Dataset Information

A Randomized, Double-Blind, Parallel-Group, Phase 1 Clinical Trial Comparing the Pharmacokinetic, Safety, and Immunogenicity of the Biosimilar HS016 and the Originator Adalimumab in Chinese Healthy Male Subjects.

ABSTRACT: A comparison of the immunogenicity, safety, and pharmacokinetic properties of HS016 and its originator, adalimumab, was conducted in Chinese healthy male subjects. This was a phase 1 single-center, randomized, parallel-group double-blind clinical trial. Chinese healthy male subjects (1:1) allocated to HS016 and adalimumab groups were treated with single subcutaneous injections (40 mg/0.8 mL). The pharmacokinetic equivalence of HS016 and adalimumab was assessed by (1) the area under the plasma concentration-time curve (AUC) from time 0 to the last detectable drug concentration (AUC_0-t ), (2) the AUC from time 0 extrapolated to infinity (AUC_0-∞ ), and (3) the maximum plasma concentration (C_max ). Other pharmacokinetic parameters (time to C_max , apparent clearance, and half-life), safety, and immunogenicity were also evaluated. A total of 136 subjects were randomly divided into HS016 (n = 68) or adalimumab (n = 68) groups. The geometric means of AUC_0-t , AUC_0-∞ , and C_max were similar for HS016 and adalimumab. The 90%CIs of AUC_0-t (87.2% to 106.1%), AUC_0-∞ (87.4% to 108.4%), and C_max (98.6% to 113.6%) were all within the prespecified bioequivalence criteria (80% to 125%). The incidence of treatment-emergent adverse events (TEAEs) was similar in both groups, with most TEAEs being mild; only 3 (4.4%) subjects in the HS016 group experienced moderate TEAEs. No significant differences in the time to C_max , apparent clearance, half-life, and immunogenicity were detected. The pharmacokinetic profile of HS016 was equivalent to that of the originator, adalimumab, with similar safety and immunogenicity profiles. HS016 may be considered for assessment in the treatment of patients with ankylosing spondylitis.

SUBMITTER: Cao G

PROVIDER: S-EPMC7984335 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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A Randomized, Double-Blind, Parallel-Group, Phase 1 Clinical Trial Comparing the Pharmacokinetic, Safety, and Immunogenicity of the Biosimilar HS016 and the Originator Adalimumab in Chinese Healthy Male Subjects.

Cao Guoying G Yu Jicheng J Wu Jufang J Wang Jingjing J Xue Yu Y Yang Xiaoli X Zhang Jing J

Clinical pharmacology in drug development 20200528 3

A comparison of the immunogenicity, safety, and pharmacokinetic properties of HS016 and its originator, adalimumab, was conducted in Chinese healthy male subjects. This was a phase 1 single-center, randomized, parallel-group double-blind clinical trial. Chinese healthy male subjects (1:1) allocated to HS016 and adalimumab groups were treated with single subcutaneous injections (40 mg/0.8 mL). The pharmacokinetic equivalence of HS016 and adalimumab was assessed by (1) the area under the plasma co ...[more]

PMID: 32463599

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Project description:IntroductionSB5 is an approved biosimilar of adalimumab, a monoclonal anti-tumor necrosis factor (anti-TNF) antibody. This study compared pharmacokinetics (PK), safety, tolerability, and immunogenicity between a new high-concentration, low-volume, and citrate-free formulation (40 mg/0.4 ml, SB5-HC) and the current low-concentration formulation with higher volume (40 mg/0.8 ml, SB5-LC) to evaluate the bioequivalence of the two formulations.MethodsThis study was a randomized, single-blind, two-arm, parallel-group, single-dose study in healthy male subjects. Subjects were randomized to receive either SB5-HC or SB5-LC via subcutaneous injection using a pre-filled syringe. Primary endpoints were the area under the curve of the concentration-time curve from zero to infinity (AUCinf) and maximum serum concentration (Cmax). Bioequivalence was achieved if the 90% confidence intervals (CIs) for the ratios of the geometric least squares mean (LSMean) of primary endpoints were within the pre-defined bioequivalence margins of 0.80-1.25. Secondary endpoints included safety, tolerability, and immunogenicity.ResultsSubjects (n = 188) were randomized to SB5-HC (n = 94) or SB5-LC (n = 94). Baseline characteristics were comparable between the two treatment groups. The mean values for AUCinf and Cmax were similar between the SB5-HC and SB5-LC groups. For the primary endpoints, the geometric LSMean ratios (90% CI) for AUCinf and Cmax were 0.920 (0.8262-1.0239) and 0.984 (0.9126-1.0604), respectively, placing the corresponding 90% CIs well within the pre-defined bioequivalence margin of 0.80-1.25. All treatment-emergent adverse events (TEAEs) were considered mild to moderate and were reported for 44.7% and 51.1% of subjects in the SB5-HC and SB5-LC groups, respectively. Immunogenicity assessed by frequency of occurrence of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) was comparable between groups.ConclusionsThis bridging study demonstrated PK equivalence and comparable safety and tolerability of subcutaneous injection of SB5 via SB5-HC or SB5-LC.ClinicaltrialsGOV IDENTIFIER: https://clinicaltrials.gov/ct2/show/NCT04514796 .

