A Study of RO7239958 to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Volunteers and Participants With Chronic Hepatitis B Virus Infection

NCT03762681 | Terminated Phase 1 Results

• 2 other identifiers: NP405202018-003530-32
• Study Type: interventional
• Target: 55
• Locations: 7 countries
• Sites: 14

Brief 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).

Conditions

Hepatitis B Virus Infection

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  Up to approximately 16 months

• Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings

  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.

  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.

  Up to approximately 16 months

Secondary Outcomes (12)

• Maximum Plasma Concentration (Cmax) of RO7239958

  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

  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

  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

  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

  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.

Study Arms (3)

Part 1: Single Ascending Dose, HV

EXPERIMENTAL

Healthy volunteers will be administered a single dose of RO7239958 or placebo subcutaneously (SC).

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.

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.

Drug: RO7239958; Other: Placebo

Interventions

RO7239958 DRUG

Solution for injection, subcutaneous use (SC).

Part 1: Single Ascending Dose, HV; Part 2a: Multi-dose, CHB; Part 2b: Multi-dose, CHB (Optional)

Placebo OTHER

Sodium chloride solution for injection, SC

Part 1: Single Ascending Dose, HV; Part 2a: Multi-dose, CHB; Part 2b: Multi-dose, CHB (Optional)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (14)

Acibadem City Clinic Tokuda Hospital Ead

Sofia, 1407, Bulgaria

Location

COMAC Medical; Clinical Research Unit for Phase I

Sofia, 1612, Bulgaria

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Auckland Clinical Studies Limited

Auckland, 1010, New Zealand

Location

ID Clinic

Mysłowice, 41-400, Poland

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Asan Medical Center.

Seoul, 138-736, South Korea

Location

Kaohsiung Medical University

Kaohsiung City, 807, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 70457, Taiwan

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, L7 8XP, United Kingdom

Location

King College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

Chelsea & Westminster Hospital

London, SW10 9NH, United Kingdom

Location

St George's Hospital

London, SW17 0QT, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 41186228 DERIVED

MeSH Terms

Conditions

Hepatitis B

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2018
• First Posted: December 4, 2018
• Study Start: December 14, 2018
• Primary Completion: April 6, 2020
• Study Completion: April 6, 2020
• Last Updated: May 11, 2021
• Results First Posted: April 9, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share

Locations

KR (2); NZ (1); BU (2); GB (5); PL (1); HK (1); TW (2)