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A Phase I, Randomized, Single-Blind, Single-Dose Study to Compare Pharmacokinetic Characteristics and Safety of FKB327 with those of Humira in Healthy Adult Male Subjects (FKB327-004 Study)

Bioequivalence study of FKB327 and adalimumab in healthy adult male subjects (FKB327-004 Study)

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In total, 131 Japanese healthy adult male subjects were randomized: 66 subjects in FKB327 treatment group and 65 subjects in Humira treatment group, respectively. One subject in the FKB327 treatment group withdrew himself from the study before the study drug administration. All subjects who received the study drug completed the study. Pharmacokinetics: A total of 130 subjects (65 subjects each in FKB327 treatment group and in Humira treatment group) who received the study drug were analyzed as PK Analysis Set. Mean age (SD) in FKB327 treatment group and Humira treatment group was 28.1 (6.96) years and 28.2 (8.12) years, mean BMI (SD) at baseline was 21.14 (1.581) kg/m2 and 21.15 (1.549) kg/m2, mean body weight (SD) at baseline was 61.92 (6.175) kg and 62.56 (6.412) kg, respectively.

Total of 130 subjects who consented to perticipate the study was randomly assigned to recieve either FKB327 or Humira treatment groups subcutaneously at abdomen. (1) Treatment groups: Test drug (FKB327): Reference drug (Humira) = 1:1 (2) Stratification factor: weight classification (stratified less than 65 kg, greater than or equal to 65 kg)

Proportions of subjects experienced at least 1 Treatment-emergent adverse event (TEAE) was total of 54 (41.5%) subjects (25 (38.5%) in FKB327, 29 (44.6%) in Humira). Of these, 51 (39.2%) subjects (23 (35.4%) in FKB327, 28 (43.1%) in Humira) experienced related AE. No subjects experienced serious AE (SAE) and TEAEs. There was no death during the study. The most commonly reported TEAEs (number of subjects, percentage in total) were nasopharyngitis (FKB327: 9 (13.8%), Humira: 8 (12.3%)), injection site reaction (FKB327: 3 (4.6%), Humira: 9 (13.8%)), and headache (FKB327: 7 (10.8%), Humira: 4 (6.2%)). In laboratory testing, none was considered clinically significant laboratory abnormal changes and changes were similar in both treatment groups.There were no clinically significant ECG abnormalities. Immugenicity, there was no significant evidence for a difference in the prevalence of anti-drug antibody (ADA) and neutralizing anti-body (NAB) activities between the treatments. The distribution of ADA titer categories was comparable between the treatments. Tolerability at the injection site was good for both treatment groups. Median VAS score (range) immeadiatly after injection of study drug was 2.0 (0 - 30) in FKB327 and 22.0 (0 - 87) in Hmuira.

Tmax (median) was observed at 168 hours and 144 hours postdose following single sc administration of FKB327 or Humira, respectively, same hereinafter. Thereafter, serum concentrations declined and their T1/2 (geometric mean) were 330 and 289 hours. Although mean serum adalimumab concentration-time profiles were very similar, mean serum adalimumab concentration was slightly higher throughout for FKB327 than for Humira. The primary PK similarity analysis based on ANOVA approach (no adjustment by protein content of drugs) showed that, the 90% confidence interval (CI) of the geometric least squares (LS) mean ratios for Cmax and AUC0-360h were fully contained within the pre-defined PK similarity range of 0.80 to 1.25, although the upper limit of 90% CI of the geometric LS mean ratio for AUC0-t was slightly outside the pre-defined range. The pre-specified supplementary analysis of the primary analysis based on the ANCOVA using ADA categorical titers as a covariate showed that the 90% CIs of the geometric LS mean ratios for all of primary PK parameters were fully contained within the pre-defined PK similarity range of 0.80 to 1.25.

In the primary PK similarity analysis, the 90% CIs of the geometric LS mean ratios for Cmax and AUC0-360h were fully contained within the predefined PK similarity range of 0.80 to 1.25, although the upper limit of 90% CI of the geometric LS mean ratio for AUC0-t was slightly outside the pre-defined range. In the planned supplementary analysis including the ADA categorical titers as a covariate, all primary PK endopoint met equivalent range.

Dec. 31, 2020

https://jrct.mhlw.go.jp/latest-detail/jRCT2071200058

Yonemura Takuma

SOUSEIKAI Sumida Hospital

1-29-1 Honjo, Sumida-ku, Tokyo

fkb-clinical@fk-b.com

Arai Yasumasa

Fujifilm Kyowakirin Biologics Co. Ltd.

1-6-1 Ohtemachi, Chiyoda-ku, Tokyo

+81-3-3282-0700

yasumasa.arai@fk-b.com

Complete

Dec. 21, 2015

Interventional

randomized controlled trial

single blind

active control

parallel assignment

treatment purpose

Japanese healthy male subjects
aged 20 to 44 years, with body mass index (BMI) of >= 18.5 and < 25.0 kg/m2.

1. History or presence of illness (including drug or alcohol dependence, drug allergy, allergic disease (including severe natural rubber-latex allergy), respiratory disease, endocrine, renal, or hepatic disease, diabetes mellitus, or cardiac disease)
2. A history of cancer.
3. History or presence of psychiatric disease.
4. Evidence of any significant bacterial, viral, fungal, or parasitic infection within 28 days before dosing.
5. Positive for any one of infectious disease testing (Hepatitis B surface (HBs), anti-HBc antibody, Hepatitis C virus (HCV), Human immunodeficiency virus (HIV) antigen-antibody), and tuberculosis.
6. Positive for any one of drugs of abuse test.
7. History of hepatitis B.
8. Participated in another clinical study or any other type of medical research within 4 months before dosing.
9. Previous treatment with adalimumab.
10. Receipt of a live vaccine (e.g., BCG, polio, measles, rubella) within the 3 months before dosing.
11. History of ADAs to any drug.

Male

Rheumatoid arthritis

Experimental: FKB327 (Adalimumab biosimilar)
Intervention Description: Single-dose 40 mg of FKB327 administered subcutaneously injection on day 1.
Drug: FKB327 provided as a prefilled syringe contain 40 mg / 0.8 mL of drug

Active Comparator: US licenced Adalimumab
Single-dose 40 mg administered of US licenced Adalimumab subcutaneously injection on day 1.
Drug: US licenced Adalimumab provided as a prefilled syringe contain 40 mg / 0.8 mL of drug

D001172

Pharmacokinetics parameters for bioequivalence: Cmax, AUC0-360, AUC0-t

Secondary pharmacokinetics parameters: AUC0-infinity, Tmax, T1/2
Safety evaluation: Adverse event, Laboratory tests, 12-lead electrocardiogram (ECG), anti-drug antibody (ADA), Local tolerability (injection site reaction, Visual Analogue Scale (VAS) for pain at the injection site)

+81-92-283-7701

Dec. 18, 2015

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