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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03762681




Registration number
NCT03762681
Ethics application status
Date submitted
30/11/2018
Date registered
4/12/2018

Titles & IDs
Public title
A Study of RO7239958 to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Volunteers and Participants With Chronic Hepatitis B Virus Infection
Scientific title
A Randomized, Placebo-controlled,Observer-blinded Study, to Evaluate Safety,Tolerability, Pharmacokinetics and Pharmacodynamics of RO7239958 in Healthy Volunteers and Patients With Chronic Hepatitis B Virus Infection
Secondary ID [1] 0 0
2018-003530-32
Secondary ID [2] 0 0
NP40520
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B Virus Infection 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections
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 - RO7239958
Other interventions - Placebo

Experimental: Part 1: Single Ascending Dose, HV - Healthy volunteers will be administered a single dose of RO7239958 or placebo subcutaneously (SC).

Experimental: Part 2a: Multi-dose, CHB - Participants with chronic hepatitis B will be administered different dose levels of RO7239958 or placebo SC. Dosages will be determined from data collected from Part 1.

Experimental: Part 2b: Multi-dose, CHB (Optional) - Additional study arm to open based on data collected from Part 2a. Participants with chronic hepatitis B will be administered different doses and frequencies of RO7239958 or placebo SC.


Treatment: Drugs: RO7239958
Solution for injection, subcutaneous use (SC).

Other interventions: Placebo
Sodium chloride solution for injection, SC
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 Adverse Events (AEs)
Timepoint [1] 0 0
Up to approximately 16 months
Primary outcome [2] 0 0
Number of Participants With Clinically Significant Changes in Vital Signs
Timepoint [2] 0 0
Up to approximately 16 months
Primary outcome [3] 0 0
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings
Timepoint [3] 0 0
Up to approximately 16 months
Primary outcome [4] 0 0
Number of Participants With Clinically Significant Changes in Clinical Laboratory Results
Timepoint [4] 0 0
Up to approximately 16 months
Primary outcome [5] 0 0
Number of Participants With Injection Site Reactions (ISRs)
Timepoint [5] 0 0
Up to approximately 16 months
Secondary outcome [1] 0 0
Maximum Plasma Concentration (Cmax) of RO7239958
Timepoint [1] 0 0
Part 1: pre-dose on Day 1 and post-dose at 15 minutes (min), 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 30, 36, 48, 72, 96, 120, 168 hours. Part 2a: pre-dose on Days 1 and 29 and post-dose at 30 min, 1, 2, 4, 6, 8, 24 hours.
Secondary outcome [2] 0 0
Time to Cmax (Tmax) of RO7239958
Timepoint [2] 0 0
Part 1: pre-dose on Day 1 and post-dose at 15 minutes (min), 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 30, 36, 48, 72, 96, 120, 168 hours. Part 2a: pre-dose on Days 1 and 29 and post-dose at 30 min, 1, 2, 4, 6, 8, 24 hours.
Secondary outcome [3] 0 0
Area Under the Curve From Time 0 to the Last Measurable Concentration (AUClast) of RO7239958
Timepoint [3] 0 0
Part 1: pre-dose on Day 1 and post-dose at 15 minutes (min), 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 30, 36, 48, 72, 96, 120, 168 hours. Part 2a: pre-dose on Days 1 and 29 and post-dose at 30 min, 1, 2, 4, 6, 8, 24 hours.
Secondary outcome [4] 0 0
Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of RO7239958
Timepoint [4] 0 0
Part 1: pre-dose on Day 1 and post-dose at 15 minutes (min), 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 30, 36, 48, 72, 96, 120, 168 hours. Part 2a: pre-dose on Days 1 and 29 and post-dose at 30 min, 1, 2, 4, 6, 8, 24 hours.
Secondary outcome [5] 0 0
Half-life (t1/2) of RO7239958
Timepoint [5] 0 0
Part 1: pre-dose on Day 1 and post-dose at 15 minutes (min), 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 30, 36, 48, 72, 96, 120, 168 hours. Part 2a: pre-dose on Days 1 and 29 and post-dose at 30 min, 1, 2, 4, 6, 8, 24 hours.
Secondary outcome [6] 0 0
Cumulative Amount of Drug Excreted in Urine (Ae)
Timepoint [6] 0 0
Part 1: 0-4 h, 0-8 h, 0-12 h and 0-24 h on Day 1; Part 2a: 0-4 h and 0-8 h on Days 1 and 29
Secondary outcome [7] 0 0
Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels
Timepoint [7] 0 0
Part 2a: Days 1 (pre-dose), 8, 15, 22, 29 (pre-dose); at discontinuation (DC) and at follow-up visits 14, 28, 56, and 84 days after the last dose of study drug (up to 16 weeks)
Secondary outcome [8] 0 0
Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels
Timepoint [8] 0 0
Part 2a: Days 1 (pre-dose), 8, 15, 22, 29 (pre-dose); at discontinuation (DC) and at follow-up visits 14, 28, 56, and 84 days after the last dose of study drug (up to 16 weeks)
Secondary outcome [9] 0 0
Part 2a: Number of Participants With HBsAg Loss
Timepoint [9] 0 0
Part 2a: Days 1 (pre-dose), 8, 15, 22, 29 (pre-dose); at discontinuation (DC) and at follow-up visits 14, 28, 56, and 84 days after the last dose of study drug (up to 16 weeks)
Secondary outcome [10] 0 0
Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants
Timepoint [10] 0 0
Part 2a: Days 1 (pre-dose), 8, 15, 22, 29 (pre-dose); at discontinuation (DC) and at follow-up visits 14, 28, 56, and 84 days after the last dose of study drug (up to 16 weeks)
Secondary outcome [11] 0 0
Part 2a: Number of Participants With Hepatitis B e Antibody (Anti-HBe) Seroconversion in HBeAg-positive Participants
Timepoint [11] 0 0
Part 2a: Days 1 (pre-dose), 8, 15, 22, 29 (pre-dose); at discontinuation (DC) and at follow-up visits 14, 28, 56, and 84 days after the last dose of study drug (up to 16 weeks)
Secondary outcome [12] 0 0
Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification
Timepoint [12] 0 0
Part 2a: Day 1 (pre-dose), 15, 29 (pre-dose); at discontinuation (DC), rebound and at follow-up visits 14, 28, 56, and 84 days after the last dose of study drug (up to 16 weeks)

