Healthy Volunteers
Conditions
Brief summary
Randomized, double blind, parallel group, single dose, 3 arm study to investigate and compare the PK, safety and immunogenicity profile of MB02-DM with MB02-SP and US-Avastin® in healthy male subjects. During the course of the study, the similarity in pharmacokinetics will be assessed by sampling the levels of drug in the blood, and by comparing these levels among the different administration arms. Safety, tolerability, and immunologic response to the administered drugs will also be evaluated throughout.
Detailed description
The primary PK parameter endpoints are Cmax and AUC0-∞ for bevacizumab. The secondary PK endpoints will include all other PK parameters for bevacizumab, including tmax, t1/2, CL and AUC(0-t). The serum PK parameters of bevacizumab will be calculated using standard noncompartmental methods. An analysis of covariance model will be used to analyse the log-transformed primary PK parameters (AUC\[0 ∞\] and Cmax) and AUC(0-t). The model will include a fixed effect for treatment and body weight as a covariate. All other PK parameters will not be subject to inferential statistical analysis. Estimates of geometric mean ratios together with the corresponding 90% confidence intervals (CI) will be derived for the comparisons of the PK parameters as follows: * MB02-SP versus MB02-DM * MB02-SP versus US Avastin® * MB02-DM versus US Avastin® PK similarity will be achieved if the 90% CIs for the biosimilar-to-reference ratios of PK endpoints (AUC\[0-∞\] and Cmax) fall within the predefined 0.80-1.25 acceptance similarity criteria for all 3 pairwise comparisons; MB02-SP versus MB02-DM; MB02-SP versus US Avastin®; and MB02-DM versus US Avastin®. All AEs will be listed and summarised using descriptive methodology. All observed or patient-reported AEs will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The incidence of AEs for each treatment will be presented by severity and by association with the study drugs as determined by the Investigator (or designee). Each AE will be coded using the Medical Dictionary for Regulatory Activities. All safety data will be listed and summarised as appropriate. Immunogenicity data (overall ADA incidence and titters, and neutralising ADA results) will be listed. A summary of the number and percent of subjects testing positive for ADA or neutralising antibodies before the dose of MB02-SP, MB02-DM, or US Avastin® (Day -1) and at scheduled post dose assessments will be presented by treatment arm. All safety data and immunogenicity data summaries will be based on the safety analysis population. Select analyses may be repeated for subsets with or without ADA and de novo ADA formation as appropriate.
Interventions
DRUGMB02-SP
Solution for intravenous infusion, single dose of 1mg/kg, administered as 90-minute infusion
DRUGMB02-DM
Solution for intravenous infusion, single dose of 1mg/kg, administered as 90-minute infusion
Solution for intravenous infusion, single dose of 1mg/kg, administered as 90-minute infusion
Sponsors
mAbxience Research S.L.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Males of any race, between 18 and 55 years of age, inclusive, at Screening. 2. Body mass index between 18.5 and 29.9 kg/m2, inclusive, at Screening. 3. Total body weight between 50 and 95 kg, inclusive, at Screening. 4. In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital sign measurements, and clinical laboratory evaluations (congenital non-haemolytic hyperbilirubinemia \[eg, Gilbert's syndrome\] is acceptable) at Screening or Check-in as assessed by the Investigator (or designee). 5. Relevant clinical laboratory evaluations of haematology, coagulation, urinalysis and clinical chemistry within normal range at Screening and Check in as follows. A single repeat test will be allowed at each timepoint. * Absolute neutrophil count ≥1.5 × 109 L * Platelet count ≥100 × 109 L * Haemoglobin \>10 g/dl * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5 x ULN * Alkaline phosphatase (ALP) ≤1.5 × ULN * Total bilirubin \<1.5 × ULN (\<51.30 µmol/L in subjects with Gilbert's syndrome) * Blood urea nitrogen ≤1.5 × ULN * Creatinine \<132.63 µmol/L * Serum albumin: \>35 g/L * Low density lipoprotein cholesterol ≤ 4.9 mmol/L * High density lipoprotein cholesterol ≥ 0.85 mmol/L * Creatine kinase (CK) \<2 × ULN * International normalised ratio (INR) 0.8 to 1.3 * Urine dipstick for proteinuria \<2+ 6. Systolic blood pressure ≥90 mmHg and \<140 mmHg and diastolic blood pressure ≥50 mmHg and \<90 mmHg at Screening and Check in. 7. Subjects agree to use contraception. 8. Able to comprehend and willing to sign an informed consent form (ICF) and to abide by the study restrictions. Subjects must have signed an informed consent before any study-related procedure or evaluation is performed.
