Evaluate Safety and Pharmacokinetics of HLX70 in Healthy Adult Volunteers

Phase 1

Withdrawn

• Conditions: COVID 19
• Interventions: Drug: HLX70; Other: Placebo

• Registration Number: NCT04561076
• Lead Sponsor: Hengenix Biotech Inc

Brief Summary

A Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Phase I Clinical Study to Evaluate Safety and Pharmacokinetics of HLX70 in Healthy Adult Volunteers

Detailed Description

A randomized, double-blind, single-dose by intravenous administration, placebo-controlled, dose escalation, first-in-human study is proposed to evaluate the safety, PK, and immunogenicity of HLX70 in healthy subjects. The investigators plan to enroll 8 subjects in each of the 3 dose cohorts at 3 mg/kg, 10 mg/kg, and 30 mg/kg, of which 2 receive intravenous injections of placebo and 6 receive intravenous injections of the investigational product (IP). A total of 24 subjects will be enrolled.

Study Timeline

• Study First Submitted: 2020-09-07
• Study First Submitted QC: 2020-09-17
• Study First Posted: 2020-09-23
• Study Start: 2020-12-09
• Primary Completion: 2021-09-06
• Study Completion: 2021-09-18
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-20
• Last Update Posted: 2022-04-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Subjects with voluntary signing of the informed consent form (ICF);
2. Healthy males or females aged ≥ 18 and ≤ 60 years at the time of signing the ICF;
3. Subjects with body weight ≥ 50 kg and body mass index (BMI) must be higher than 18.5 kg/m2 and lower than 30 kg/m2 at screening visit;
4. Subjects who are determined to be in good health according to medical history, normal (site normal ranges to be followed) or abnormal but clinically insignificant physical examination, vital signs, ECG, laboratory test results (including hematology, serum chemistry, coagulation function, urinalysis, etc.), and investigator's clinical judgment (CTCAE grade 1 of triglycerides and uric acid is permitted). One re-test allowed per investigator discretion to confirm result.
5. Subject who agrees that he/she, and his/her spouse or partner, will use reliable contraception (see appendix 1) for 9 months after administration.

Exclusion Criteria

1. Subjects with the lab-confirmed medical history of COVID-19, including nucleic acid (PCR testing of nasopharyngeal samples) tested positive or antibody IgG/IgM tested positive.
2. Subjects with the novel onset of pyrexia/cough/shortness of breath/diarrhea or history of contact with confirmed COVID-19 individuals (positive for SARS-CoV-2 nucleic acid) within the 14 days before randomization.
3. Subjects who are known to have chronic obstructive pulmonary disease (COPD), cirrhosis of liver, cardiac failure or any condition that requires active medical intervention or monitoring to avert serious danger to the participant's health or well-being.
4. Subjects with pneumonia or tuberculosis (TB) suggested by chest X-Ray.
5. Subjects with previous exposure to a mAb or any other biological agents in 6 months before screening.
6. Subjects with previous exposure to vaccines in 3 months before screening, or who plans to receive vaccination during the study period or in 3 months after the study.
7. Subjects with previous participation in clinical trials receiving investigational drug/comparator within the longer of 30 days or 5 half-lives before screening.
8. Subjects who are known to have a history of allergy to any mAb, biological product, protein product, or the ingredient of the IP.
9. Subjects with positive test result(s) for hepatitis B virus (positive for HBsAg or positive for HBcAb and HBV-DNA), hepatitis C virus (HCV) antibodies, human immunodeficiency virus (HIV) antibodies, or treponema pallidum.
10. Subjects who are known to have a history of psychotropic drug abuse, alcoholism, or drug addiction within the last year.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Sequence 1	Placebo	Random allocation to HLX70 3 mg/kg (IV, single dose), or placebo (IV, single dose) of which 2 receive intravenous injections of placebo and 6 receive intravenous injections of the HLX70.
Sequence 2	Placebo	Random allocation to HLX70 10 mg/kg (IV, single dose), or placebo (IV, single dose) of which 2 receive intravenous injections of placebo and 6 receive intravenous injections of the HLX70.
Sequence 1	HLX70	Random allocation to HLX70 3 mg/kg (IV, single dose), or placebo (IV, single dose) of which 2 receive intravenous injections of placebo and 6 receive intravenous injections of the HLX70.
Sequence 2	HLX70	Random allocation to HLX70 10 mg/kg (IV, single dose), or placebo (IV, single dose) of which 2 receive intravenous injections of placebo and 6 receive intravenous injections of the HLX70.
Sequence 3	Placebo	Random allocation to HLX70 30 mg/kg (IV, single dose), or placebo (IV, single dose) of which 2 receive intravenous injections of placebo and 6 receive intravenous injections of the HLX70.
Sequence 3	HLX70	Random allocation to HLX70 30 mg/kg (IV, single dose), or placebo (IV, single dose) of which 2 receive intravenous injections of placebo and 6 receive intravenous injections of the HLX70.

Primary Outcome Measures

Name	Time	Method
Number of participants with adverse events, serious adverse event and infusion-related reactions as assessed by CTCAE v5.0	up to 92 days
Safety evaluation- proportion of subjects undergoing DLT events	Days 1 to 7	The proportion of subjects undergoing DLT events

Secondary Outcome Measures

Name	Time	Method
PK parameters-Maximum measured concentration	pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK parameters-Areas under the concentration-time curves	pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK parameters-Time from dosing to maximum measured concentration	pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK parameters-Volume of distribution during terminal phase and at steady state	pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK parameters-Terminal phase elimination rate constant	pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK parameters-Terminal phase elimination half life	pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK parameters-Mean residence time	pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK parameters-Clearance	pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
Anti-drug antibody	pre-infusion and Days 15, day 29, day 57, and day 92	The number of presence subjects that develop of anti-durg antibody (immunogenicity)