Evaluate the Safety, Tolerability, Pharmacodynamics, Pharmacokinetics, and Immunogenicity of HLX71 (Recombinant Human Angiotensin-converting Enzyme 2-Fc Fusion Protein for COVID-19) in Healthy Adult Subjects

NCT04583228 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: HLX71-001US-253460
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalating Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacodynamics, Pharmacokinetics, and Immunogenicity of HLX71 in Healthy Adult Subjects

Conditions

COVID 19

Outcome Measures

Primary Outcomes (2)

• Number of participants with adverse events, serious adverse event and infusion-related reactions as assessed by CTCAE v5.0

  up to 28 days

• The proportion of subjects undergoing DLT events in each dose cohorts during the DLT observation period

  Days 1 to 7

Secondary Outcomes (14)

• PK parameters-Peak concentration

  Pre-infusion, immediately post-infusion(0 hours), 1, 2.5, 4, 10, 24 hours after end of infusion and on days 3, 4, 6, 8, 10, 12, 15, 18, 22 and 29

• PK parameters-Time to peak

  Pre-infusion, immediately post-infusion(0 hours), 1, 2.5, 4, 10, 24 hours after end of infusion and on days 3, 4, 6, 8, 10, 12, 15, 18, 22 and 29

• PK parameters-Areas under the concentration-time curves

  Pre-infusion, immediately post-infusion(0 hours), 1, 2.5, 4, 10, 24 hours after end of infusion and on days 3, 4, 6, 8, 10, 12, 15, 18, 22 and 29

• PK parameters-Terminal elimination rate constant

  Pre-infusion, immediately post-infusion(0 hours), 1, 2.5, 4, 10, 24 hours after end of infusion and on days 3, 4, 6, 8, 10, 12, 15, 18, 22 and 29

• PK parameters-Elimination half-life

  Pre-infusion, immediately post-infusion(0 hours), 1, 2.5, 4, 10, 24 hours after end of infusion and on days 3, 4, 6, 8, 10, 12, 15, 18, 22 and 29

Study Arms (4)

Sequence 1

EXPERIMENTAL

Random allocation to HLX71 1 mg/kg (IV, single dose), or placebo (IV, single dose) of which 2 receive intravenous injections of placebo and 8 receive intravenous injections of the HLX71.

Drug: HLX71; Other: Placebo

Sequence 2

EXPERIMENTAL

Random allocation to HLX71 3 mg/kg (IV, single dose), or placebo (IV, single dose) of which 2 receive intravenous injections of placebo and 8 receive intravenous injections of the HLX71.

Drug: HLX71; Other: Placebo

Sequence 3

EXPERIMENTAL

Random allocation to HLX71 10 mg/kg (IV, single dose), or placebo (IV, single dose) of which 2 receive intravenous injections of placebo and 8 receive intravenous injections of the HLX71.

Drug: HLX71; Other: Placebo

Sequence 4

EXPERIMENTAL

Random allocation to HLX71 15 mg/kg (IV, single dose), or placebo (IV, single dose) of which 2 receive intravenous injections of placebo and 8 receive intravenous injections of the HLX71.

Drug: HLX71; Other: Placebo

Interventions

HLX71 DRUG

Single-dose, intravenous infusion

Also known as: Recombinant Human Angiotensin-Converting Enzyme 2-Fc Fusion Protein

Sequence 1; Sequence 2; Sequence 3; Sequence 4

Placebo OTHER

Single-dose, intravenous infusion

Sequence 1; Sequence 2; Sequence 3; Sequence 4

Eligibility Criteria

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

You may qualify if:

• Subjects with voluntary signing of the informed consent form (ICF), and capable of understanding and following the requirements.
• Healthy males or females aged ≥ 18 and \< 65 years at the time of signing the ICF.
• Body weight ≥ 50.0 kg and \< 100.0 kg, and body mass index (BMI) ≥ 18.5 kg/m2 and \< 30.0 kg/m2.
• The subject is in good health as determined by the Investigator according to medical history, physical examination, vital signs, 12-lead ECG, chest X-ray, and laboratory tests (hematology, serum chemistry, C-reactive protein, thyroid function, coagulation, etiology, urinalysis).
• No plan of pregnancy and being willing to use continuous effective contraception for subjects (including partner) from informed consent to 6 months after administration of investigational product, see Appendix 1 for the specific contraceptive measures.