Eligibility
Key inclusion criteria
All Parts

-Female participants should be of non-childbearing potential and male participants who are with pregnant partners or partners of childbearing potential must agree to remain abstinent or use contraceptive measures

Part 1 (SAD HV only)

* Healthy, as judged by the Investigator
* Non-smoker (nor tobacco containing products) for at least 90 days prior to dosing on Day 1, and agrees to remain non-smoker during the study

Part 2 (CHB only)

* Positive serum HBsAg status for > 6 months prior to screening
* Serum HBsAg level = 250 IU/mL at screening
* On stable entecavir or tenofovir (alone or in combination) treatment and having received the same drug in the 3 months prior to randomisation
* HBV DNA below the lower limit of quantification (LLQ) for = 6 months prior to screening by local testing, and confirmed at screening
* Screening laboratory values (including hematology, chemistry, urinalysis) within normal ranges
* No past or current diagnosis of cirrhosis
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
All Parts

* History or presence of significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological disorders, or diagnosed central or peripheral neurological disease, capable of altering the absorption, metabolism, or elimination of drugs, or constituting a risk when taking the study treatment, or of interfering with the interpretation of the data
* History of lymphoma, leukemia, or malignancy within the past five years
* Positive for human immunodeficiency virus (HIV) infection
* Participant under judicial supervision, guardianship or curatorship

Part 1 (SAD HV only)

* Screening ECG showing clinically relevant abnormalities
* Abnormal blood pressure
* History or presence of liver disease, or known hepatic or biliary abnormalities
* Alanine aminotransferase (ALT) =1.5 × upper limit of normal (ULN)
* Any clinically significant out of range findings in other laboratory test results or any other clinically significant (as judged by the Investigator) abnormalities in the physical examination at screening and on Day -1
* Positive for hepatitis B surface antigen (HBsAg), or hepatitis B core total antibody [anti-HBc]), or hepatitis C virus (HCV) antibody test result

Part 2 (CHB only)

* History or presence of bridging fibrosis or cirrhosis or decompensated liver disease
* History or presence of a medical condition associated with liver disease other than HBV infection. Other known hepatic or biliary abnormalities
* History of or suspicion of hepatocellular carcinoma or alpha fetoprotein (AFP) =13 ng/mL
* History of having received (in the last six months) or currently receiving any systemic antineoplastic (including radiation) or immune-modulatory treatment (including systemic corticosteroids)
* History of organ transplantation
* Estimated glomerular filtration rate (eGFR) <70 mL/min/1.73m^2
* Confirmed QT interval corrected using Fridericia's formula (QTcF) >450 ms
* Expected to need any other systemic antiviral therapy at any time during participation in the study
* Positive hepatitis C antibody test

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 assessing the outcomes
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
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/12/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/04/2020
Sample size
Target
Accrual to date
Final
55
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Bulgaria
State/province [1] 0 0
Sofia
Country [2] 0 0
Hong Kong
State/province [2] 0 0
Hong Kong
Country [3] 0 0
Korea, Republic of
State/province [3] 0 0
Busan
Country [4] 0 0
Korea, Republic of
State/province [4] 0 0
Seoul
Country [5] 0 0
New Zealand
State/province [5] 0 0
Auckland
Country [6] 0 0
Poland
State/province [6] 0 0
Myslowice
Country [7] 0 0
Taiwan
State/province [7] 0 0
Kaohsiung
Country [8] 0 0
Taiwan
State/province [8] 0 0
Tainan
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Edinburgh
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Liverpool
Country [11] 0 0
United Kingdom
State/province [11] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03762681