Study of Pharmacokinetics, Pharmacodynamics, Safety, and Immunogenicity of of HZBio1 in Healthy Subjects

A Study to Investigate the Pharmacokinetics, Safety, Tolerability and Immunogenicity of HZBio1 in Healthy Chinese Volunteers

This randomized study will evaluate the safety, tolerability ,pharmacokinetics, pharmacodynamics and Immunogenicity of single ascending intramuscularly administered doses of HZBio1 in healthy volunteers.

Study Overview

• Status: Unknown
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: HZBio1 0.96mg / kg; Drug: Placebo; Drug: HZBio1 3mg / kg; Drug: HZBio1 6mg / kg; Drug: HZBio1 9mg / kg; Drug: HZBio1 12mg / kg

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Peking, China
    • Peking Union Medical College Hospital
    • Contact: Hongzhong Liu, bachelor; Phone Number: 010-69158364; Email: liuhzpumch@126.com
    • Principal Investigator: Hongzhong Liu, bachelor
    • Principal Investigator: Xin Zheng, doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Fully informed and signed informed consent form;
2. Healthy subjects, male and female;

3. At the time of signing the informed consent, they were over 18-45 years old (including 18 and 45 years old) and weighed more than 50 kg,

   Body mass index ranged from 19 to 26 (including 19 and 26) [body mass index (BMI) = body weight (kg) / height 2 (M2)];

4. The results of serum pregnancy test in women of childbearing age were negative;
5. The subjects agreed to use effective contraception or abstinence during the study period and within 6 months after the end of the study;
6. Be able to understand and comply with the clinical protocol requirements, and it is expected to complete the whole trial process.

Exclusion Criteria:

1. History of hypertension or abnormal blood pressure at screening / baseline (SBP > 140 mmHg and / or DBP > 90 mmHg confirmed twice a day)
2. According to the researcher's judgment (clinical urine routine examination, proteinuria 2 + and above), proteinuria or proteinuria history with clinical significance.
3. Any previous VEGF and VEGFR antibody or protein therapy within one year.
4. No biological products or live virus vaccine shall be used for treatment for 3 months before the first administration of the study drug, or any monoclonal antibody shall be used for 12 months.
5. History or evidence of hereditary bleeding, coagulopathy, or thrombosis.
6. History of gastrointestinal perforation or fistula.
7. Severe, unhealed wounds, active ulcers, or untreated fractures, or were randomly assigned or expected to require major surgery during the course of the study or within 2 months after the last administration of the study drug.
8. RX or OTC drugs or nutritional supplements were used within 5 half lives before the first administration of the study drug or within 2 weeks (depending on the longer period). Herbal supplements need to be discontinued 28 days before the first administration of the study drug.
9. HBsAg, HCV antibody, HIV antibody and syphilis were positive
10. Known allergy to bevacizumab or any excipient
11. Known allergic diseases or allergic constitution
12. There was a history of unpaid blood donation within 3 months before taking the study drug for the first time
13. Use any other study drug for treatment or participate in other clinical trials within 3 months before screening
14. There was a history of alcohol or drug abuse within 12 months before screening; subjects were not able to control within 72 hours before and throughout the study
15. History of mental illness
16. During the study, the partner was expected to be pregnant.
17. During the study period, it did not conform to the clinical study protocol.
18. Other conditions not suitable for this study were considered by the researchers

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: HZBio1 0.96mg/kg; Participants will receive intramuscularly 0.96 milligram per kilogram (mg/kg) of HZBio1.	Drug: HZBio1 0.96mg / kg; HZBio1 will be administered intramuscularly in single ascending doses with starting of 0.96 mg/kg and subsequent doses of 3.0 mg/kg, 6.0 mg/kg ,9.0 mg/kg,and 12mg/kg, respectively.; Drug: Placebo; Matching placebo will be administered intramuscularly.
EXPERIMENTAL: HZBio1 3mg/kg; Participants will receive intramuscularly 3 milligram per kilogram (mg/kg) of HZBio1.	Drug: Placebo; Matching placebo will be administered intramuscularly.; Drug: HZBio1 3mg / kg; HZBio1 will be administered intramuscularly in single ascending doses with starting of 0.96 mg/kg and subsequent doses of 3.0 mg/kg, 6.0 mg/kg ,9.0 mg/kg,and 12mg/kg, respectively.
EXPERIMENTAL: HZBio1 6mg/kg; Participants will receive intramuscularly 6 milligram per kilogram (mg/kg) of HZBio1.	Drug: Placebo; Matching placebo will be administered intramuscularly.; Drug: HZBio1 6mg / kg; HZBio1 will be administered intramuscularly in single ascending doses with starting of 0.96 mg/kg and subsequent doses of 3.0 mg/kg, 6.0 mg/kg ,9.0 mg/kg,and 12mg/kg, respectively.
EXPERIMENTAL: HZBio1 9mg/kg; Participants will receive intramuscularly 9milligram per kilogram (mg/kg) of HZBio1.	Drug: Placebo; Matching placebo will be administered intramuscularly.; Drug: HZBio1 9mg / kg; HZBio1 will be administered intramuscularly in single ascending doses with starting of 0.96 mg/kg and subsequent doses of 3.0 mg/kg, 6.0 mg/kg ,9.0 mg/kg,and 12mg/kg, respectively.
EXPERIMENTAL: HZBio1 12mg/kg; Participants will receive intramuscularly 12 milligram per kilogram (mg/kg) of HZBio1.	Drug: Placebo; Matching placebo will be administered intramuscularly.; Drug: HZBio1 12mg / kg; HZBio1 will be administered intramuscularly in single ascending doses with starting of 0.96 mg/kg and subsequent doses of 3.0 mg/kg, 6.0 mg/kg ,9.0 mg/kg,and 12mg/kg, respectively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events (AEs)	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	36 days
Tmax of HZBio1	Time to peak (Tmax)	36 days
Cmax of HZBio1	peak concentration (Cmax)	36 days
Кel of HZBio1	Кel of HZBio1 (elimination constant)	36 days
Т1/2 of HZBio1	Т1/2 of HZBio1 (half-life)	36 days
AUC0-t of HZBio1	AUC0-t of HZBio1 (the area under the Concentration vs. Time curve from 0 to t post-infusion)	36 days
serum uric acid level	The decrease of serum uric acid level after administration will be analyzed.	36 days
Number of Participants Positive for Nab（Neutralizing Antibody）	The changes of neutralizing antibody were observed before and after treatment.	36 days
Number of anti peg antibody	The changes of anti peg antibody were observed before and after treatment.	36 days
Number of anti PHC antibody	The changes of anti PHC antibody were observed before and after treatment.	36 days

Collaborators and Investigators

• Sponsor: Hangzhou Grand Biologic Pharmaceutical, Inc.
• Collaborators: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Xin Zheng, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 1, 2021
• Primary Completion (ANTICIPATED): October 31, 2021
• Study Completion (ANTICIPATED): December 31, 2021

Study Registration Dates

• First Submitted: January 12, 2021
• First Submitted That Met QC Criteria: February 18, 2021
• First Posted (ACTUAL): February 23, 2021

Study Record Updates

• Last Update Posted (ACTUAL): March 1, 2021
• Last Update Submitted That Met QC Criteria: February 24, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: YDHY（HZBio1）-001（I）

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No