Exclusion criteria
1. 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). 2. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee). 3. Any current or recent history of active infections, including localised infections (Within 2 months prior Screening Visit for any serious infection which requires hospitalization or intravenous anti-infective, and within 14 days prior Screening Visit for any active infection which requires oral treatment). 4. History of, or planned surgery, including suturing, dental surgery or wound dehiscence within 30 days of dosing, or within 30 days of the last study visit. 5. Presence of a nonhealing wound or fracture. 6. Known history of clinically significant essential hypertension, orthostatic hypotension, fainting spells or blackouts for any reason, cardiac failure or history of thromboembolic conditions. 7. Medically significant dental disease or dental neglect, with signs and/or symptoms of local or systemic infection that would likely require a dental procedure during the course of the study. 8. Clinically relevant history of alcoholism, addiction or drug/chemical abuse prior to Check-in, and/or positive alcohol breath test and/or urinary drug test screen (confirmed by repeat) at Screening or Check in. 9. History of bleeding disorders or protein C, protein S, and/or factor V Leiden deficiency. 10. History of clinically significant haemorrhage, epistaxis, GI bleeding, haemorrhoids and/or haemoptysis. 11. History of GI perforation, ulcers, gastro oesophageal reflux, inflammatory bowel disease, diverticular disease, or any fistulae. 12. Alcohol consumption of \>24 units per week. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits. 13. Positive hepatitis panel, positive human immunodeficiency test. Subjects whose results are compatible with prior immunisation and not infection may be included at the discretion of the Investigator. 14. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days prior to Check-in, or within 5 half lives of the investigational drug used in the study. 15. Use or intend to use slow-release medications/products considered to still be active within 30 days prior to Check-in, unless deemed acceptable by the Investigator (or designee). 16. Use or intend use of any prescription medications/ nonprescription products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to Check-in, unless deemed acceptable by the Investigator or designee. 17. Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant derived preparations within 7 days prior to Check-in, unless deemed acceptable by the Investigator (or designee). 18. Have received a live or attenuated vaccine from 3 months prior to Screening or have the intention to receive a vaccine during the study. 19. Intend to travel to a region where a vaccination will be required due to endemic disease within 3 months of dosing. 20. Previous treatment with an anti VEGF antibody or any other protein or antibody targeting the VEGF receptor. 21. Use of tobacco- or nicotine-containing products within 1 year prior to Check-in, or positive cotinine test upon Screening or Check-in. 22. Receipt of blood products within 60 days prior to Check-in. 23. Donation of blood from 90 days prior to Screening, plasma from 14 days prior to Screening, or platelets from 42 days prior to Screening. 24. Poor peripheral venous access. 25. History of abnormal peripheral sensation including paraesthesia and/or numbness in arms and/or legs. 26. Have previously completed or withdrawn from this study or any other study investigating bevacizumab, and/or have previously received bevacizumab. 27. Subjects who, in the opinion of the Investigator (or designee), should not participate in this study. 28. Vulnerable subjects (e.g. persons kept in detention). 29. Subjects who are study site employees or immediate family members of a study site or Mabxience employee.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) - (AUC[0-∞]) | Pre-dose (0 hours),end of infusion, 2, 3, 4, 5, 6, 7, 12, and 24 hours and at Days 3, 4, 5, 6, 7, 8, 10, 14, 21, 28, 42, 56, 78, and 100 post-dose | Compare the pharmacokinetic (PK) profiles of the 3 arms (AUC\[0-∞\]) |
