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

Roche

Status and phase: Terminated; Phase 1

Conditions: Hepatitis B Virus Infection

Treatments: Other: Placebo; Drug: RO7239958

Study type: Interventional

Funder types: Industry

Identifiers

NCT03762681

2018-003530-32 (EudraCT Number)

NP40520

Details and patient eligibility

About

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).

Enrollment: 55 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

---

55 participants in 3 patient groups

Part 1: Single Ascending Dose, HV

Experimental group

Description:

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

Treatment:

Other: Placebo

Drug: RO7239958

Part 2a: Multi-dose, CHB

Experimental group

Description:

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.

Treatment:

Other: Placebo

Drug: RO7239958

Part 2b: Multi-dose, CHB (Optional)

Experimental group

Description:

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:

Other: Placebo

Drug: RO7239958