Clinical trial NCT03365947: Study of ARO-HBV in Normal Adult Volunteers and Patients With Hepatitis B Virus (HBV)
Official title: A Phase 1/2a Single Dose-Escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetic Effects of ARO-HBV in Normal Adult Volunteers and Multiple Escalating Doses Evaluating Safety, Tolerability and Pharmacodynamic Effects in HBV Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hepatitis B
Lead sponsor: Arrowhead Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-12-08
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple-ascending doses of ARO-HBV in healthy adult volunteers and participants with hepatitis B virus (HBV).


Eligibility criteria: Inclusion Criteria for Parts A \& B:

* Women of childbearing potential must have a negative pregnancy test, cannot be breast feeding, and must be willing to use contraception.
* Willing to provide written informed consent and comply with study requirements

Additional Inclusion Criteria for Part B:

* Diagnosis of chronic HBV infection
* Hepatitis B surface antigen (HbsAg) at screening \> or = 50 IU/mL
* Liver Elastography score \< or = 10.5

Exclusion Criteria:

* Clinically significant health concerns (with the exception of HBV for Patients in Part B)
* Abnormal for any clinical safety laboratory result considered clinically significant
* Regular use of alcohol within 1 month prior to screening
* Recent use of illicit drugs
* Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study

NOTE: additional inclusion/exclusion criteria may apply, per protocol

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Possibly or Probably Related to Treatment
timeFrame: NHV participants: up to Day 29 (± 2 days); CHB participants: Day 113 (± 2 days)
Secondary outcomes:
measure: Part A, Pharmacokinetics (PK) of ARO-HBV Analytes: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
measure: Part A, PK of ARO-HBV Analytes : Time to Maximum Plasma Concentration (Tmax)
timeFrame: Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
measure: Part A, PK of ARO-HBV Analytes: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24)
timeFrame: Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 hours post-dose
measure: Part A, PK of ARO-HBV Analytes: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf)
timeFrame: Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
measure: Part A, PK of ARO-HBV Analytes: Area Under the Plasma Concentration Versus Time Curve From Zero to the Time of the Last Quantifiable Concentration (AUC0-t)
timeFrame: Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
measure: Part A, PK of ARO-HBV Analytes: Terminal Elimination Half-Life (t½)
timeFrame: Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
measure: Part A, PK of ARO-HBV Analytes: Dose-Normalized AUC0-24
timeFrame: Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 hours post-dose
measure: Part A, PK of ARO-HBV Analytes: Dose-Normalized AUC0-t
timeFrame: Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
measure: Part A, PK of ARO-HBV Analytes: Dose-Normalized Cmax
timeFrame: Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
measure: Change From Baseline in HBV Surface Antigen (HBsAg) From Day 1 Pre-Dose Baseline to Post-Dose Nadir in Participants Chronically Infected With HBV
timeFrame: Part B (multiple-ascending dose [MAD] phase) only: up to 113 days
Other outcomes:
Locations:
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Melbourne
country: Australia
facility: St. Vincent's Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Linear Research
state: Western Australia
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Grafton
country: New Zealand
facility: Auckland Clinical Studies Limited
state: Auckland
city: Papatoetoe
country: New Zealand
facility: Middlemore Clinical Trials
state: Auckland
Study officials:
References:
citation: Yuen MF, Locarnini S, Lim TH, Strasser SI, Sievert W, Cheng W, Thompson AJ, Given BD, Schluep T, Hamilton J, Biermer M, Kalmeijer R, Beumont M, Lenz O, De Ridder F, Cloherty G, Ka-Ho Wong D, Schwabe C, Jackson K, Lai CL, Gish RG, Gane E. Combination treatments including the small-interfering RNA JNJ-3989 induce rapid and sometimes prolonged viral responses in patients with CHB. J Hepatol. 2022 Nov;77(5):1287-1298. doi: 10.1016/j.jhep.2022.07.010. Epub 2022 Jul 20.
citation: Gane E, Yuen MF, Kakuda TN, Ogawa T, Takahashi Y, Goeyvaerts N, Lonjon-Domanec I, Vaughan T, Schluep T, Hamilton J, Njumbe Ediage E, Hillewaert V, Snoeys J, Lenz O, Talloen W, Biermer M. JNJ-73763989 pharmacokinetics and safety: Liver-targeted siRNAs against hepatitis B virus, in Japanese and non-Japanese healthy adults, and combined with JNJ-56136379 and a nucleos(t)ide analogue in patients with chronic hepatitis B. Antivir Ther. 2022 Jun;27(3):13596535221093856. doi: 10.1177/13596535221093856.