| Pharmacokinetics (PK) - (Cmax) | Pre-dose (0 hours),end of infusion, 2, 3, 4, 5, 6, 7, 12, and 24 hours and at Days 3, 4, 5, 6, 7, 8, 10, 14, 21, 28, 42, 56, 78, and 100 post-dose | Compare the pharmacokinetic (PK) profiles of the 3 arms (Cmax) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Other PK Parameters (CL) | Pre-dose (0 hours),end of infusion, 2, 3, 4, 5, 6, 7, 12, and 24 hours and at Days 3, 4, 5, 6, 7, 8, 10, 14, 21, 28, 42, 56, 78, and 100 post-dose | Evaluation of all other PK parameters (CL) CL = total body clearance of drug after intravenous administration |
| Other PK Parameters (t1/2) | Pre-dose (0 hours),end of infusion, 2, 3, 4, 5, 6, 7, 12, and 24 hours and at Days 3, 4, 5, 6, 7, 8, 10, 14, 21, 28, 42, 56, 78, and 100 post-dose | Evaluation of all other PK parameters (t1/2) t½ = apparent serum terminal elimination half-life |
| Other PK Parameters (Tmax) | Pre-dose (0 hours),end of infusion, 2, 3, 4, 5, 6, 7, 12, and 24 hours and at Days 3, 4, 5, 6, 7, 8, 10, 14, 21, 28, 42, 56, 78, and 100 post-dose | Evaluation of all other PK parameters (tmax) tmax = time of maximum observed serum concentration |
| Safety (Number of Participants Reporting Treatment-related Adverse Events) | Day 1 - Day 100 | Number of participants who reported Treatment-related Adverse Events using the CTCAE v5.0 criteria |
| Safety (Treatment-related Adverse Events) | Day 1 - Day 100 | Treatment-related Adverse Events based on the CTCAE v5.0 criteria reported by the study participants |
| Immunogenicity | Days -1, 14, 28, 56 and 78 | Number of participants with anti-bevacizumab antiboides (ADA), including neutralizing antibodies (Nab). Subjects who tested positive at baseline are not included here. |
| Other PK Parameters (AUC[0 t]) | Pre-dose (0 hours),end of infusion, 2, 3, 4, 5, 6, 7, 12, and 24 hours and at Days 3, 4, 5, 6, 7, 8, 10, 14, 21, 28, 42, 56, 78, and 100 post-dose | Evaluation of all other PK parameters (AUC\[0 t\]) AUC(0-t) = AUC from time zero to the time of last quantifiable concentration |
Countries
New Zealand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MB02-SP (Bevacizumab Biosimilar) Sterile vial 100mg/4ml, single-dose 1mg/kg administered as 90-minute infusion on day 1.
MB02-SP: Solution for intravenous infusion, single dose of 1mg/kg, administered as 90-minute infusion | 37 |
| MB02-DM (Bevacizumab Biosimilar) Sterile vial 100mg/4ml, single-dose 1mg/kg administered as 90-minute infusion on day 1.
MB02-DM: Solution for intravenous infusion, single dose of 1mg/kg, administered as 90-minute infusion | 39 |
| US Licenced Avastin® Sterile vial 100mg/4ml, single-dose 1mg/kg administered as 90-minute infusion on day 1.
US licenced Avastin®: Solution for intravenous infusion, single dose of 1mg/kg, administered as 90-minute infusion | 38 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | MB02-SP (Bevacizumab Biosimilar) | MB02-DM (Bevacizumab Biosimilar) | US Licenced Avastin® | Total |
|---|---|---|---|---|
| Age, Continuous | 31.2 years STANDARD_DEVIATION 11.15 | 30.8 years STANDARD_DEVIATION 10.44 | 34.1 years STANDARD_DEVIATION 10.68 | 32.04 years STANDARD_DEVIATION 10.76 |
| BMI | 24.94 kg/m^2 STANDARD_DEVIATION 2.396 | 24.34 kg/m^2 STANDARD_DEVIATION 2.162 | 24.79 kg/m^2 STANDARD_DEVIATION 2.786 | 24.68 kg/m^2 STANDARD_DEVIATION 2.47 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 5 Participants | 4 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 6 Participants | 5 Participants | 18 Participants |
| Race (NIH/OMB) White | 23 Participants | 27 Participants | 27 Participants | 77 Participants |
| Sex/Gender, Customized Only male subjects | 37 Participants | 39 Participants | 38 Participants | 114 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 37 | 0 / 39 | 0 / 38 |
| other Total, other adverse events | 14 / 37 | 22 / 39 | 24 / 38 |
| serious Total, serious adverse events | 0 / 37 | 0 / 39 | 0 / 38 |
Outcome results
Primary
Pharmacokinetics (PK) - (AUC[0-∞])
Compare the pharmacokinetic (PK) profiles of the 3 arms (AUC\[0-∞\])
Time frame: Pre-dose (0 hours),end of infusion, 2, 3, 4, 5, 6, 7, 12, and 24 hours and at Days 3, 4, 5, 6, 7, 8, 10, 14, 21, 28, 42, 56, 78, and 100 post-dose
