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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03365947




Registration number
NCT03365947
Ethics application status
Date submitted
4/12/2017
Date registered
8/12/2017
Date last updated
4/06/2024

Titles & IDs
Public title
Study of ARO-HBV in Normal Adult Volunteers and Patients With Hepatitis B Virus (HBV)
Scientific 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
Secondary ID [1] 0 0
AROHBV1001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B 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 - ARO-HBV
Other interventions - Sterile Normal Saline (0.9% NaCl)
Treatment: Drugs - JNJ-56136379

Experimental: ARO-HBV 35 mg - Single dose of ARO-HBV 35 mg subcutaneous (sc) injection in normal healthy volunteers

Experimental: ARO-HBV 100 mg - Single dose of ARO-HBV 100 mg sc injection in normal healthy volunteers

Experimental: ARO-HBV 200 mg - Single dose of ARO-HBV 200 mg sc injection in normal healthy volunteers

Experimental: ARO-HBV 300 mg - Single dose of ARO-HBV 300 mg sc injection in normal healthy volunteers

Experimental: ARO-HBV 400 mg - Single dose of ARO-HBV 400 mg sc injection in normal healthy volunteers

Placebo comparator: Placebo - Sterile normal saline (0.9% NaCl) sc injection in normal healthy volunteers

Experimental: ARO-HBV 25 mg, Q28D - ARO-HBV 25 mg sc injection every 28 days (Q28D) in participants with chronic hepatitis B

Experimental: ARO-HBV 50 mg Q28D - ARO-HBV 50 mg sc injection Q28D in participants with chronic hepatitis B

Experimental: ARO-HBV 100 mg Q28D - ARO-HBV 100 mg sc injection Q28D in participants with chronic hepatitis B

Experimental: ARO-HBV 200 mg Q28D - ARO-HBV 200 mg sc injection Q28D in participants with chronic hepatitis B

Experimental: ARO-HBV 300 mg Q28D - ARO-HBV 300 mg sc injection Q28D in participants with chronic hepatitis B

Experimental: ARO-HBV 400 mg Q28D - ARO-HBV 400 mg sc injection Q28D in participants with chronic hepatitis B

Experimental: ARO-HBV 100 mg Q14D - ARO-HBV 100 mg sc injection every 14 days (Q14D) in participants with chronic hepatitis B

Experimental: ARO-HBV 100 mg Q7D - ARO-HBV 100 mg sc injection every 7 days (Q7D) in participants with chronic hepatitis B

Experimental: ARO-HBV 300 mg, Q28D, HBeAg+/ Trt Naïve - ARO-HBV 300 mg sc injection Q28D in hepatitis B e antigen positive/treatment naïve (HBeAg+/Trt Naïve) participants with chronic hepatitis B

Experimental: ARO-HBV 300 mg, Q28D, HBeAg+/ NUC - ARO-HBV 300 mg sc injection Q28D in HBeAg+/nucleotide or nucleoside analog treated (HBeAg+/NUC) participants with chronic hepatitis B

Experimental: ARO-HBV 200 mg, Q7D - ARO-HBV 200 mg sc injection Q7D in participants with chronic hepatitis B

Experimental: ARO-HBV 300 mg, Q7D - ARO-HBV 300 mg sc injection Q7D in participants with chronic hepatitis B

Experimental: ARO-HBV 200 mg Q28D + JNJ-56136379 250 mg - ARO-HBV 200 mg sc injection Q28D plus JNJ-56136379 250 mg in participants with chronic hepatitis B


Treatment: Drugs: ARO-HBV
sc injection

Other interventions: Sterile Normal Saline (0.9% NaCl)
sc injection

Treatment: Drugs: JNJ-56136379
oral tablets
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Possibly or Probably Related to Treatment
Timepoint [1] 0 0
NHV participants: up to Day 29 (± 2 days); CHB participants: Day 113 (± 2 days)
Secondary outcome [1] 0 0
Part A, Pharmacokinetics (PK) of ARO-HBV Analytes: Maximum Observed Plasma Concentration (Cmax)
Timepoint [1] 0 0
Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
Secondary outcome [2] 0 0
Part A, PK of ARO-HBV Analytes : Time to Maximum Plasma Concentration (Tmax)
Timepoint [2] 0 0
Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
Secondary outcome [3] 0 0
Part A, PK of ARO-HBV Analytes: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24)
Timepoint [3] 0 0
Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 hours post-dose
Secondary outcome [4] 0 0
Part A, PK of ARO-HBV Analytes: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf)
Timepoint [4] 0 0
Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
Secondary outcome [5] 0 0
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)
Timepoint [5] 0 0
Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
Secondary outcome [6] 0 0
Part A, PK of ARO-HBV Analytes: Terminal Elimination Half-Life (t½)
Timepoint [6] 0 0
Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
Secondary outcome [7] 0 0
Part A, PK of ARO-HBV Analytes: Dose-Normalized AUC0-24
Timepoint [7] 0 0
Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 hours post-dose
Secondary outcome [8] 0 0
Part A, PK of ARO-HBV Analytes: Dose-Normalized AUC0-t
Timepoint [8] 0 0
Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
Secondary outcome [9] 0 0
Part A, PK of ARO-HBV Analytes: Dose-Normalized Cmax
Timepoint [9] 0 0
Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
Secondary outcome [10] 0 0
Change From Baseline in HBV Surface Antigen (HBsAg) From Day 1 Pre-Dose Baseline to Post-Dose Nadir in Participants Chronically Infected With HBV
Timepoint [10] 0 0
Part B (multiple-ascending dose [MAD] phase) only: up to 113 days

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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

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 analysing the results/data
Intervention assignment
Parallel
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
27/03/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/04/2020
Sample size
Target
Accrual to date
Final
114
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [3] 0 0
St. Vincent's Hospital - Melbourne
Recruitment hospital [4] 0 0
Linear Research - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3065 - Melbourne
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Hong Kong
State/province [1] 0 0
Hong Kong
Country [2] 0 0
New Zealand
State/province [2] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Arrowhead Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT03365947
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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/study/NCT03365947