Study of Safety and Tolerability of DCR HBVS

NCT03772249 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: DCR-HBVS-101U1111-1220-7021
• Study Type: interventional
• Target: 82
• Locations: 5 countries
• Sites: 9

Brief Summary

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

Conditions

Hepatitis B, Chronic

Keywords

Chronic Hepatitis B; DNA Virus Infections; CHB; HBsAg; Liver Disease; RNAi

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (4)

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

  4 weeks

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

  4 weeks

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

  12 weeks

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

  12 weeks

Other Outcomes (4)

• 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.

  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.

  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.

  12 weeks

Study Arms (22)

Cohort A1 DCR-HBVS

EXPERIMENTAL

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

Drug: DCR-HBVS

Cohort A1 Placebo

PLACEBO COMPARATOR

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

Drug: Placebo for DCR-HBVS

Cohort A2 DCR-HBVS

EXPERIMENTAL

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

Drug: DCR-HBVS

Cohort A2 Placebo

PLACEBO COMPARATOR

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

Drug: Placebo for DCR-HBVS

Cohort A3 DCR-HBVS

EXPERIMENTAL

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

Drug: DCR-HBVS

Cohort A3 Placebo

PLACEBO COMPARATOR

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

Drug: Placebo for DCR-HBVS

Cohort A4 DCR-HBVS

EXPERIMENTAL

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

Drug: DCR-HBVS

Cohort A4 Placebo

PLACEBO COMPARATOR

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

Drug: Placebo for DCR-HBVS

Cohort A5 DCR-HBVS

EXPERIMENTAL

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

Drug: DCR-HBVS

Cohort A5 Placebo

PLACEBO COMPARATOR

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

Drug: Placebo for DCR-HBVS

Cohort B DCR-HBVS

EXPERIMENTAL

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

Drug: DCR-HBVS

Cohort B Placebo

PLACEBO COMPARATOR

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

Drug: Placebo for DCR-HBVS

Cohort C1 DCR-HBVS

EXPERIMENTAL

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

Drug: DCR-HBVS

Cohort C1 Placebo

PLACEBO COMPARATOR

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

Cohort C2 DCR-HBVS

EXPERIMENTAL

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

Drug: DCR-HBVS

Cohort C2 Placebo

PLACEBO COMPARATOR

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

Drug: Placebo for DCR-HBVS

Cohort C3 DCR-HBVS

EXPERIMENTAL

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

Drug: DCR-HBVS

Cohort C3 Placebo

PLACEBO COMPARATOR

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

Drug: Placebo for DCR-HBVS

Cohort 4C DCR-HBVS

EXPERIMENTAL

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

Cohort 5C1 DCR-HBVS

EXPERIMENTAL

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

Drug: DCR-HBVS

Cohort 5C2 DCR-HBVS

EXPERIMENTAL

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

Drug: DCR-HBVS

Cohort 5C3 DCR-HBVS

EXPERIMENTAL

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

Drug: DCR-HBVS

Interventions

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).

Also known as: DCR-S219

Cohort 4C DCR-HBVS; Cohort 5C1 DCR-HBVS; Cohort 5C2 DCR-HBVS; Cohort 5C3 DCR-HBVS; Cohort A1 DCR-HBVS; Cohort A2 DCR-HBVS; Cohort A3 DCR-HBVS; Cohort A4 DCR-HBVS; Cohort A5 DCR-HBVS; Cohort B DCR-HBVS; Cohort C1 DCR-HBVS; Cohort C2 DCR-HBVS; Cohort C3 DCR-HBVS

Placebo for DCR-HBVS DRUG

Sterile 9% saline for injection.

Also known as: Placebo

Cohort A1 Placebo; Cohort A2 Placebo; Cohort A3 Placebo; Cohort A4 Placebo; Cohort A5 Placebo; Cohort B Placebo; Cohort C1 Placebo; Cohort C2 Placebo; Cohort C3 Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy at the time of screening as determined by medical evaluation.
• Capable of giving informed consent.
• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• Dicerna Pharmaceuticals, Inc., a Novo Nordisk company: lead

Study Sites (9)

Monash Health

Clayton, Victoria, 3168, Australia

Location

St Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Queen Mary Hospital (The University of Hong Kong)

Hong Kong, Hong Kong

Location

Clinical Site

Auckland, 1023, New Zealand

Location

Middlemore Hospital

Auckland, New Zealand

Location

Seoul National University Hospital

Seoul, South Korea

Location

Seoul Metropolitan Government - Seoul National University Boramae Medical Center

Soeul, South Korea

Location

King Culalongkorn Memorial Hospital

Bangkok, Thailand

Location

Srinagarind Hospital

Khon Kaen, Thailand

Location

Related Publications (1)

• 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.

  PMID: 37524230 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic; DNA Virus Infections; Liver Diseases

Condition Hierarchy (Ancestors)

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

Study Officials

• Thomas Bowman, MD

  Dicerna Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 3, 2018
• First Posted: December 11, 2018
• Study Start: December 28, 2018
• Primary Completion: July 12, 2022
• Study Completion: July 12, 2022
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

NZ (2); HK (1); KR (2); TH (2); AU (2)