You may not qualify if:

• Subjects with the lab-confirmed medical history of COVID-19, including SARS-CoV-2 determined by reverse transcription-polymerase chain reaction (RT-PCR) or positive specific antibody IgM or IgG against serum SARS-CoV-2.
• Subjects with the novel onset of pyrexia/cough/shortness of breath/diarrhea or history of contact with confirmed COVID-19 individuals within the 14 days before randomization.
• Pneumonia or active tuberculosis (TB) indicated by chest X-Ray, or abnormal and clinically significant as judged by the Investigator.
• Abnormal blood pressure or pulse rate: systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg, SBP ≤ 90 mmHg or DBP \< 60 mmHg, pulse rate \< 50 beats /min or \> 100 beats/min at screening and clinically significant as judged by the Investigator.
• Clinically significant 12-lead ECG abnormalities, or QTcF interval \> 450 msec at screening, or history of clinically significant ECG abnormalities, which may increase the risk to the subject as judged by the Investigator.
• Use of monoclonal antibodies or fusion proteins within 6 months before screening.
• 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.
• History of allergy to any monoclonal antibody, fusion protein, biological product, protein product, or ingredient of the IP.
• Family history of cardiovascular disease, history of atherosclerosis, presence of chronic obstructive pulmonary disease (COPD), cirrhosis, cardiovascular disease, or any condition that requires active medical intervention or monitoring to avert serious danger to the participant's health or well-being.
• History of blood loss or blood donation (including blood component donation) ≥ 400 mL, or reception of blood transfusion within 3 months prior to screening; blood loss or donation (including blood component donation) ≥ 200 mL within 1 month prior to screening.
• Previous surgery within 2 months before screening, or scheduled surgery during the study.
• Previous administration of any investigational drugs/comparators in clinical trials within 3 0 days or remaining in the elimination period of the drug (within 5 half-lives) before screening, or still in the follow-up period of a certain clinical study.
• Use of prescribed drugs, over-the-counter (OTC) drugs, or herbal medicines (excluding vitamins and mineral supplements) within 14 days before screening.
• History of alcohol abuse or intake of excessive alcohol in the past 6 months (15 unit of alcohol per week: 1 unit = 285 mL beer, or 25 mL liquor, or 100 mL wine), or alcohol breath test positive, or unwilling/unable to quit alcohol drinking during the study.
• Subjects who smoke ≥ 5 cigarettes per day or are positive in tobacco screening , or those who are unwilling/unable to quit nicotine intake during the study.

Sponsors & Collaborators

• Hengenix Biotech Inc: lead

Study Sites (1)

Frontage Clinical Services, Inc.

Secaucus, New Jersey, 07094, United States

Location

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Frank Lee, MD

  Frontage Clinical Services, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A total of 32 subjects were randomized in a double blind fashion with 24 subjects receiving active drug and 8 subjects receiving placebo. Eight subjects were randomized in each dose cohort at a 3:1 ratio, with 6 subjects receiving active drug and 2 subjects receiving placebo.
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The investigators plan to enroll 8 subjects in each sequence, of which 2 receive intravenous injection of placebo and 6 receive intravenous injection of IP. Subjects are allocated in two groups randomly.

Study Record Dates

• First Submitted: September 25, 2020
• First Posted: October 12, 2020
• Study Start: April 8, 2021
• Primary Completion: July 15, 2021
• Study Completion: July 20, 2021
• Last Updated: April 1, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)