Safety, Tolerability, Pharmacokinetics(PK), Pharmacodynamics(PD) and Food Effect of HRS9950 in Healthy and CHB Subjects

NCT04464733 | Completed Phase 1

• 1 other identifier: HRS9950-101
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a randomized, Double-Blind, Placebo-Controlled study to evaluate the safety, tolerability and pharmacokinetics, pharmacodynamics and food effect of HRS9950. The study will be conducted in three parts sequentially: Part 1, evaluate the safety, tolerability and pharmacokinetics, pharmacodynamics of single doses and multiple dose of HRS9950 tablet in healthy subjects. Part 1 will consist of 84 healthy subjects, 8 groups.There will be 14 subjects in 0.75mg dose group,10 subjects in each other dose group . Part 2, evaluate food effect of HRS9950 in healthy subjects. Part 2 will consist of 14 healthy subjects, 1 group (one of groups in Part 1). Part 3, evaluate the safety, tolerability and pharmacokinetics, pharmacodynamics of multiple doses of HRS9950 tablet in naive and treatment-experienced chronic hepatitis B (CHB) patients. Part 3 will consist of 60 CHB patients, 1 group for naive patients and 5 groups for treatment-experienced patients.

Conditions

Chronic Hepatitis b

Outcome Measures

Primary Outcomes (9)

• The incidence and severity of treatment-related adverse events as assessed by CTCAE v5.0

  8 DAYS for Group A-M; 29 DAYS for Group F; 50 DAYS for Group G-O

• Maximum Plasma Concentration [Cmax]

  Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma

  0-48 hours after each dose for Group A-E、K-M；Group F- J、N、O at Day 1 and Day 22

• Area under the concentration time curve [AUC]

  Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma

  0-48 hours after each dose for Group A-E、K-M；Group F- J、N、O at Day 1 and Day 22

• Time to maximum plasma concentration [Tmax]

  Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma

  0-48 hours after each dose for Group A-E、K-M；Group F- J、N、O at Day 1 and Day 22

• Apparent clearance [CL/F]

  Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma

  0-48 hours after each dose for Group A-E、K-M；Group F- J、N、O at Day 22

• Half-time [t1/2]

  Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma

  0-48 hours after each dose for Group A-E、K-M；Group F- J、N、O at Day 22

• Apparent volume of distribution [Vz/F（Vd）]

  Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma

  0-48 hours after each dose for Group A-E、K-M；Group F- J、N、O at Day 22

• Mean residence time [MRT]

  Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma

  0-48 hours after each dose for Group A-E、K-M；Group F- J、N、O at Day 22

• The concentration of IL-12p40 in the serum

  After single or multiple administration of HRS9950

  0-48 hours after each dose for Group A-E、G-O

Study Arms (15)

Treatment group A

EXPERIMENTAL

single dose

Drug: HRS9950; Drug: Placebo

Treatment group B

EXPERIMENTAL

single dose

Drug: HRS9950; Drug: Placebo

Treatment group C

EXPERIMENTAL

single dose; food effect

Drug: HRS9950; Drug: Placebo

Treatment group D

EXPERIMENTAL

single dose

Drug: HRS9950; Drug: Placebo

Treatment group E

EXPERIMENTAL

single dose

Drug: HRS9950; Drug: Placebo

Treatment group F

EXPERIMENTAL

multiple doses

Drug: HRS9950; Drug: Placebo

Treatment group G

EXPERIMENTAL

multiple doses

Drug: HRS9950; Drug: Placebo

Treatment group H

EXPERIMENTAL

multiple doses

Drug: HRS9950; Drug: Placebo

Treatment group I

EXPERIMENTAL

multiple doses

Drug: HRS9950; Drug: Placebo

Treatment group J

EXPERIMENTAL

multiple doses

Drug: HRS9950; Drug: Placebo

Treatment group K

EXPERIMENTAL

single dose

Drug: HRS9950; Drug: Placebo

Treatment group L

EXPERIMENTAL

single dose

Drug: HRS9950; Drug: Placebo

Treatment group M

EXPERIMENTAL

single dose

Drug: HRS9950; Drug: Placebo

Treatment group N

EXPERIMENTAL

multiple doses

Drug: HRS9950; Drug: Placebo

Treatment group O

EXPERIMENTAL

multiple doses

Drug: HRS9950; Drug: Placebo

Interventions

HRS9950 DRUG

HRS9950

Treatment group A; Treatment group B; Treatment group C; Treatment group D; Treatment group E; Treatment group F; Treatment group G; Treatment group H; Treatment group I; Treatment group J; Treatment group K; Treatment group L; Treatment group M; Treatment group N; Treatment group O

Placebo DRUG

Placebo

Treatment group A; Treatment group B; Treatment group C; Treatment group D; Treatment group E; Treatment group F; Treatment group G; Treatment group H; Treatment group I; Treatment group J; Treatment group K; Treatment group L; Treatment group M; Treatment group N; Treatment group O

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy subjects
• Signed informed consent.
• Aged 18\~55.
• Body weight ≥ 50 kg for male; ≥ 45 kg for female, body mass index (BMI) between 18 to 28 kg/m2.
• Vital signs, physical examination, laboratory results are within normal range or considered not clinically significant.
• Female subjects (including partner) of childbearing potential must be using a medically acceptable form of birth control.
• CHB subjects
• Signed informed consent.
• Aged 18\~65.
• CHB subjects should meet the following two criteria:
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• IgM HBcAb negative and HBsAg positive.
• Two recorded HBsAg positive, and the time interval between the two tests was at least 6 months, one of which was the result of this screening 4. Treatment-experienced CHB subjects should also meet the following criteria:
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• Have received nucleoside analogue treatment for at least 6 months

You may not qualify if:

• Healthy subjects
• Currently suffering from cardiovascular, liver, kidney, digestive, nervous, blood, thyroid or mental diseases.
• Medical history of malignant tumor.
• Have a digestive system disease or a medical history of severe digestive system disease.
• Have severe infection, severe trauma or major surgical operations within 3 months.
• ECG test have clinical significant abnormality or the QT interval (QTc) \> 450 ms.
• Clinical laboratory examinations or chest radiographs have clinical significant abnormality.
• Have a medical history of immune-mediated diseases.
• Screening for infectious diseases is positive (Including HBsAg, Anti-HCV, TPPA, Anti-HIV).
• Suspected allergy to any ingredient in the study drug.
• Have any drug that inhibits or induces liver metabolism within 1 month.
• Take any prescription drugs, over-the-counter drugs and Chinese herbal medicines within 14 days before taking the study drug, or took any drugs within 5 half-lives at the time of screening; plan to take other drugs during the test period.
• Participated in clinical trials of any drug or medical device within 3 months before screening, or within 5 half-lives before screening.
• Had donated blood or blood transfusion in 8 weeks or ≥ 400 mL within 3 months prior to screening or ≥ 200 mL within 1 months.
• The average daily smoking ≥ 5 cigarettes within three months; the average daily alcohol intake in a month exceeds 15 g (15 g alcohol is equivalent to 450 mL beer or 150 mL wine or 50 mL low-alcohol);

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

Beijing Youan Hospital,Capital Medical University

Beijing, Beijing Municipality, 100069, China

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2020
• First Posted: July 9, 2020
• Study Start: July 20, 2020
• Primary Completion: May 30, 2023
• Study Completion: May 30, 2023
• Last Updated: November 5, 2024

Record last verified: 2024-11

Locations

CN (1)