Compare Pharmacokinetic, Safety, Tolerability and Immunogenicity of HLX12 and Ramucirumab in Healthy Male Adult Subjects

A Randomized, Parallel-controlled, Intravenous Single-dose, Phase I Clinical Study Comparing the Pharmacokinetic Profile, Safety, Tolerability and Immunogenicity of HLX12 and Cyramza (Ramucirumab) in Healthy Male Adult Subjects

The study consists of 2 parts:

Part I study: to preliminarily compare the PK profile of HLX12 and Cyramza This study is an open-label, randomized, parallel-controlled, intravenous single-dose pretrial study comparing the pharmacokinetic profile, safety, tolerability and immunogenicity of HLX12 and Ramucirumab in healthy male adult subjects. The number of subjects is set to 24, who will be randomized into two groups, and each group has the same number of subjects (n=12). Group 1 will receive intravenous infusion of the test preparation T HLX12, while Group 2 will receive Cyramza, once in both groups.

Part II study: to compare the PK similarity between HLX12 and Cyramza This study is a randomized, double-blind, parallel-controlled, intravenous single-dose Phase I clinical study comparing the pharmacokinetic profile, safety, tolerability and immunogenicity of HLX12 and Ramucirumab in healthy male adult subjects.The number of subjects is set to 128, and the treatment is the same with Part I study.

Study Overview

• Status: Terminated
• Conditions: Healthy Male Volunteers
• Intervention / Treatment: Biological: HLX12; Biological: Cyramza (Ramucirumab)

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China
      • First Hospital of Jilin University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Healthy adult male aged 18-50 years (including 18 and 50 years old) with a body mass index of 18-28 kg/m2 (including 18 kg/m2 and 28 kg/m2), weighing ≥50 kg and ≤80 kg;

Exclusion Criteria:

Previous or current atopic allergies, hypersensitivity reactions, or allergic reactions that are clinically significant, including known or suspected clinically relevant drug allergies to a component of the study drug or the control drug; Any disease that may affect the safety of the subject or affect the study operation and assessment, according to the investigator's judgment; Have undergone surgery in the past 8 weeks, or are planned for surgery during the study period; Have been inoculated with live virus vaccine within 4 weeks prior to screening, or intend to be inoculated with live virus vaccine during the study period until the end of the last follow-up; Any prior history of exposure to anti-VEGF or anti-VEGF receptor monoclonal antibodies/proteins; Exposure to any monoclonal antibody within 12 months prior to study drug administration; Have used any clinical study drug within 3 months prior to screening, or are still in the follow-up period of a clinical study; Have taken non-steroidal anti-inflammatory drugs (NSAIDs) within 14 days prior to the study drug administration, including any dose of aspirin. NSAIDs (except acetaminophen) shall not be used during the study; QTc interval > 450 ms; ECG is abnormal and the abnormality is clinicaly significant as judged by the investigator; Have taken any alcoholic products within 48 hours prior to the study drug administration; Subjects who have a family history of hypertension, or are found with abnormal blood pressure at screening or on admission to the study site (Day-1): systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, which is judged by the investigator as clinically significant ; Have a genetic predisposition to bleeding or thrombosis, or a history of bleeding due to non-trauma (ie, bleeding requiring medical intervention), a thromboembolic event, or any condition that may increase the risk of bleeding, including coagulopathy, thrombocytopenia (platelet count <100*109/L) or international normalized ratio (INR) higher than 1.5;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: HLX12 group; HLX12 are given intravenous infusion 8 mg/kg, prepared with normal saline to an administration volume of 250 mL, and the administration time is 90 min (± 10 min).	Biological: HLX12; healthy volunters receive HLX12 (8mg/kg) once
ACTIVE_COMPARATOR: Cyramza (Ramucirumab) group; Ramucirumab are given intravenous infusion of Cyramza 8 mg/kg, prepared with normal saline to an administration volume of 250 mL, and the administration time is 90 min (± 10 min).	Biological: Cyramza (Ramucirumab); healthy volunters receive Cyramza (Ramucirumab) 8mg/kg once

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0~inf	Area under curve from zero to infinity	from predose to 1680 hours (Day 71),18 timepoints

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety and tolerability of two groups	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	from day1 to day 71
safety and tolerability of two groups	Number of AE as assessed by CTCAE v5.0	from day1 to day 71
safety and tolerability of two groups	AE listing as assessed by CTCAE v5.0	from day1 to day 71
AUC0~t	area under the concentration-time curve	from predose to 1680 hours (Day 71),18 timepoints
Cmax	maximum concentration	from predose to 1680 hours (Day 71),18 timepoints

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech
• Investigators: Principal Investigator: Yanhua Ding, First Hospital of Jinlin University

Publications and helpful links

General Publications

• American Society for Clinical Pharmacology and Therapeutics. Clin Pharmacol Ther. 2022 Mar;111 Suppl 1:S5-S80. doi: 10.1002/cpt.2521. No abstract available. Erratum In: Clin Pharmacol Ther. 2022 Apr 17;:1344.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 6, 2019
• Primary Completion (ACTUAL): September 24, 2019
• Study Completion (ACTUAL): September 24, 2019

Study Registration Dates

• First Submitted: February 25, 2019
• First Submitted That Met QC Criteria: March 3, 2019
• First Posted (ACTUAL): March 5, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 10, 2022
• Last Update Submitted That Met QC Criteria: May 5, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Ramucirumab
• Other Study ID Numbers: HLX12-001

Drug and device information, study documents

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