Study of Safety and Tolerability of DCR HBVS

Dicerna Pharmaceuticals

Status and phase

Completed

Phase 1

Conditions

Hepatitis B, Chronic

Treatments

Drug: DCR-HBVS

Drug: Placebo for DCR-HBVS

Study type

Interventional

Funder types

Industry

Identifiers

NCT03772249

DCR-HBVS-101

U1111-1220-7021 (Other Identifier)

Details and patient eligibility

About

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

Full 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.

Enrollment

82 patients

Sex

All

Ages

18 to 65 years old

Volunteers

Accepts Healthy Volunteers

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).

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Sequential Assignment

Masking

Triple Blind

82 participants in 22 patient groups, including a placebo group

Cohort A1 DCR-HBVS

Experimental group

Description:

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

Treatment:

Drug: DCR-HBVS

Cohort A1 Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo for DCR-HBVS

Cohort A2 DCR-HBVS

Experimental group

Description:

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

Treatment:

Drug: DCR-HBVS

Cohort A2 Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo for DCR-HBVS

Cohort A3 DCR-HBVS

Experimental group

Description:

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

Treatment:

Drug: DCR-HBVS

Cohort A3 Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo for DCR-HBVS

Cohort A4 DCR-HBVS

Experimental group

Description:

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

Treatment:

Drug: DCR-HBVS

Cohort A4 Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo for DCR-HBVS

Cohort A5 DCR-HBVS

Experimental group

Description:

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

Treatment:

Drug: DCR-HBVS

Cohort A5 Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo for DCR-HBVS

Cohort B DCR-HBVS

Experimental group

Description:

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

Treatment:

Drug: DCR-HBVS

Cohort B Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo for DCR-HBVS

Cohort C1 DCR-HBVS

Experimental group

Description:

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

Treatment:

Drug: DCR-HBVS

Cohort C1 Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo for DCR-HBVS

Cohort C2 DCR-HBVS

Experimental group

Description:

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

Treatment:

Drug: DCR-HBVS

Cohort C2 Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo for DCR-HBVS

Cohort C3 DCR-HBVS

Experimental group

Description:

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

Treatment:

Drug: DCR-HBVS

Cohort C3 Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo for DCR-HBVS

Cohort 4C DCR-HBVS

Experimental group

Description:

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)

Treatment:

Drug: DCR-HBVS

Cohort 5C1 DCR-HBVS

Experimental group

Description:

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

Treatment:

Drug: DCR-HBVS

Cohort 5C2 DCR-HBVS

Experimental group

Description:

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