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A Phase I, Randomized, Single-Blind, Multicenter, Parallel-Group, Single-Dose Study to Compare Pharmacokinetic Characteristics and Safety of FKB327 with those of Humira in Healthy Adult Male Subjects (FKB327-006 Study)

Bioequivalence study of FKB327 and adalimumab in healthy adult male subjects; Multicenter study (FKB327-006 Study)

130

In total, 134 Japanese healthy adult male subjects were randomized: 66 subjects in FKB327 treatment group and 68 subjects in Humira treatment group, respectively. Of these, 4 subjects were randomized but later discontinued from the study before study drug administration (One subject each in FKB327 and Humira withdrew the consent by himself, and 2 subjects in Humira were discontinued from the study due to an adverse event). All subjects who received the study drug completed the study. Total of 130 subjects (65 subjects in FKB327 and 65 subjects in Humira) who received the study drugs were analized as PK Analysis Set. Mean age in FKB327 treatment group and Humira treatment group was 26.5 (range 20 to 44 years) years and 27.1 (range 20 to 44 years) years, mean BMI (SD) at baseline was 21.23 (1.905) kg/m2 and 21.20 (1.695) kg/m2, mean body weight (SD) at baseline was 61.74 (7.087) kg and 62.09 (6.269) 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 thigh. (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 51 (39.2%) subjects (20 (30.8%) in FKB327, 31 (47.7%) in Humira). Of these, 43 (33.1%) subjects (17 (26.2%) in FKB327, 26 (40.0%) in Humira) experienced related AE. No subjects experienced serious AE (SAE) and TEAEs. There was no death during the study. The most common TEAEs (number of subjects, percentage in total) were injection site reaction in 9 subjects (13.8%), 13 subjects (20.0%) and nasopharyngitis in 3 subjects(4.6%), 8 subjects (12.3%), respectively. 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 192 hours post-dose following single sc administration (thigh) of both FKB327 and Humira. Thereafter, serum concentrations declined and their T1/2 (geometric mean) were 281 hours (approximately 11.7 days) and 275 hours (approximately 11.5 days) for FKB327 and Humira, respectively. Although mean serum adalimumab concentration-time profiles were very similar, mean serum adalimumab concentration was slightly higher throughout for FKB327 than for Humira. Primary PK analysis were performed by ANCOVA including covariates (trial site, body weight, age) and using the corrected serum drug concentration, which was calculated by multiplying the ratio of protein content from both drug products of FKB327 and Humira used in this study. As a secondary PK analusis, ANOVA and ANCOVA with the same covariates were performed using the measured serum drug concentration (no correction by protein contain of drugs). In primary PK analysis, the 90% confidence interval (CI) of the geometric least squares (LS) mean ratios of primary PK parameters (Cmax and AUC0-t) and secondary PK parameters (AUC0-infinity, AUC0-360h, and t1/2) were fully contained within the pre-defined PK similarity range of 0.80 to 1.25. Additionally, a similar trend was observed in the results of both ANOVA and ANCOVA using measured serum drug concentration, in which the geometric LS mean ratios with the 90% CIs for primary PK parameters (Cmax and AUC0-t) were 1.05 (1.00, 1.11) and 1.11 (1.01, 1.23) by ANOVA, 1.05 (1.01, 1.10) and 1.12 (1.01, 1.23) by ANCOVA, respectively.

The primary PK similarity analysis showed that, in the primary PK parameters (Cmax and AUC0-t) and secondary PK parameters (AUC0-infinity, AUC0-360h, and t1/2), the 90% CIs of the geometric LS mean ratios were fully contained within the pre-defined PK similarity range of 0.80 to 1.25. There was no difference in safety profile and immunogenicity between the treatment groups. The study demonstrated PK similarity and confirmed comparable safety profiles between FKB327 and Humira.

Dec. 31, 2020

https://jrct.mhlw.go.jp/latest-detail/jRCT2071200057

Yazawa Rie

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

July. 08, 2017

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-t

Secondary pharmacokinetics parameters: AUC0-infinity, Tmax, T1/2
Safety: Adverse events, Laboratory tests, Vital signs, 12-lead ECG, Anti-drug antibody, Local tolerability, Injection site reaction

+81-92-283-7701

June. 16, 2017

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