Phase 1
Completed N=160
A Study in Healthy Volunteers and in Participants With Chronic Hepatitis B to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of RO7020531
Hepatitis B, Chronic
Source: ClinicalTrials.gov NCT02956850 ↗
Enrolled (actual)
160
Serious AEs
0.6%
Results posted
Feb 2024
Primary outcomePrimary: Part 1: Percentage of SAD Participants With Adverse Events (AEs) — 31.3; 25.0; 50.0; 25.0 percentage of participants
Summary
This sponsor-open, investigator- and participant-blinded, multi-center study will assess the safety, tolerability, pharmacokinetics and pharmacodynamics of RO7020531 in healthy participants and in participants with chronic hepatitis B. Part I will be conducted in two portions: Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) which will include only healthy volunteers. Part II will commence after completion of the MAD portion of Part I and will include only Chronic Hepatitis B (CHB) participants.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Percentage of SAD Participants With Adverse Events (AEs) |
31.3; 25.0; 50.0; 25.0; 25.0; 25.0 | — |
| PRIMARY Part 1: Percentage of MAD Participants With AEs |
83.3; 75.0; 87.5; 87.5 | — |
| PRIMARY Part 2: Percentage of Chronic Hepatitis B Participants With AEs |
50.0; 68.8; 75.0; 60.0; 80.0 | — |
| PRIMARY Part 1: Percentage of SAD Participants With Laboratory Abnormalities Based on Hematology, Clinical Chemistry, Coagulation and Urinalysis Test Results |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 1: Percentage of MAD Participants With Laboratory Abnormalities Based on Hematology, Clinical Chemistry, Coagulation and Urinalysis Test Results |
0; 12.5; 0; 0; 0; 0 | — |
| PRIMARY Part 2: Percentage of Chronic Hepatitis B Participants With Laboratory Abnormalities Based on Hematology, Clinical Chemistry, Coagulation and Urinalysis Test Results |
0; 6.3; 0; 0; 6.7; 0 | — |
| PRIMARY Part 1: Percentage of SAD Participants With Abnormalities in Electrocardiograph (ECG) Parameters |
6.3; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 1: Percentage of MAD Participants With Abnormalities in ECG Parameters |
0; 0; 0; 12.5; 0; 14.3 | — |
| PRIMARY Part 2: Percentage of Chronic Hepatitis B Participants With Abnormalities in ECG Parameters |
0; 0; 0; 0; 6.7; 0 | — |
| PRIMARY Part 1: Percentage of SAD Participants With Abnormalities in Vital Signs |
0; 12.5; 25.0; 0; 0; 0 | — |
| PRIMARY Part 1: Percentage of MAD Participants With Abnormalities in Vital Signs |
0; 0; 0; 12.5; 0; 25.0 | — |
| PRIMARY Part 2: Percentage of Chronic Hepatitis B Participants With Abnormalities in Vital Signs |
33.3; 35.7; 12.5; 60.0; 6.7; 50.0 | — |
| SECONDARY Part 1: Maximum Observed Plasma Concentration (Cmax) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD |
0.00; 0.00; 0.00; 0.00; 0.00; 0.00 | — |
| SECONDARY Part 2: Cmax of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805 |
1.70; 1690; 1500; 1980; 1580; 1430 | — |
| SECONDARY Part 1: Time to Maximum Observed Plasma Concentration (Tmax) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD |
0.00; 0.00; 0.00; 0.00; 0.00; 0.00 | — |
| SECONDARY Part 2: Tmax of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805 |
0.25; 1.00; 1.00; 1.00; 1.040; 1.00 | — |
| SECONDARY Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD |
50.9; 138; 253; 596; 770; 1600 | — |
| SECONDARY Part 2: AUCinf of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805 |
2770; 2430; 3060; 2740; 2500; 2960 | — |
| SECONDARY Part 1: Area Under the Plasma Concentration Versus Time Curve up to the Last Measurable Concentration (AUClast) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD |
0.234; 48.2; 135; 249; 587; 763 | — |
| SECONDARY Part 2: AUClast of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805 |
0.213; 2820; 2400; 3030; 2730; 2470 | — |
| SECONDARY Part 1: Half Life (t1/2) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD |
1.11; 1.56; 1.81; 2.78; 2.82; 3.35 | — |
| SECONDARY Part 2: t1/2 of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805 |
3.09; 2.63; 3.06; 3.09; 2.77; 2.90 | — |
| SECONDARY Part 1: Total Amount of RO7020531, RO7011785, RO7018822 and RO7033805 in Urine: SAD |
0.00; 0.00; 0.00; 0.00; 0.00; 0.00 | — |
| SECONDARY Part 1:Mean Concentration of Interferon Alpha (IFN-alpha): SAD and MAD |
0.0484; 0.0475; 0.0438; 0.0447; 0.0436; 0.0494 | — |
| SECONDARY Part 2: Mean Concentration of IFN-alpha |
