HBVS (HV)
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).
Other Names:
  • DCR-S219
Placebo Comparator: Cohort A5 Placebo
Single dose, Subcutaneous injection of 12mg/kg of Placebo for DCR-HBVS (HV)
Drug: Placebo for DCR-HBVS
Sterile 9% saline for injection.
Other Names:
  • Placebo
Experimental: Cohort B DCR-HBVS
Single dose, Subcutaneous injection of 3mg/kg of for DCR-HBVS (NUC naïve, CHB)
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).
Other Names:
  • DCR-S219
Placebo Comparator: Cohort B Placebo
Single dose, Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS (NUC naïve, CHB)
Drug: Placebo for DCR-HBVS
Sterile 9% saline for injection.
Other Names:
  • Placebo
Experimental: Cohort C1 DCR-HBVS
4 doses- Subcutaneous injection of 1.5mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB)
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).
Other Names:
  • DCR-S219
Placebo Comparator: Cohort C1 Placebo
4 doses- Subcutaneous injection of 1.5mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB)
Drug: Placebo for DCR-HBVS
Sterile 9% saline for injection.
Other Names:
  • Placebo
Experimental: Cohort C2 DCR-HBVS
4 doses- Subcutaneous injection of 3mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB)
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).
Other Names:
  • DCR-S219
Placebo Comparator: Cohort C2 Placebo
4 doses- Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB)
Drug: Placebo for DCR-HBVS
Sterile 9% saline for injection.
Other Names:
  • Placebo
Experimental: Cohort C3 DCR-HBVS
4 doses- Subcutaneous injection of 6mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB)
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).
Other Names:
  • DCR-S219
Placebo Comparator: Cohort C3 Placebo
4 doses- Subcutaneous injection of 6mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB)
Drug: Placebo for DCR-HBVS
Sterile 9% saline for injection.
Other Names:
  • Placebo
Experimental: Cohort 4C 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)
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).
Other Names:
  • DCR-S219
Experimental: Cohort 5C1 DCR-HBVS
4 doses- Subcutaneous injection of 200mg administered every 4 weeks (NUC experienced, CHB)
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).
Other Names:
  • DCR-S219
Experimental: Cohort 5C2 DCR-HBVS
2 doses- Subcutaneous injection of 200mg administered every 8 weeks (NUC experienced, CHB)
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).
Other Names:
  • DCR-S219
Experimental: Cohort 5C3 DCR-HBVS
2 doses- Subcutaneous injection of 400mg administered every 12 weeks (NUC experienced, CHB)
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).
Other Names:
  • DCR-S219

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
4 weeks
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
16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
4 weeks
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).
4 weeks
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
12 weeks
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).
12 weeks

Other Outcome Measures

Outcome Measure
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.
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
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.
Time Frame: 12 weeks
% 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.
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).
12 weeks
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.
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Investigators

  • Study Director: Thomas Bowman, MD, Dicerna Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 28, 2018

Primary Completion (Actual)

July 12, 2022

Study Completion (Actual)

July 12, 2022

Study Registration Dates

First Submitted

December 3, 2018

First Submitted That Met QC Criteria

December 10, 2018

First Posted (Actual)

December 11, 2018

Study Record Updates

Last Update Posted (Actual)

July 11, 2024

Last Update Submitted That Met QC Criteria

July 10, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DCR-HBVS-101
  • U1111-1220-7021 (Other Identifier: World Health Organization (WHO))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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