Hepatitis B Virus InfectionPhase 1NCT03762681
A Study of RO7239958 to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Volunteers and Participants With Chronic Hepatitis B Virus Infection
A Phase 1 study testing RO7239958 in people with Hepatitis B Virus Infection, run by Hoffmann-La Roche at 14 sites in 7 countries.
Trial summary
This study is designed to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple ascending doses in healthy volunteers (HV) and participants diagnosed with chronic hepatitis B (CHB). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis B Virus Infection
- What is being tested?
- RO7239958
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 55 participants
- Where
- 14 sitesin 7 countries
- Study dates
- 14 Dec 2018to 6 Apr 2020
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
14 sites in 7 countries.
14 sites in 7 countries
United Kingdom5 sites
Western General Hospital
Edinburgh, EH4 2XU
Royal Liverpool University Hospital
Liverpool, L7 8XP
King College Hospital NHS Foundation Trust
London, SE5 9RS
Chelsea & Westminster Hospital
London, SW10 9NH
St George's Hospital
London, SW17 0QT
Bulgaria2 sites
Acibadem City Clinic Tokuda Hospital Ead
Sofia, 1407
COMAC Medical; Clinical Research Unit for Phase I
Sofia, 1612
South Korea2 sites
Pusan National University Hospital
Busan, 49241
Asan Medical Center.
Seoul, 138-736
Taiwan2 sites
Kaohsiung Medical University
Kaohsiung City, 807
National Cheng Kung University Hospital
Tainan, 70457
About this study
Official 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
This study is designed to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple ascending doses in healthy volunteers (HV) and participants diagnosed with chronic hepatitis B (CHB).
- Conditions
- Hepatitis B Virus Infection
- Being tested
- RO7239958, Placebo
- Medical subject headings
- Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RO7239958Drug
Solution for injection, subcutaneous use (SC).
PlaceboOther
Sodium chloride solution for injection, SC
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Single Ascending Dose, HV | Experimental | Healthy volunteers will be administered a single dose of RO7239958 or placebo subcutaneously (SC). Receives: Drug: RO7239958; Other: Placebo |
| Part 2a: Multi-dose, CHB | Experimental | 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. Receives: Drug: RO7239958; Other: Placebo |
| Part 2b: Multi-dose, CHB (Optional) | Experimental | 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. Receives: Drug: RO7239958; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs)
An adverse event (AE) was defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product (including investigational drug) during the course of a clinical investigation. An AE could therefore be any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease that was temporally associated with the use of the investigational product, regardless of whether it was considered to be related to the investigational product or not.
Measured: Up to approximately 16 months
Number of Participants With Clinically Significant Changes in Vital Signs
Number of participants with clinically significant abnormalities in vital signs such as systolic and diastolic blood pressure, heart rate, body temperature were evaluated.
Measured: Up to approximately 16 months
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings
Measured: Up to approximately 16 months
Number of Participants With Clinically Significant Changes in Clinical Laboratory Results
Number of participants with clinically significant abnormalities in clinical laboratory parameters such as serum chemistry, hematology, coagulation, viral serology, urinalysis were evaluated.
Measured: Up to approximately 16 months
Number of Participants With Injection Site Reactions (ISRs)
Injection site reactions (ISRs) referred to any localized sign or symptom, including pain, erythema, swelling and pruritus and were graded as follows: Grade 1: mild, Grade 2: moderate; Grade 3: severe. Adverse events related to ISRs were reported.
Measured: Up to approximately 16 months
Secondary outcomes (12)
Maximum Plasma Concentration (Cmax) of RO7239958
Measured: 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.
Time to Cmax (Tmax) of RO7239958
Measured: 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.
Area Under the Curve From Time 0 to the Last Measurable Concentration (AUClast) of RO7239958
Measured: 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.
Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of RO7239958
Measured: 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.
Half-life (t1/2) of RO7239958
Measured: 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.
Cumulative Amount of Drug Excreted in Urine (Ae)
The cumulative amount of drug excreted in urine (Ae) over a 24 hour period or over defined time periods linked to the pools of urine collected was analyzed.
Measured: 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
Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels
Measured: 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)
Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels
Measured: 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)
Part 2a: Number of Participants With HBsAg Loss
HBsAg loss was defined as a measurement below the lower limit of sensitivity.
Measured: 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)
Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants
HBeAg loss was defined as a measurement below lower limit of sensitivity. Positive HBeAg is a marker of an actively replicating HBV virus infection.
Measured: 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)
Part 2a: Number of Participants With Hepatitis B e Antibody (Anti-HBe) Seroconversion in HBeAg-positive Participants
Anti-HbBe was defined as an antibody to HBeAg. Positive HBeAg is a marker of an actively replicating HBV virus infection.
Measured: 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)
Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification
Participants with HBV DNA below the assay lower limit of quantification i.e. LLOQ <20 IU/ml at each time-point were analyzed.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2018
- Study start14 Dec 2018
- Primary completion6 Apr 2020
- Study completion6 Apr 2020
Why it stopped: The study was terminated due to program discontinuation.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis B Virus InfectionStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03762681
- Sponsor's protocol ID
- NP40520
- Other IDs
- 2018-003530-32, 2018
- Status last verified
- Apr 2021
- First submitted
- 30 Nov 2018
- Last updated
- 11 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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).
Publications
Geretti AM, Sostelly A, Buatois S, Lu S, Lemenuel A, Attley G, Bopst M, Alvarez-Sanchez R, Mueller H, Gane E. Safety, pharmacokinetics, and pharmacodynamics of the antisense oligonucleotide RO7239958 in healthy volunteers and adults with chronic hepatitis B infection. Antimicrob Agents Chemother. 2025 Dec 10;69(12):e0067925. doi: 10.1128/aac.00679-25. Epub 2025 Nov 4.
PubMed 41186228