Pharmacokinetic, Safety and Immunogenicity Phase I Study of HLX04 Versus Avastin® in Healthy Male Subjects

NCT03483649 | Completed Phase 1 FDA Drug

• 1 other identifier: HLX04 HV01
• Study Type: interventional
• Target: 208
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I, randomized, double blind, IV, single dose, 4-arm parallel study to compare the PK, and to evaluate the safety, tolerability and immunogenicity of HLX04, US Avastin®, EU Avastin®, and CN Avastin® in healthy male subjects.

Conditions

Healthy Male Subjects

Outcome Measures

Primary Outcomes (2)

• AUC(0-t)

  Area under the concentration time curve of the analyte in serum over the time interval from 0 to the last quantifiable concentration at time "t" \[AUC(0-t)\]

  from 0 to day 99

• AUC(0-∞)

  Area under the concentration time curve of the analyte in serum over the time interval from 0 extrapolated to infinity \[AUC(0-∞)\]

  from 0 to day 99

Secondary Outcomes (9)

• Cmax

  from 0 to day 99

• TEAE and SAE

  from 0 to day 99

• tmax

  from 0 to day 99

• t1/2

  from 0 to day 99

• λz

  from 0 to day 99

Study Arms (4)

HLX04

EXPERIMENTAL

Drug: HLX04

United States (US) Avastin®

ACTIVE COMPARATOR

Drug: US-Avastin®

European Union (EU) Avastin®

ACTIVE COMPARATOR

Drug: EU-Avastin®

China (CN) Avastin®

ACTIVE COMPARATOR

Drug: CN-Avastin®

Interventions

HLX04 DRUG

HLX04: Supplied as 100 mg/4 mL solution; reconstituted to 100 mL with 0.9% sodium chloride; a single dose of 3 mg/kg will be administered intravenously for 90 minutes.

HLX04

US-Avastin® DRUG

US Avastin®: Supplied as 100 mg/4 mL solution; reconstituted to 100 mL with 0.9% sodium chloride; a single dose of 3 mg/kg will be administered intravenously for 90 minutes.

United States (US) Avastin®

EU-Avastin® DRUG

EU-Avastin®: Supplied as 100 mg/4 mL solution; reconstituted to 100 mL with 0.9% sodium chloride; a single dose of 3 mg/kg will be administered intravenously for 90 minutes.

European Union (EU) Avastin®

CN-Avastin® DRUG

CN-Avastin®: Supplied as 100 mg/4 mL solution; reconstituted to 100 mL with 0.9% sodium chloride; a single dose of 3 mg/kg will be administered intravenously for 90 minutes.

China (CN) Avastin®

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects who are willing to comply with the contraception restrictions for this study (see Section 4.3.3).
• Subjects who are able and willing to give written informed consent.
• Subjects who are willing to comply with the study restrictions from screening until end of study.
• Adult males aged 18 to 50 years inclusive and between 19 and 26 kg/m2 body mass index and body weight ≥ 50 kg and ≤ 80 kg.
• Subjects who are non smokers or have not used tobacco or nicotine containing products for at least 3 months preceding screening and have less than 5 cigarettes per day smoking history. Subjects must agree to refrain from smoking during days of confinement at the study center.
• Subjects negative for Hepatitis B surface antigen, Hepatitis C virus antibody, Treponema pallidum antibody, and human immunodeficiency virus antibody tests.
• Subjects negative for urine drug screen and alcohol tests.
• Subjects determined healthy by medical history, physical examination, laboratory tests, 12 lead electrocardiogram (ECG), and chest X ray, without any clinically significant abnormality judged by the Investigator.

You may not qualify if:

• History of gastrointestinal, endocrine, pulmonary, hepatic, renal, psychiatric, neurological, cardiovascular, hematological, and metabolic (including known diabetes mellitus) disease or disorder considered as significant by the Investigator.
• History of any cancer, lymphoma, or leukemia, except basal cell carcinoma of skin after localized cancer is removed.
• History or current clinically significant atopic allergy, hypersensitivity or allergic reactions including known or suspected clinically relevant drug hypersensitivity to any component of the study drug formulations or comparable drugs.
• Any disorder that, in the Investigator's opinion, may interfere with the safety of the subject and the study procedures and evaluations.
• Blood loss or blood donation (including blood components donation) ≥ 400 mL or blood transfusion within 3 months before screening; blood loss or blood donation (including blood components donation) ≥ 200 mL within 1 months before screening.
• Surgery within the past 8 weeks or surgery planned during the study duration.
• Poor oral hygiene that may require surgical intervention during the study or any planned dental interventions during the study duration.
• Live virus vaccination within 4 weeks prior to screening or intention to receive live virus vaccination during the study until the final follow up visit.
• History of prior exposure to bevacizumab or any anti VEGF or anti VEGF receptor (VEGFR) monoclonal antibodies or proteins (e.g., aflibercept, ramucirumab, lapatinib, and sunitinib).
• Prior exposure to any other investigational monoclonal antibody within 12 months of study drug administration.
• Use of any investigational drug in any clinical study within the 3 months prior to first dose administration in this study; or remains on follow up of any clinical study.
• Any intake of a non steroidal anti inflammatory drug (NSAID) including any dose of aspirin in the last 14 days. NSAIDs are not allowed for the duration of the study. Paracetamol is allowed for pain control if required.
• Intake of prescribed or over the counter drugs within 28 days of study drug administration or herbal drugs or dietary supplements within 28 days prior to study drug administration.
• Any persons who are:
• An employee of the Principal Investigators, study centers, contract research organization (CRO) or the Sponsor.

Sponsors & Collaborators

• Shanghai Henlius Biotech: lead

Study Sites (1)

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Related Publications (1)

• Zhu X, Qian H, Sun J, Wu M, Yu C, Ding Y, Zhang X, Chai K, Li X. A phase 1 randomized study compare the pharmacokinetics, safety and immunogenicity of HLX04 to reference bevacizumab sourced from the United States, the European Union, and China in healthy Chinese male volunteers. Cancer Chemother Pharmacol. 2021 Sep;88(3):465-474. doi: 10.1007/s00280-021-04297-z. Epub 2021 Jun 4.

  PMID: 34086067 DERIVED

Related Links

• Related Info

Study Officials

• Yanhua Ding, M.D.

  The First Hospital of Jilin University

  PRINCIPAL INVESTIGATOR

• Chen Yu, M.D.

  Shanghai Xuhui Central Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 30, 2017
• First Posted: March 30, 2018
• Study Start: April 21, 2017
• Primary Completion: October 29, 2017
• Study Completion: October 29, 2017
• Last Updated: May 11, 2022

Record last verified: 2022-05

Locations

CN (1)