Project description:BackgroundAVT02 (adalimumab) is a proposed biosimilar to Humira®. AVT02 is produced at a 100 mg/mL concentration with a citrate-free formulation.ObjectivesThe aim of this study was to compare the efficacy, safety and immunogenicity of AVT02 versus Humira® in subjects with moderate to severe chronic plaque psoriasis.MethodsThis double-blind, randomised, parallel group, active control study of adult subjects compared (at a 1:1 ratio) AVT02 with originator adalimumab 80 mg subcutaneously in Week 1, then 40 mg every other week. At Week 16, subjects who had received originator adalimumab were re-randomised at a 1:1 ratio to continue receiving originator adalimumab, or to switch to AVT02, every other week until Week 48, with final efficacy endpoint at Week 50. Subjects who initially received AVT02 continued to receive AVT02 from Week 16 to Week 48. The primary endpoint was percentage improvement in Psoriasis Area and Severity Index (PASI) score at Week 16. Secondary efficacy endpoints included percentage improvement in PASI score at additional timepoints, change from baseline in Dermatology Life Quality Index (DLQI) score and number and percentage of subjects achieving static Physician's Global Assessment (sPGA) responses of 'clear' or 'almost clear'. Additional secondary endpoints included comparison of adverse event profiles, anti-drug antibodies and neutralising antibodies, and serum trough levels of adalimumab at steady state.ResultsA total of 413 subjects were randomised (205 to AVT02 and 208 to originator). The percentage improvement in PASI score at Week 16 was 91.6% for AVT02-treated subjects and 89.6% for originator adalimumab. The 90% confidence intervals for the primary endpoint were within the pre-defined equivalence margin of ±10% (90% CI - 0.76 to 5.29; 95% CI - 1.34 to 5.88), and a comparable pattern for DLQI score (11.4-point and 10.6-point improvement in AVT02-treated and originator adalimumab-treated groups, respectively) and sPGA (90.5% in both groups achieving 'clear' or 'almost clear') at Week 16 supported the assessment. Efficacy persisted through Week 50 of the study in all treatment groups, including those who switched from originator adalimumab to AVT02, for percent improvement in PASI score, quality-of-life assessment and sPGA. The safety, tolerability and immunogenicity profiles between AVT02 and originator adalimumab were similar at Week 16, and this persisted in the switched and continued groups through Week 50.ConclusionObjective and subjective measures of efficacy supported the evaluation of biosimilarity between AVT02 and originator adalimumab at Week 16 and until Week 50, in switched and continued treatment groups. AVT02 was safe and well tolerated, with a safety and immunogenicity profile similar to that observed in originator adalimumab with no clinically meaningful difference between the two.Clinical trial registrationEudraCT: 2017-003367-35; ClinicalTrials.gov: NCT03849404.

Dataset Information

A Randomized, Double-Blind, Parallel-Group, Phase 1 Clinical Trial Comparing the Pharmacokinetic, Safety, and Immunogenicity of the Biosimilar HS016 and the Originator Adalimumab in Chinese Healthy Male Subjects.

Publications

A Randomized, Double-Blind, Parallel-Group, Phase 1 Clinical Trial Comparing the Pharmacokinetic, Safety, and Immunogenicity of the Biosimilar HS016 and the Originator Adalimumab in Chinese Healthy Male Subjects.

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