The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03762681
Ethics application status
Date submitted
30/11/2018
Date registered
4/12/2018
Date last updated
5/06/2019

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
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 - Participants will be administered RO7239958 or placebo subcutaneously (SC).

Experimental: Part 2a: Multi-dose, CHB - Participants 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 will be administered different doses and frequencies of RO7239958 or placebo SC.


Treatment: Drugs: RO7239958
Subcutaneous (SC) dose administration as per the schedule specified in the respective arm.

Other interventions: Placebo
Subcutaneous (SC) dose administration as per the schedule specified in the respective arm.

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
Incidence of Adverse Events (AEs)
Timepoint [1] 0 0
Baseline up to 85 days
Secondary outcome [1] 0 0
Part 1: Maximum plasma concentration (Cmax) of RO7239958
Timepoint [1] 0 0
Days 1-6 and Day 8 of Period 1 (Period 1 = 8 days), Day 22 and at early termination
Secondary outcome [2] 0 0
Part 1: Time to Cmax (Tmax) of RO7239958
Timepoint [2] 0 0
Days 1-6 and Day 8 of Period 1 (Period 1 = 8 days), Day 22 and at early termination
Secondary outcome [3] 0 0
Part 1: Area under the curve (AUC) for various time intervals post-dose
Timepoint [3] 0 0
Days 1-6 and Day 8 of Period 1 (Period 1 = 8 days), Day 22 and at early termination
Secondary outcome [4] 0 0
Parts 2a,2b: Maximum plasma concentration (Cmax) of RO7239958
Timepoint [4] 0 0
Days 1-2, Day 8, Day 15, Day 22, Days 29-30; at discontinuation (DC) and at follow-up visits occurring 14, 28, 56, and 84 days after the last dose of study drug
Secondary outcome [5] 0 0
Parts 2a,2b: Time to Cmax (Tmax) of RO7239958
Timepoint [5] 0 0
Days 1-2, Day 8, Day 15, Day 22, Days 29-30; at DC and at follow-up visits occurring 14, 28, 56, and 84 days after the last dose of study drug
Secondary outcome [6] 0 0
Parts 2a,2b: Area under the curve (AUC) for various time intervals post-dose
Timepoint [6] 0 0
Days 1-2, Day 8, Day 15, Day 22, Days 29-30; at DC and at follow-up visits occurring 14, 28, 56, and 84 days after the last dose of study drug
Secondary outcome [7] 0 0
Parts 2a,2b: Incidence of HBeAg loss
Timepoint [7] 0 0
At screening (Day 29 to Day 2), Day 1, Day 8, Day 15, Day 22, Day 29, at DC, at safety and follow-up visits occurring 14, 28, 68 and 84 days after the last dose of the study drug; (Part 2b) Day 43, Day 57 and Day 71
Secondary outcome [8] 0 0
Parts 2a,2b: Incidence of hepatitis B e antibody (anti- HBe) seroconversion
Timepoint [8] 0 0
At screening (Day 29 to Day 2), Day 1, Day 8, Day 15, Day 22, Day 29, at DC, at safety and follow-up visits occurring 14, 28, 68 and 84 days after the last dose of the study drug; (Part 2b) Day 43, Day 57 and Day 71
Secondary outcome [9] 0 0
Parts 2a,2b: Change from baseline in HBsAg levels
Timepoint [9] 0 0
At screening (Day 29 to Day 2), Day 1, Day 8, Day 15, Day 22, Day 29, at DC, at safety and follow-up visits occurring 14, 28, 68 and 84 days after the last dose of the study drug; (Part 2b) Day 43, Day 57 and Day 71

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. Healthy status will be defined as the absence
of evidence of any active or chronic disease following a detailed medical and surgical
history, concomitant drug use (including hormonal supplements), a complete physical
examination including vital signs, 12-lead ECG, haematology, blood chemistry,
serology, and urinalysis

- 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, or judged to be not clinically significant by the Investigator and
Medical Monitor

- No past or current diagnosis of cirrhosis. Transient elastography at screening showing
a kPa value consistent with a degree of liver fibrosis not higher than F3. By
FibroScan, a cut-off of < 8.5 kPa in the fasted status (last meal =3 hours prior) is
recommended
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Part 1 (SAD HV only)

- History or presence of significant cardiovascular, respiratory, hepatic, renal,
gastrointestinal, endocrine, haematological disorders, or diagnosed central or
peripheral neurological disease, capable of significantly 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

- Screening ECG showing clinically relevant abnormalities

- Abnormal blood pressure at the time of screening

- History of lymphoma, leukaemia, or malignancy within the past five years

- History or presence of liver disease, or known hepatic or biliary abnormalities

- ALT =1.5 × ULN at screening and at Day -1

- 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

- Known positive for hepatitis B surface antigen (HBsAg), or hepatitis B core total
antibody [anti-HBc]), or hepatitis C virus (HCV) antibody test result at screening

- Known positive for human immunodeficiency virus (HIV) infection and/or positive for
HIV infection at screening

- Healthy participants under judicial supervision, guardianship or curatorship

Part 2 (CHB only)

- History or presence of significant cardiovascular (including poorly controlled blood
hypertension), respiratory, hepatic, renal, gastrointestinal, endocrine,
haematological 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 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 at screening

- History of lymphoma, leukaemia, or malignancy within the past five years

- 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) &lt; 70 mL/min/1.73m2

- Confirmed QT interval corrected using Fridericia's formula (QTcF) &gt;450 ms

- Expected to need any other systemic antiviral therapy at any time during participation
in the study

- Positive hepatitis C antibody at screening

- Known positive for human immunodeficiency virus (HIV) infection and/or positive for
HIV infection at screening

- Patients under judicial supervision, guardianship or curatorship

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
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
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study is designed to assess the safety, tolerability, pharmacokinetics (PK) and
pharmacodynamics (PD) of single and multiple ascending doses in healthy participants and
participants diagnosed with chronic hepatitis B (CHB).
Trial website
https://clinicaltrials.gov/show/NCT03762681
Trial related presentations / publications
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
Reference Study ID Number: NP40520 www.roche.com/about_roche/roche_worldwide.htm
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
global-roche-genentech-trials@gene.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03762681