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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
82

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 28, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 12, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 12, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 3, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 10, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 11, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 11, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 10, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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