This is the first-in-human Phase I, double-blind, randomized, placebo-controlled, dose escalating study to evaluate the safety, immunogenicity and preliminary efficacy of the YSHBV-002 in the treatment of CHB in adults ≥18 years old. There will be 3 escalating doses of YS-HBV-002 to be administered intramuscularly: 0.5mL, 1.0mL, and 2.0mL.
This is the first-in-human Phase I, double-blind, randomized, placebo-controlled, dose escalating study to evaluate the safety, immunogenicity and preliminary efficacy of the YSHBV-002 in the treatment of CHB in adults ≥18 years old. There will be 3 escalating doses of YS-HBV-002 to be administered intramuscularly: 0.5mL, 1.0mL, and 2.0mL. Enrollment in the study will sequentially start from the low dose 0.5mL as Group A, then to the mid-dose 1.0mL as Group B and lastly to the high dose of 2.0mL as Group C. Each group will have 16 patients enrolled. The first 4 enrollees in Group A will be sentinel patients and will be allocated at a 1:1 ratio to receive 0.5mL of either YS-HBV-002 or placebo (Table 3). As there is no comparable equivalent to YS-HBV-002 available in the market, the placebo of normal saline solution to be injected intramuscularly will serve as the control in this trial. The next 12 enrollees in Group A will be the main patients and will be allocated at 5:1 to receive 0.5mL of either YS-HBV-002 or placebo. The vaccination regimen will be 1 IM injection every 3 days in the deltoid muscle, alternately for approximately 6 weeks. A total of 14 injections will be administered to each patient.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
16
YS-HBV-002, A recombinant hepatitis B vaccine with PIKA adjuvant
Iloilo Doctors' Hospital
Iloilo City, Philippines
Incidence of AEs within 30 minutes after vaccination.
To assess the safety and tolerability
Time frame: 30 minutes post each vaccination
Incidence of solicited local reactions within 7 days after each vaccination.
To assess the safety and tolerability
Time frame: 7 days post each vaccination
Incidence of solicited systemic reactions from first vaccination to 7 days after the last vaccination (D1 to D46).
To assess the safety and tolerability
Time frame: From Day1 to Day46
Incidence of unsolicited AEs, serious adverse events (SAEs) including suspected unexpected serious adverse reactions (SUSARs), adverse events of special interest (AESIs), and AEs leading to withdrawals throughout the study period
To assess the safety and tolerability
Time frame: From Day1 to Day 90
Proportion of patients showing reduction in HBV DNA using PCR for each dose from baseline to the end of the study and at specified timepoints.
To evaluate the preliminary efficacy, immunogenicity and determine the appropriate dose
Time frame: Day0, Day16, Day34, Day60, Day90
Change in mean log10 of HBV DNA from baseline to end of study and at each specified timepoint.
To evaluate the preliminary efficacy, immunogenicity and determine the appropriate dose
Time frame: Day0, Day16, Day34, Day60, Day90
Change in serum levels of HBeAg, HBcAg, and HBsAg from baseline to end of study at each specified timepoint.
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To evaluate the preliminary efficacy, immunogenicity and determine the appropriate dose
Time frame: Day0, Day16, Day34, Day60, Day90
Change in serum levels of HBeAg, HBcAg, and HBsAg from baseline to end of study and at each specified timepoint.
To evaluate the preliminary efficacy, immunogenicity and determine the appropriate dose
Time frame: Day0, Day16, Day34, Day60, Day90
Proportion of patients with loss (defined as lower limit of quantitation [LLOQ]) or decline in HBsAg, HBcAg, and HBeAg from baseline to the end of the study and at each specified timepoint.
To evaluate the preliminary efficacy, immunogenicity and determine the appropriate dose
Time frame: Day0, Day16, Day34, Day60, Day90
GMTs of antibodies against HBsAg, HBcAg and HBeAg at baseline and at pre-defined post-vaccination timepoints.
To evaluate the preliminary efficacy, immunogenicity and determine the appropriate dose
Time frame: Day0, Day16, Day34, Day60, Day90
Seroconversion rates of antibodies against HBsAg, HBcAg, and HBeAg.
To evaluate the preliminary efficacy, immunogenicity and determine the appropriate dose
Time frame: Day0, Day16, Day34, Day60, Day90