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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03772249
Ethics application status
Date submitted
3/12/2018
Date registered
11/12/2018
Date last updated
7/03/2019

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)


Treatment: Drugs: DCR-HBVS
DCR-HBVS is a synthetic ribonucleic acid interference (RNAi) drug that consists of double-stranded oligonucleotides conjugated to an N-acetyl-D-galactosamine (GalNAc) ligand. DCR-HBVS, sterile solution of the siRNA (DCR-S219) at a concentration of 185 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 - Number of participants with abnormalities in vital signs, electrocardiogram (ECG), and clinically significant laboratory findings
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 - Number of participants with abnormalities in vital signs, electrocardiogram (ECG), and clinically significant laboratory findings
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 - Measure the amount of DCR-HBVS excreted in urine
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 - Measure the amount of DCR-HBVS renal clearance (CLR).
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. - Measure the amount of DCR-HBVS excreted in urine
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. - Measure DCR-HBVS renal clearance (CLR).
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
Gender
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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Dicerna Pharmaceuticals, Inc.
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/show/NCT03772249
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ralf Rosskamp, 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
Sr Director, Clinical Development
Address 0 0
Country 0 0
Phone 0 0
617-612-6260
Fax 0 0
Email 0 0
mcioffi@dicerna.com
Contact person for scientific queries

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