Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03772249




Registration number
NCT03772249
Ethics application status
Date submitted
3/12/2018
Date registered
11/12/2018
Date last updated
30/09/2022

Titles & IDs
Public title
Study of Safety and Tolerability of DCR HBVS
Scientific title
A Three-Part, Phase 1, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of DCR-HBVS in Healthy Volunteers and Patients With Chronic Hepatitis B
Secondary ID [1] 0 0
U1111-1220-7021
Secondary ID [2] 0 0
DCR-HBVS-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B, Chronic 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - DCR-HBVS
Treatment: Drugs - Placebo for DCR-HBVS

Experimental: Cohort A1 DCR-HBVS - Single dose, Subcutaneous injection of 0.1mg/kg of DCR-HBVS (HV)

Placebo Comparator: Cohort A1 Placebo - Single dose, Subcutaneous injection of 0.1mg/kg of Placebo for DCR-HBVS (HV)

Experimental: Cohort A2 DCR-HBVS - Single dose, Subcutaneous injection of 1.5mg/kg of DCR-HBVS (HV)

Placebo Comparator: Cohort A2 Placebo - Single dose, Subcutaneous injection of 1.5mg/kg of Placebo for DCR-HBVS (HV)

Experimental: Cohort A3 DCR-HBVS - Single dose, Subcutaneous injection of 3mg/kg of DCR-HBVS (HV)

Placebo Comparator: Cohort A3 Placebo - Single dose, Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS (HV)

Experimental: Cohort A4 DCR-HBVS - Single dose, Subcutaneous injection of 6mg/kg of DCR-HBVS (HV)

Placebo Comparator: Cohort A4 Placebo - Single dose, Subcutaneous injection of 6mg/kg of Placebo for DCR-HBVS (HV)

Experimental: Cohort A5 DCR-HBVS - Single dose, Subcutaneous injection of 12mg/kg of DCR-HBVS (HV)

Placebo Comparator: Cohort A5 Placebo - Single dose, Subcutaneous injection of 12mg/kg of Placebo for DCR-HBVS (HV)

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

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

Experimental: Cohort C1 DCR-HBVS - 4 doses- Subcutaneous injection of 1.5mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB)

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)

Experimental: Cohort C2 DCR-HBVS - 4 doses- Subcutaneous injection of 3mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB)

Placebo Comparator: Cohort C2 Placebo - 4 doses- Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB)

Experimental: Cohort C3 DCR-HBVS - 4 doses- Subcutaneous injection of 6mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB)

Placebo Comparator: Cohort C3 Placebo - 4 doses- Subcutaneous injection of 6mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB)

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)

Experimental: Cohort 5C1 DCR-HBVS - 4 doses- Subcutaneous injection of 200mg administered every 4 weeks (NUC experienced, CHB)

Experimental: Cohort 5C2 DCR-HBVS - 2 doses- Subcutaneous injection of 200mg administered every 8 weeks (NUC experienced, CHB)

Experimental: Cohort 5C3 DCR-HBVS - 2 doses- Subcutaneous injection of 400mg administered every 12 weeks (NUC experienced, CHB)


Treatment: Drugs: 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).

Treatment: Drugs: Placebo for DCR-HBVS
Sterile 9% saline for injection.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of healthy volunteers with Adverse Events as assessed by CTCAE v5.0
Timepoint [1] 0 0
4 weeks
Primary outcome [2] 0 0
Number participants with non-cirrhotic chronic Hepatitis B with Adverse Events as assessed by CTCAE v5.0
Timepoint [2] 0 0
16 weeks
Secondary outcome [1] 0 0
To characterize the pharmacokinetics of DCR-HBVS in healthy volunteers by monitoring plasma pharmacokinetics profiles of DCR-S219
Timepoint [1] 0 0
4 weeks
Secondary outcome [2] 0 0
To characterize the pharmacokinetics of DCR-HBVS in healthy volunteers by monitoring through concentrations of DCR-S219
Timepoint [2] 0 0
4 weeks
Secondary outcome [3] 0 0
To characterize the pharmacokinetics of DCR-HBVS in participants with non-cirrhotic CHB by monitoring plasma pharmacokinetics profiles of DCR-HBVS.
Timepoint [3] 0 0
12 weeks
Secondary outcome [4] 0 0
To characterize the pharmacokinetics of DCR-HBVS in participants with non-cirrhotic CHB by monitoring through concentrations of DCR-HBVS.
Timepoint [4] 0 0
12 weeks

Eligibility
Key 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).
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/12/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
12/07/2022
Sample size
Target
Accrual to date
Final
82
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Monash Health - Clayton
Recruitment hospital [2] 0 0
St Vincent's Hospital Melbourne - Fitzroy
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
Hong Kong
State/province [1] 0 0
Hong Kong
Country [2] 0 0
Korea, Republic of
State/province [2] 0 0
Seoul
Country [3] 0 0
Korea, Republic of
State/province [3] 0 0
Soeul
Country [4] 0 0
New Zealand
State/province [4] 0 0
Auckland
Country [5] 0 0
Thailand
State/province [5] 0 0
Bangkok
Country [6] 0 0
Thailand
State/province [6] 0 0
Khon Kaen

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
DCR-HBVS will be evaluated for safety and efficacy in healthy volunteers and chronic
hepatitis B patients.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03772249
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Thomas Bowman, MD
Address 0 0
Dicerna Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03772249