A Multicenter, Randomized, Controlled, Open-label, Phase III Study to Assess Efficacy and Safety of Libevitug Injection in Participants With Chronic Hepatitis Delta Virus Infection (D-clear Study)
Overview
- Phase
- Phase 3
- Status
- Not yet recruiting
- Sponsor
- Huahui Health
- Enrollment
- 160
- Primary Endpoint
- Proportion of participants with HDV RNA below LLOQ with TND or a decrease of ≥ 2 log10 from baseline, and ALT normalization at Week 48 of the treatment period
Overview
Brief Summary
This is an international, multicenter, randomized, controlled, open-label Phase III trial. It will evaluate the efficacy and safety of libevitug in participants with chronic HDV infection. Eligible participants will be randomized 1:1:1 to one of three groups: libevitug 20 mg/kg group , libevitug 10 mg/kg (N=50) group, or a control/delayed treatment group (N=50). The treatment groups will receive intravenous libevitug every 2 weeks for 96 weeks, while the control group will be observed for the first 48 weeks and then receive libevitug 20 mg/kg Q2W for 48 weeks starting from Week 48.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 12 Years to 70 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Willing to sign written informed consent;
- •Male or female, aged 18-70 years; Adolescent participants with chronic HDV infection: Male or female, age ≥12 years and \<18 years at the time of signing the informed consent form (ICF)/assent;
- •Chronic HDV history with at least 6 months; For participants who are also recommended for anti-HBV therapy prior first-line NrtIs treatment (ETV, TDF, TAF) should be at least 12 weeks before the planned start of study treatment, or participant is willing to initiate first-line NrtIs treatment; HBV DNA suppressed;
- •HDV RNA ≥500 IU/mL at screening;
- •ALT \>1×ULN and \<10×ULN at screening;
- •Able to communicate well and comply with protocol.
Exclusion Criteria
- •Concomitant decompensated cirrhosis;
- •Previous or current HCC or suspicion for HCC;
- •Participants with history of alcoholic liver disease, nonalcoholic steatohepatitis, autoimmune liver disease or other hereditary liver diseases, drug-induced liver disease or other clinically significant chronic liver diseases not caused by HDV/HBV;
- •Participants with active hepatitis C infection, or HIV infection;
- •History of other malignancies other than HCC;
- •Clinically significant ECG abnormalities at screening, which is deemed unsuitable for enrollment per investigator's discretion;
- •Alcohol abuse or drug addiction within 1 year;
- •Participants who have participated in clinical trials of any drug or medical device within 1 month before randomization;
- •Pregnant, lactating women, or women of childbearing potential with a positive pregnancy test;
- •Any other clinically significant abnormal lab result, severe acute/chronic medical/psychiatric condition, concomitant serious systemic disease.
Arms & Interventions
Libevitug 20 mg/kg
Participants will receive libevitug at a dose of 20 mg/kg Q2W via intravenous infusion for 96 weeks
Intervention: Libevitug 20 mg/kg (Drug)
Libevitug 10 mg/kg
Participants will receive libevitug at a dose of 10 mg/kg Q2W via intravenous infusion for 96 weeks
Intervention: Libevitug 10 mg/kg (Drug)
Control group/delayed treatment with libevitug 20 mg/kg
Participants will be observed as comparator for 48 weeks, then to receive libevitug 20 mg/kg for 48 weeks
Intervention: Delayed treatment with libevitug (Other)
Outcomes
Primary Outcomes
Proportion of participants with HDV RNA below LLOQ with TND or a decrease of ≥ 2 log10 from baseline, and ALT normalization at Week 48 of the treatment period
Time Frame: Week 48
Proportion of participants with HDV RNA below Lower Limit of Quantification (LLOQ) with target not detected (TND) or a decrease of ≥ 2 log10 from baseline, and ALT normalization at Week 48 of the treatment period
Secondary Outcomes
- Change from baseline in Model for End-Stage Liver Disease (MELD) score at different time points(up to week 96)
- Change from baseline in Child-Pugh score at different time points during the treatment period, extended treatment period and follow-up period. (A higher Child-Pugh score indicates poorer liver function, more severe disease, and a worse prognosis)(up to week 96)
- Percentage of participants with treatment-emergent adverse events (TEAEs)(up to week 120)
- Ctrough,ss(up to week 96)
- Liver related clinical events(up to week 120)
- Change from baseline in MELD score at different time points(up to week 96)
- Change from baseline in Child-Pugh score at different time points(up to week 96)
- Proportion of participants with HDV RNA below LLOQ or a decrease of ≥ 2 log10 from baseline, and ALT normalization(up to week 96)
- Proportion of participants with HDV RNA below LLOQ or a decrease of ≥ 2 log10 from baseline(up to week 96)
- Proportion of participants with plasma HDV RNA achieving HDV RNA < LLOQ(up to week 96)
- Proportion of participants with ALT normalization(up to week 96)
- Change from baseline in liver stiffness measurement (LSM)(up to week 96)
- Change from baseline in plasma HDV RNA levels at different time points(up to week 96)
- AEs, abnormal findings in physical examination, vital signs and lab tests(up to week 120)
- PK analysis(up to week 120)