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A Randomised, Double Blind, Two-Arm, Single Dose, Parallel Phase I Study To Compare the Pharmacokinetics, Safety and Immunogenicity of MB02 (a proposed bevacizumab biosimilar drug) and EU-approved Avastin in Japanese Healthy Male Volunteers

A Randomised, Double Blind, Two-Arm, Single Dose, Parallel Phase I Study To Compare the Pharmacokinetics, Safety and Immunogenicity of MB02 (a proposed bevacizumab biosimilar drug) and EU-approved Avastin in Japanese Healthy Male Volunteers

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The mean age was 28.3 years and 28.5 years and the mean BMI was 22.54 kg/m2 and 23.33 kg/m2 for MB02 and EU Avastin treatment arms, respectively.

Number of subjects by treatment arm: 24 Number of subjects who completed the study: 48

Overall, the administration of MB02 and EU Avastin, was safe and well tolerated in healthy Japanese male subjects following a single IV infusion dose of 3 mg/kg. A total of 47 TEAEs were reported by 20 (41.7 %) of the 48 subjects who received study medication and had at least 1 post-dose safety assessment (safety population).Overall, subjects who received MB02 reported TEAEs at an incidence slightly lower (8 subjects; 33.3 %) than subjects who received EU Avastin (12 subjects; 50.0 %). The number of TEAEs reported was comparable in subjects who received MB02 (22 TEAEs) and subjects who received EU Avastin (25 TEAEs), and none of these TEAEs was rated as grade >= 3 in severity. No relevant differences were observed between the treatment arms with respect to mean values and changes from baseline for clinical laboratory results, vital signs, and ECG results.

Overall, the statistical analysis confirmed that MB02 (test) was similar to EU Avastin (reference). The ratio of geometric least squares (LS) means for AUC(0-inf.) was 1.04. The 90% CI for the geometric means ratio for the primary PK endpoint of AUC(0-inf. (0.981, 1.11) was fully contained within the predefined equivalence limits of 0.80 to 1.25.

The majority of subjects tested negative for ADA at all-time points. The development of ADA and nAb were considered to have no appreciable effect on clearance and were not associated with any safety signal.

Results from the primary PK endpoint analysis (AUC(0-inf.)) demonstrated equivalence between MB02 and the reference EU Avastin following a single 3 mg/kg dose administered as a 90 minute IV infusion in healthy Japanese male subjects. The safety results of this single dose study demonstrate that the safety profile of the test product MB02 is similar to that of the reference product, EU Avastin in a population of healthy Japanese subjects.

No

Syneos Health Clinical K.K.

2-1-3 Nihonbashi, Chuo-ku, Tokyo 103-0027 JAPAN

Hiroaki.Kitajima@inventivhealth.com

Syneos Health Clinical K.K.

2-1-3 Nihonbashi, Chuo-ku, Tokyo 103-0027 JAPAN

Hiroaki.Kitajima@inventivhealth.com

completed

Sept. 19, 2019

Interventional

Randomized (1:1), double blind, single-dose, two arms, parallel phase 1 study

treatment purpose

1

1) Subjects with Body mass index (BMI) between =>18.5 to =<28 kg/m2 and total body weight between =>50 and =<100 kg, at Screening
2) Systolic blood pressure =<140 mm Hg and diastolic blood pressure =<90 mm H g.
3) Computerized (12-lead) ECG recording without signs of clinically relevant pathology.
4) All other values for hematology, coagulation and for biochemistry and urinalysis tests of blood and urine within the normal range or showing no clinically relevant deviations as judged by the Investigator, according to the laboratory values from study value.
5) Ability and willingness of accordance with limitation rules in the study period.

History of bleeding disorders or protein C, protein S, and/or factor V Leiden deficiency
2) Known history of clinically significant essential hypertension (subjects under any
antihypertensive treatment included), orthostatic hypotension, fainting spells or
blackouts for any reason, cardiac failure or history of thromboembolic conditions
3) History of GI perforation, ulcers, gastro-oesophageal reflux, inflammatory bowel
disease, diverticular disease, diverticular disease, any fistulae, pulmonary hemorrhage
(hemoptysis) or reversible posterior leukoencephalopathy syndrome
4) Significant history or clinical manifestation of any metabolic, allergic, dermatological,
hepatic, renal, haematological, pulmonary, cardiovascular, gastrointestinal,
neurological, respiratory, endocrine, or psychiatric disorder, as determined by the
Investigator (or designee)
5) Any current or recent history of active infections, including localized infections.

Male

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investigational material(s)
Generic name etc : MB02
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : 3 mg/kg, administered as a 90 minute IV infusion

control material(s)
Generic name etc : Bevacizuma
INN of investigational material : Bevacizuma
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : 3 mg/kg, administered as a 90 minute IV infusion

bioequivalence
To demonstrate pharmacokinetic similarity, as primary assessed by the Area Under the Concentration-time curve extrapolated to infinity (AUC(0-inf)) between the two study arms, MB02 and EU-Avastin

safety
pharmacokinetics
other
- Evaluation and comparison of derived PK parameters not covered by the primary endpoints for MB02 and EU approved Avastin
- To compare the safety profile of MB02 and EU approved Avastin
- To compare the immunogenicity of MB02 and EU approved Avastin

+81-92(283)7701

Aug. 02, 2019