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Study of Safety and Tolerability of DCR HBVS

NCT ID: NCT03772249

Last Updated: 2024-09-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

82 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-12-28

Study Completion Date

2022-07-12

Brief Summary

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

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Detailed Description

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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.

Conditions

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Hepatitis B, Chronic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
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.

Study Groups

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Cohort A1 DCR-HBVS

Single dose, Subcutaneous injection of 0.1mg/kg of DCR-HBVS (HV)

Group Type EXPERIMENTAL

DCR-HBVS

Intervention Type 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).

Cohort A1 Placebo

Single dose, Subcutaneous injection of 0.1mg/kg of Placebo for DCR-HBVS (HV)

Group Type PLACEBO_COMPARATOR

Placebo for DCR-HBVS

Intervention Type DRUG

Sterile 9% saline for injection.

Cohort A2 DCR-HBVS

Single dose, Subcutaneous injection of 1.5mg/kg of DCR-HBVS (HV)

Group Type EXPERIMENTAL

DCR-HBVS

Intervention Type 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).

Cohort A2 Placebo

Single dose, Subcutaneous injection of 1.5mg/kg of Placebo for DCR-HBVS (HV)

Group Type PLACEBO_COMPARATOR

Placebo for DCR-HBVS

Intervention Type DRUG

Sterile 9% saline for injection.

Cohort A3 DCR-HBVS

Single dose, Subcutaneous injection of 3mg/kg of DCR-HBVS (HV)

Group Type EXPERIMENTAL

DCR-HBVS

Intervention Type 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).

Cohort A3 Placebo

Single dose, Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS (HV)

Group Type PLACEBO_COMPARATOR

Placebo for DCR-HBVS

Intervention Type DRUG

Sterile 9% saline for injection.

Cohort A4 DCR-HBVS

Single dose, Subcutaneous injection of 6mg/kg of DCR-HBVS (HV)

Group Type EXPERIMENTAL

DCR-HBVS

Intervention Type 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).

Cohort A4 Placebo

Single dose, Subcutaneous injection of 6mg/kg of Placebo for DCR-HBVS (HV)

Group Type PLACEBO_COMPARATOR

Placebo for DCR-HBVS

Intervention Type DRUG

Sterile 9% saline for injection.

Cohort A5 DCR-HBVS

Single dose, Subcutaneous injection of 12mg/kg of DCR-HBVS (HV)

Group Type EXPERIMENTAL

DCR-HBVS

Intervention Type 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).

Cohort A5 Placebo

Single dose, Subcutaneous injection of 12mg/kg of Placebo for DCR-HBVS (HV)

Group Type PLACEBO_COMPARATOR

Placebo for DCR-HBVS

Intervention Type DRUG

Sterile 9% saline for injection.

Cohort B DCR-HBVS

Single dose, Subcutaneous injection of 3mg/kg of for DCR-HBVS (NUC naïve, CHB)

Group Type EXPERIMENTAL

DCR-HBVS

Intervention Type 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).

Cohort B Placebo

Single dose, Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS (NUC naïve, CHB)

Group Type PLACEBO_COMPARATOR

Placebo for DCR-HBVS

Intervention Type DRUG

Sterile 9% saline for injection.

Cohort C1 DCR-HBVS

4 doses- Subcutaneous injection of 1.5mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB)

Group Type EXPERIMENTAL

DCR-HBVS

Intervention Type 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).

Cohort C1 Placebo

4 doses- Subcutaneous injection of 1.5mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB)

Group Type PLACEBO_COMPARATOR

Placebo for DCR-HBVS

Intervention Type DRUG

Sterile 9% saline for injection.

Cohort C2 DCR-HBVS

4 doses- Subcutaneous injection of 3mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB)

Group Type EXPERIMENTAL

DCR-HBVS

Intervention Type 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).

Cohort C2 Placebo

4 doses- Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB)

Group Type PLACEBO_COMPARATOR

Placebo for DCR-HBVS

Intervention Type DRUG

Sterile 9% saline for injection.

Cohort C3 DCR-HBVS

4 doses- Subcutaneous injection of 6mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB)

Group Type EXPERIMENTAL

DCR-HBVS

Intervention Type 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).

Cohort C3 Placebo

4 doses- Subcutaneous injection of 6mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB)

Group Type PLACEBO_COMPARATOR

Placebo for DCR-HBVS

Intervention Type DRUG

Sterile 9% saline for injection.

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)

Group Type EXPERIMENTAL

DCR-HBVS

Intervention Type 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).

Cohort 5C1 DCR-HBVS

4 doses- Subcutaneous injection of 200mg administered every 4 weeks (NUC experienced, CHB)

Group Type EXPERIMENTAL

DCR-HBVS

Intervention Type 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).

Cohort 5C2 DCR-HBVS

2 doses- Subcutaneous injection of 200mg administered every 8 weeks (NUC experienced, CHB)

Group Type EXPERIMENTAL

DCR-HBVS

Intervention Type 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).

Cohort 5C3 DCR-HBVS

2 doses- Subcutaneous injection of 400mg administered every 12 weeks (NUC experienced, CHB)

Group Type EXPERIMENTAL

DCR-HBVS

Intervention Type 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).

Interventions

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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).

Intervention Type DRUG

Placebo for DCR-HBVS

Sterile 9% saline for injection.

Intervention Type DRUG

Other Intervention Names

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DCR-S219 Placebo

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thomas Bowman, MD

Role: STUDY_DIRECTOR

Dicerna Pharmaceuticals

Locations

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Monash Health

Clayton, Victoria, Australia

Site Status

St Vincent's Hospital Melbourne

Fitzroy, Victoria, Australia

Site Status

Queen Mary Hospital (The University of Hong Kong)

Hong Kong, , Hong Kong

Site Status

Clinical Site

Auckland, , New Zealand

Site Status

Middlemore Hospital

Auckland, , New Zealand

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Seoul Metropolitan Government - Seoul National University Boramae Medical Center

Soeul, , South Korea

Site Status

King Culalongkorn Memorial Hospital

Bangkok, , Thailand

Site Status

Srinagarind Hospital

Khon Kaen, , Thailand

Site Status

Countries

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Australia Hong Kong New Zealand South Korea Thailand

References

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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.

Reference Type DERIVED
PMID: 37524230 (View on PubMed)

Other Identifiers

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U1111-1220-7021

Identifier Type: OTHER

Identifier Source: secondary_id

DCR-HBVS-101

Identifier Type: -

Identifier Source: org_study_id

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