0.0533; 0.3801; 0.2831; 0.0574; 0.3161 | — |
| SECONDARY Part 1: Mean Fold Change From Baseline in Cytokine Markers: SAD and MAD |
0.9861; 1.0561; 1.0175; 0.9878; 0.9975; 0.9896 | — |
| SECONDARY Part 2: Mean Fold Change From Baseline in Cytokine Markers |
1.0473; 1.5596; 1.7935; 1.0591; 1.4676; 0.9007 | — |
| SECONDARY Part 1:Mean Fold Change From Baseline in Markers of Transcriptional Responses: SAD and MAD |
0.9709; 1.1708; 1.0525; 0.9386; 1.0799; 1.0190 | — |
| SECONDARY Part 2: Mean Fold Change From Baseline in Markers of Transcriptional Responses |
1.0745; 4.2007; 6.8997; 0.8661; 3.9424; 0.9617 | — |
| SECONDARY Effect of RO7020531 Dosing on ECG Parameters (PR [PQ], QRS, QT, QTcF in Miliseconds [ms]) Using Exposure-response Analysis: SAD and MAD |
— | — |
| SECONDARY Part 2: Plasma Concentrations of Tenofovir, Tenofovir Alafenamide, Entecavir, Adefovir and Telbivudine |
0.467; 0.420; 0.590; 1.974; 1.455; 1.019 | — |
Eligibility Criteria
Inclusion Criteria
Part 1: SAD and MAD in Healthy Volunteers
- Non-smokers, or use of less than ( = 2 × 10*4 IU/mL for HBeAg positive and >= 2 x 10*3 IU/mL for hepatitis B e antigen (HBeAg) negative participants
- For Cohort 1, 2 and 3: Alanine amino transferase (ALT) = /=) Metavir 3, recommended cut-off for Fibroscan 8.5 kilopascals [kPa])
- For Cohort 1, 2 and 3: On treatment with tenofovir, entecavir, adefovir, or telbivudine, either as single agents or in combination, for at least 6 months
- For Cohort 4: Hepatitis B virus (HBV) treatment naïve or not on any anti-HBV treatment for the past 6 months
Exclusion Criteria
Part 1: SAD and MAD in Healthy Volunteers
- History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis, multiple sclerosis, or any other autoimmune disease); clinically significant psychiatric disease, acute infection (e.g., influenza), gastrointestinal (GI) disease (including inflammatory bowel disease, peptic ulcer disease, GI hemorrhage)
- History of having received or currently receiving any systemic anti-neoplastic (including radiation) or immune-modulatory treatment (including systemic oral or inhaled corticosteroids, IFN or pegylated interferon [PEG-IFN]) within the 8 weeks prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study
- Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study
- Positive Hepatitis A virus antibody (HAV Ab IgM), HBsAg, Hepatitis C antibody (HCV Ab), or positive for human immunodeficiency virus (HIV) at screening
- History of clinically significant thyroid disease; also, participants with clinically significant elevated thyroid-stimulating hormone (TSH) concentrations at screening
- Positive results for anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (ASMA) or thyroid peroxidase antibody
Part 2: CHB Participants
- History of liver cirrhosis
- History or other evidence of bleeding from esophageal varices
- Decompensated liver disease (e.g., Child-Pugh Class B or C clinical classification or clinical evidence such as ascites or varices)
- History or other evidence of a medical condition associated with chronic liver disease other than HBV infection (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposure, thalassemia, nonalcoholic steato-hepatitis, etc.). A clinical diagnosis of fatty liver is allowed provided that non alcoholic steatohepatitis (NASH) has been excluded by liver biopsy.
- Documented history or other evidence of metabolic liver disease within one year of randomization
- Positive test for Hepatitis A virus (IgM anti-HAV), Hepatitis C virus (HCV), Hepatitis D virus, Hepatitis E virus (HEV), or human immunodeficiency virus (HIV).
- History of or suspicion of hepatocellular carcinoma or alpha fetoprotein >/=13 nanograms per milliliter (ng/mL) at screening
- History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis, multiple sclerosis, or any other autoimmune disease); clinically significant psychiatric disease; acute infection (e.g., influenza); GI disease (including inflammatory bowel disease, peptic ulcer disease, GI hemorrhage, or history of pancreatitis); clinically significant cardiovascular (including postural hypotension), endocrine, renal, ocular, pulmonary or neurological disease.
- History of having received or currently receiving any systemic anti-neoplastic (including radiation) or immune-modulatory treatment (inc
Data sourced from ClinicalTrials.gov (NCT02956850). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.