A Study to Evaluate Efficacy and Safety of Multiple Combination Therapies in Participants with Chronic Hepatitis B

Phase 1

• Conditions: Chronic Hepatitis B (CHB); MedDRA version: 20.1Level: PTClassification code 10008910Term: Chronic hepatitis BSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2019-002086-35-GB
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-12-31
• Last Update Posted: 23 November 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

- Participant must be 18 to 65 years of age
- Body mass index between 18 and 32 kg/m2 inclusive
- Participants with CHB infection (HBsAg [Hepatitis B surface antigen] positive for >= 6 months) who are on established Nucleos[t]ide (NUC) monotherapy for >=12 months, having received the same NUC therapy for >=3 months prior to screening
- Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) below the limit of quantification (LLOQ) or < 20 IU/mL for > 6 months prior to screening and confirmed at screening
- Alanine transaminase (ALT) <=1.5 x upper limit of normal (ULN) for > 6 months prior to screening, and confirmed at screening
- Screening laboratory values within normal range, or judged not clinically significant by the Investigator and Medical Monitor
- Female Participants: Women of non-childbearing potential or women of childbearing potential who agree to remain abstinent or use highly effective contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the final dose of study treatment and willing to undergo a urine pregnancy test every 3 months until the end of the study
- Male Participants: remain abstinent, refrain from donating sperm or use contraceptive measures such as condom with a pregnant female partner or such as condom plus an additional contraceptive method that together result in failure rate of <1% per year with a female partner of childbearing potential during the treatment period and for at least 6 months after the final dose of study treatment
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Pregnant or lactating women
- Co-infection with pathogens such as hepatitis A (HAV), hepatitis C (HCV), hepatitis D (HDV), hepatitis E (HEV), or human immunodeficiency virus (HIV)
- History of cirrhosis or current evidence of significant liver fibrosis or cirrhosis, or decompensated liver disease (e.g., ascites, hepatic encephalopathy). Liver biopsy or transient/ Acoustic radiation force impulse/ magnetic resonance elastography result must be obtained within 6 months prior to randomisation
- History of or suspicion of Hepatocellular carcinoma
- Thyroid disease poorly controlled on prescribed medications or clinically relevant abnormal thyroid function tests at screening, as judged by the Investigator and Medical Monitor
- Clinically significant disease other than CHB that, in the opinion of the Investigator, makes the participant unsuitable for the study
- Pre-existing cardiac disease that in the opinion of the Investigator would increase the risk for the participant to take part in the study
- History of alcohol abuse and/or drug abuse within one year of randomization.
- History of having received (in the last 6 months) or currently receiving any systemic antineoplastic or immunosuppressive or immune modulating treatment for malignant or non-malignant disorders.
- Currently taking, or have received within 3 months of Day 1, systemic corticosteroids at a high-dose (e.g., 40 mg prednisolone per day for) > 7 days, or a low-dose (e.g., 20 mg prednisolone per day) for > 14 days.
- Electrocardiogram with clinically significant abnormalities
- Laboratory parameters at screening
•Hemoglobin < 12 g/dL (females) or < 13 g/dL (males); platelets < lower limit of normal (LLN); international normalized ratio (INR) > 1.1
•Albumin < 3 g/dL; total bilirubin > ULN (exception: Gilbert's disease).
•Positive results for anti-mitochondrial antibodies (AMA > 1:80), antinuclear antibody (ANA > 1:80), anti–smooth muscle antibody (ASMA > 1:40), or anti-thyroperoxidase antibodies (a-TPO > 10)
•White blood cell count < 2500 cells/mm3; neutrophil count < 1500 cells/mm3
•Glomerular filtration rate < 60 mL/min
•Positive test for drugs of abuse and/or positive alcohol test at screening. For positive cannabinoids test, the eligibility is at the
Investigator's discretion.
- Previous treatment with an investigational agent for HBV within 6 months prior to screening
- Unable to comply with any drugs or nutrients listed in prohibited medications and prohibited food sections in the respective treatment arm appendix.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified