Chronic HBV infection
Conditions
Interventions
Placebo group:YKYY013 placebo
Experimental group:YKYY013 injection
Sponsors
Beijing Friendship Hospital ,Capital Medical University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Part One: Healthy Volunteers (1) Age 18–45 years (inclusive), any gender; (2) Body Mass Index (BMI: weight [kg]/height [m]^2) between 18.0 and 28.0 kg/m^2 (inclusive); male participants must weigh =50 kg, female participants must weigh =45 kg; (3) Vital signs, physical examination, laboratory tests, and chest X-ray results show no abnormalities or abnormalities that are clinically insignificant; 12-lead ECG results are normal or, as judged by the investigator, any abnormalities are clinically insignificant, with QTcF <450 ms for males and <470 ms for females. If QTcF exceeds 450 ms (male) or 470 ms (female), the ECG should be repeated twice more, and the average of the three results will determine the participant's eligibility; (4) Eligible participants of reproductive potential must agree to use a medically approved contraceptive method (such as an intrauterine device, contraceptive pills, or condom) during the trial and for 6 months after the last dose, as detailed in Section 17.1, and must not plan to donate sperm/eggs during the trial and for 6 months after the last dose; (5) Participants fully understand the purpose, nature, and procedures of the trial, as well as possible adverse reactions, voluntarily agree to participate, sign a written informed consent form, and are able to comply with the protocol requirements to complete the study. Part II: Patients with Chronic HBV Infection (1) Aged 18–65 years (inclusive), any gender; (2) BMI between 18.0 and 28.0 kg/m^2 (inclusive), with male participants weighing =50 kg and female participants weighing =45 kg; (3) Chronic HBV infection with continuous stable treatment using a single nucleos(t)ide analogue (NA) for =6 months (Chronic HBV infection: clinical evidence shows HBsAg and/or HBV DNA positive for =6 months; NAs are limited to one of the following four: entecavir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, adefovir dipivoxil); stable NA treatment is defined as using a single NA for at least 6 months prior to screening without changes, and no planned changes during the trial; (4) HBeAg positive or negative at screening; (5) HBsAg between 100–5000 IU/mL (inclusive) at screening; (6) HBV DNA <10,000 IU/mL at screening; (7) Participants of reproductive potential must agree to use a medically approved contraceptive method (e.g., intrauterine device, contraceptive pills, or condoms) during the trial and for 6 months after the last dose, as detailed in section 17.1, and must not plan to donate sperm or eggs during the trial and within 6 months after the last dose; (8) Participants fully understand the purpose, nature, and procedures of the trial, as well as potential adverse reactions, voluntarily agree to participate, sign a written informed consent, and are able to comply with protocol requirements to complete the study.
Exclusion criteria
Exclusion criteria: 1. Part One: Healthy Volunteers (1) Known severe allergies, non-allergic drug reactions, or multiple drug allergies, or known hypersensitivity reactions to the investigational drug (active pharmaceutical ingredient or excipient of the formulation); (2) Individuals with clinically significant abnormal findings or diseases that need to be ruled out, including but not limited to disorders of the nervous system, cardiovascular system, hematologic and lymphatic systems, immune system, kidneys, liver, gastrointestinal tract, respiratory system, metabolism, or skeletal system, as well as those with previous health check-up indications of fatty liver with abnormal liver function; (3) Individuals testing positive for Human Immunodeficiency Virus (HIV) antibodies, HBsAg, hepatitis C antibodies, or syphilis antibodies; (4) Individuals who have had significant clinically relevant diseases or undergone major surgery (excluding minor outpatient surgery) within 3 months prior to screening, or are expected to require major surgery during the study; (5) Individuals with severe infections within 1 month prior to screening or infection symptoms within 7 days prior to screening, deemed unsuitable for participation by the investigator; (6) Individuals with a history of malignant tumors within the past 5 years (excluding cured in situ cancers, such as non-malignant melanoma or skin cancer); (7) Individuals who have used any medication (including prescription drugs, over-the-counter drugs, traditional Chinese medicine, or health supplements) within 14 days prior to first dosing (or within 5 half-lives, whichever is longer); (8) Individuals who received live vaccine administration within 1 month prior to screening; (9) Individuals who participated in any siRNA drug clinical trial and used the investigational drug within 6 months prior to screening, or participated in any other drug clinical trial and used the investigational drug within 3 months prior to screening, or plan to participate in other interventional clinical trials during this study; (10) Individuals with known or suspected history of drug abuse, or who had drug abuse within 3 months prior to screening, or tested positive in baseline drug abuse screening; (11) Malignant tumors within 5 years before screening (excluding cancers in situ that have been resected and cured, such as non-malignant melanoma skin cancer, etc.); (12) Those whose physical examination, vital signs, 12-lead electrocardiogram, and chest CT scanning results during the screening period are abnormal and clinically significant and judged by the investigator to be unsuitable for participating in this trial; (13) Poorly controlled abnormal blood pressure during the screening period (such as systolic blood pressure >=160mmHg and/or diastolic blood pressure >=100mmHg, etc.) after taking antihypertensive drugs; (14) Male participants with Fridericia's formula corrected QTcF >= 450 msec and female participants QTcF >= 470 msec (if the results of a single 12-lead ECG examination at screening show that they meet the above criteria, 2 additional 12-lead ECG measurements need to be repeated, and the average of the 3 measurements of QTcF is calculated to confirm whether the participant meets the exclusion criteria); (15) Obvious laboratory test abnormalities during the screening period, including but not limited to: 1) Alanine aminotransferase (ALT)/or Aspartate aminotransferase (AST) >=2 times the upper limit of normal (ULN); 2) Total biliru
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and Tolerability; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (time to reach peak plasma concentration, maximum plasma concentration, apparent volume of distribution in the terminal phase, apparent clearance, terminal elimination half-life, area under the plasma concentration-time curve of the test drug from 0 to time t, area under the plasma concentration-time curve of the test drug from 0 to infinity, mean residence time);PD(Results of HBsAg, HBsAb, HBeAg, HBeAb, HBcrAg, HBV DNA, and HBV RNA tests);YKYY013 Number and proportion of participants with drug-resistant antibodies, and antibody titers; | — |
Countries
China
Contacts
Public ContactDong Ruihua
Beijing Friendship Hospital ,Capital Medical University
Outcome results
None listed