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Phase I Study of HLX3 vs Adalimumab in Chinese Healthy Subjects

Primary Purpose

Immune System Disorder

Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
HLX03
adalimumab
Sponsored by
Shanghai Henlius Biotech
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Immune System Disorder focused on measuring HLX03, adalimumab, pharmacokinetics, biosimilar

Eligibility Criteria

18 Years - 45 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

  1. Healthy Chinese males (age: 18~45 yrs) with contraception during and 3 months post-dose. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination including blood pressure, pulse, ECG, and laboratory testing.
  2. BMI between 19.0 and 28.0 kg/m² and body weight between 55 kg and 80 kg.

Exclusion Criteria:

  1. suffering from active or latent tuberculosis or history of tuberculosis;
  2. have heart disease or a history of heart disease;
  3. suffer from mental illness or psychiatric history;
  4. suffering from malignant tumors and their history;
  5. suffering from herpes zoster and its history;
  6. suffering from epilepsy and history of epilepsy;
  7. be allergic to the drugs or its components with high sensitivity or allergic reaction, detection of ADA (+);
  8. patients who lost blood or donated more than 200 mL within the first 2 months before the screening;
  9. major surgery performed within 30 days prior to signing ICF;
  10. live vaccine inoculation or vaccination within 12 weeks of screening, or possible administration of vaccine during screening and study visits;
  11. previous application of adalimumab or its biosimilars, or anti-TNF alpha drugs;
  12. participating in other clinical trials within the first 3 months of the trial;
  13. abnormal immune function within 4 weeks before screening;
  14. the presence of invasive systemic fungal infection or other opportunistic infections within 2 months prior to screening;
  15. systemic or local infection, such as the risk of sepsis and / or known active inflammation within 2 months before screening;
  16. 2 months before the screening, there were severe infections in the hospital and / or the need for intravenous antibiotics;
  17. 4 or more upper respiratory tract infections occurred within 6 months prior to randomization;
  18. hepatitis B surface antigen (HBsAg) positive; if hepatitis B surface antigen (HBsAg) negative, hepatitis B core antibody (HBcAb) positive, peripheral blood hepatitis B virus deoxyribonucleic acid (DNA) test >0 IU/ml also ruled out;
  19. hepatitis C virus (HCV) antibody positive;
  20. human immunodeficiency virus (HIV) antibody positive;
  21. Treponema pallidum (Treponema pallidum, TP) antibody positive;
  22. anti nuclear antibody titer was 1:100 examination;
  23. drug abusers, alcohol addicts;
  24. , the researchers discretion of failure to follow the requirements of the program, instructions and research limitations, such as uncooperative attitude, unable to return to the Research Center for follow-up visits, or unable to complete the entire clinical study.

Sites / Locations

  • the 1st affiliated hospital of Jilin University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

HLX03

Humira

Arm Description

There are about 68 subjects in this group will receive a single dose of 40 mg of HLX03 in 0.8 mL in subcutaneous injection.

There are about 68 subjects in this group will receive a single dose of 40 mg of Humira in a pre-filled syringe in subcutaneous injection.

Outcomes

Primary Outcome Measures

Maximum Concentration（Cmax） of Adalimumab After Single SC Injection of HLX03/Humira
Area Under the Plasma Concentration-time Curve From Zero (0) Hours to the last quantifiable concentration

Secondary Outcome Measures

Area Under the Plasma Concentration-time Curve From Zero (0) to Time Infinity
Time to Maximum Concentration（Tmax） of Adalimumab After Single SC Injection
Half-life time of adalimumab after single SC injection of HXL03/Humira

Full Information

First Posted
November 26, 2017
Last Updated
May 4, 2022
Sponsor
Shanghai Henlius Biotech
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1. Study Identification

Unique Protocol Identification Number
NCT03357939
Brief Title
Phase I Study of HLX3 vs Adalimumab in Chinese Healthy Subjects
Official Title
A Phase 1 Randomized,Double-Blind and Parallel Controlled Single-dose Clinical Trial of Pharmacokinetics, Safety, Tolerability and Immunogenicity of HLX03 Compared With Humira® From China Source in Chinese Healthy Male Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
January 12, 2017 (Actual)
Primary Completion Date
September 15, 2018 (Actual)
Study Completion Date
September 15, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Henlius Biotech

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This healthy male volunteers study will evaluate 148 subjects who will receive a single sub-cutaneous dose of HLX03 （a monoclonal antibody against TNF-a, 40 mg/ 0.8 mL） or Adalimumab(Humira,China spourced,40 mg/0.8 mL injection with a single-use prefilled syringe). This study will involve sampling,pharmacokinetics, safety, tolerability and immunogenicity evaluation of drug levels following administration of HLX03 and the licensed adalimumab products.
Detailed Description
This is a randomized, doubl-blinded, parellel-controlled phase 1 PK, safety, tolerability and immunogenicitiy study to compare HLX03, designed as an Adalimumab biosimilar, with China sourced Humira in Chinese health volunteers. All enrolled subjects will receive a single dose of HLX03 (40 mg）or Humira(adalimumab, 40 mg) in subcutaneous injectioin after randomization. The purpose of this study to prove the similarity in PK, Safety, tolerability and immunogenicity beween HLX03（adalimumab biosimilar） and China sourced Humira and provide evidence for Phase III comparison study. The blood will be collected before drug administration, and at 1 hr、4 hr、8 hr、24 hr (1d)、48 hr (2d)、72 hr (3d)、96 hr (4d)、、144 hr (6d)、192 hr (8d)、240 hr (10d)、 336 hr (14d)、504 hr (21d)、672 hr (28d)、840 hr (35d)、1008 hr (42d)、1176 hr (49d)、1344 hr (56d)、1680 hr (70d) after drug injection for PK, ADA, etc analysis. All subjects also will be followed up at 0, 1,2,3,4,6,8,10,14,21,28,35, 42, 49, 56, and 70 days after drug administration for AE and other specified outcomes. The main endpoint is AUC from time zero to ∞. The second endpoints include Cmax, Tmax, T1/2, CL, Vd and AUC（0-last）. This is single center study in China.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Immune System Disorder
Keywords
HLX03, adalimumab, pharmacokinetics, biosimilar

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
220 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HLX03
Arm Type
Experimental
Arm Description
There are about 68 subjects in this group will receive a single dose of 40 mg of HLX03 in 0.8 mL in subcutaneous injection.
Arm Title
Humira
Arm Type
Active Comparator
Arm Description
There are about 68 subjects in this group will receive a single dose of 40 mg of Humira in a pre-filled syringe in subcutaneous injection.
Intervention Type
Drug
Intervention Name(s)
HLX03
Other Intervention Name(s)
adalimumab biosimilar
Intervention Description
A single dose of 40 mg HLX03 in 0.8 mL in subcutaneous injection.
Intervention Type
Drug
Intervention Name(s)
adalimumab
Other Intervention Name(s)
Humira
Intervention Description
A single dose of 40 mg Humira in 0.8 mL in a pre-filled syringe
Primary Outcome Measure Information:
Title
Maximum Concentration（Cmax） of Adalimumab After Single SC Injection of HLX03/Humira
Time Frame
71 days post-dose
Title
Area Under the Plasma Concentration-time Curve From Zero (0) Hours to the last quantifiable concentration
Time Frame
71 days post-dose
Secondary Outcome Measure Information:
Title
Area Under the Plasma Concentration-time Curve From Zero (0) to Time Infinity
Time Frame
71 days post-dose
Title
Time to Maximum Concentration（Tmax） of Adalimumab After Single SC Injection
Time Frame
71 days post-dose
Title
Half-life time of adalimumab after single SC injection of HXL03/Humira
Time Frame
71 days

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy Chinese males (age: 18~45 yrs) with contraception during and 3 months post-dose. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination including blood pressure, pulse, ECG, and laboratory testing. BMI between 19.0 and 28.0 kg/m² and body weight between 55 kg and 80 kg. Exclusion Criteria: suffering from active or latent tuberculosis or history of tuberculosis; have heart disease or a history of heart disease; suffer from mental illness or psychiatric history; suffering from malignant tumors and their history; suffering from herpes zoster and its history; suffering from epilepsy and history of epilepsy; be allergic to the drugs or its components with high sensitivity or allergic reaction, detection of ADA (+); patients who lost blood or donated more than 200 mL within the first 2 months before the screening; major surgery performed within 30 days prior to signing ICF; live vaccine inoculation or vaccination within 12 weeks of screening, or possible administration of vaccine during screening and study visits; previous application of adalimumab or its biosimilars, or anti-TNF alpha drugs; participating in other clinical trials within the first 3 months of the trial; abnormal immune function within 4 weeks before screening; the presence of invasive systemic fungal infection or other opportunistic infections within 2 months prior to screening; systemic or local infection, such as the risk of sepsis and / or known active inflammation within 2 months before screening; 2 months before the screening, there were severe infections in the hospital and / or the need for intravenous antibiotics; 4 or more upper respiratory tract infections occurred within 6 months prior to randomization; hepatitis B surface antigen (HBsAg) positive; if hepatitis B surface antigen (HBsAg) negative, hepatitis B core antibody (HBcAb) positive, peripheral blood hepatitis B virus deoxyribonucleic acid (DNA) test >0 IU/ml also ruled out; hepatitis C virus (HCV) antibody positive; human immunodeficiency virus (HIV) antibody positive; Treponema pallidum (Treponema pallidum, TP) antibody positive; anti nuclear antibody titer was 1:100 examination; drug abusers, alcohol addicts; , the researchers discretion of failure to follow the requirements of the program, instructions and research limitations, such as uncooperative attitude, unable to return to the Research Center for follow-up visits, or unable to complete the entire clinical study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yanhua Ding, MD
Organizational Affiliation
The 1st affiliated hospital, Jilin University, PRC
Official's Role
Principal Investigator
Facility Information:
Facility Name
the 1st affiliated hospital of Jilin University
City
Chang Chun
State/Province
Jilin
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
33682358
Citation
Zhang H, Wu M, Sun J, Zhu X, Li C, Ding Y, Zhang X, Chai K, Li X. Pharmacokinetics, safety, and immunogenicity of HLX03, an adalimumab biosimilar, compared with reference biologic in healthy Chinese male volunteers: Results of a randomized, double-blind, parallel-controlled, phase 1 study. Pharmacol Res Perspect. 2021 Apr;9(2):e00733. doi: 10.1002/prp2.733.
Results Reference
result
Links:
URL
http://dx.doi.org/10.1136/annrheumdis-2019-eular.1909
Description
FRI0086 CHINA-MANUFACTURED ADALIMUMAB BIOSIMILAR, HLX03, DEMONSTRATED PHARMACOKINETIC EQUIVALENCE AND COMPARABLE SAFETY TO REFERENCE ADALIMUMAB，EULAR 2019 (Poster); Annals of the Rheumatic Diseases

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Phase I Study of HLX3 vs Adalimumab in Chinese Healthy Subjects

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