Population: The PK population included all subjects who received the full dose of MB02-SP, MB02-DM or US-Avastin®, did not had any major protocol deviations, and had evaluable PK data for at least one timepoint
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MB02-SP (Bevacizumab Biosimilar) | Pharmacokinetics (PK) - (AUC[0-∞]) | 7500000 h*ng/ml | Geometric Coefficient of Variation 12.3 |
| MB02-DM (Bevacizumab Biosimilar) | Pharmacokinetics (PK) - (AUC[0-∞]) | 8000000 h*ng/ml | Geometric Coefficient of Variation 15.8 |
| US Licenced Avastin® | Pharmacokinetics (PK) - (AUC[0-∞]) | 7520000 h*ng/ml | Geometric Coefficient of Variation 14.4 |
90% CI: [0.899, 0.989]
90% CI: [0.956, 1.05]
90% CI: [1.01, 1.12]
Primary
Pharmacokinetics (PK) - (Cmax)
Compare the pharmacokinetic (PK) profiles of the 3 arms (Cmax)
Time frame: Pre-dose (0 hours),end of infusion, 2, 3, 4, 5, 6, 7, 12, and 24 hours and at Days 3, 4, 5, 6, 7, 8, 10, 14, 21, 28, 42, 56, 78, and 100 post-dose
Population: The PK population included all subjects who received the full dose of MB02-SP, MB02-DM or US-Avastin®, did not had any major protocol deviations, and had evaluable PK data for at least one timepoint
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MB02-SP (Bevacizumab Biosimilar) | Pharmacokinetics (PK) - (Cmax) | 25600 ng/ml | Geometric Coefficient of Variation 15.7 |
| MB02-DM (Bevacizumab Biosimilar) | Pharmacokinetics (PK) - (Cmax) | 27400 ng/ml | Geometric Coefficient of Variation 14.9 |
| US Licenced Avastin® | Pharmacokinetics (PK) - (Cmax) | 26100 ng/ml | Geometric Coefficient of Variation 16.6 |
90% CI: [0.887, 0.989]
90% CI: [0.925, 1.05]
90% CI: [0.991, 1.11]
Secondary
Immunogenicity
Number of participants with anti-bevacizumab antiboides (ADA), including neutralizing antibodies (Nab). Subjects who tested positive at baseline are not included here.
Time frame: Days -1, 14, 28, 56 and 78
Population: The safety population included all subjects exposed to MB02-SP, MB02-DM or US-Avastin®, and had at least one post dose safety assessment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MB02-SP (Bevacizumab Biosimilar) | Immunogenicity | nAb positive | 0 participants |
| MB02-SP (Bevacizumab Biosimilar) | Immunogenicity | ADA positive | 8 participants |
| MB02-DM (Bevacizumab Biosimilar) | Immunogenicity | nAb positive | 0 participants |
| MB02-DM (Bevacizumab Biosimilar) | Immunogenicity | ADA positive | 13 participants |
| US Licenced Avastin® | Immunogenicity | ADA positive | 9 participants |
| US Licenced Avastin® | Immunogenicity | nAb positive | 0 participants |
Secondary
Other PK Parameters (AUC[0 t])
Evaluation of all other PK parameters (AUC\[0 t\]) AUC(0-t) = AUC from time zero to the time of last quantifiable concentration
Time frame: Pre-dose (0 hours),end of infusion, 2, 3, 4, 5, 6, 7, 12, and 24 hours and at Days 3, 4, 5, 6, 7, 8, 10, 14, 21, 28, 42, 56, 78, and 100 post-dose
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MB02-SP (Bevacizumab Biosimilar) | Other PK Parameters (AUC[0 t]) | 7010000 h*ng/ml | Geometric Coefficient of Variation 14.8 |
| MB02-DM (Bevacizumab Biosimilar) | Other PK Parameters (AUC[0 t]) | 7550000 h*ng/ml | Geometric Coefficient of Variation 16.9 |
| US Licenced Avastin® | Other PK Parameters (AUC[0 t]) | 7110000 h*ng/ml | Geometric Coefficient of Variation 15.4 |
Secondary
Other PK Parameters (CL)
Evaluation of all other PK parameters (CL) CL = total body clearance of drug after intravenous administration
Time frame: Pre-dose (0 hours),end of infusion, 2, 3, 4, 5, 6, 7, 12, and 24 hours and at Days 3, 4, 5, 6, 7, 8, 10, 14, 21, 28, 42, 56, 78, and 100 post-dose
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MB02-SP (Bevacizumab Biosimilar) | Other PK Parameters (CL) | 0.0103 L/h | Geometric Coefficient of Variation 13.9 |
| MB02-DM (Bevacizumab Biosimilar) | Other PK Parameters (CL) | 0.00975 L/h | Geometric Coefficient of Variation 15.2 |
| US Licenced Avastin® | Other PK Parameters (CL) | 0.0104 L/h | Geometric Coefficient of Variation 16.5 |
Secondary
Other PK Parameters (t1/2)
Evaluation of all other PK parameters (t1/2) t½ = apparent serum terminal elimination half-life
Time frame: Pre-dose (0 hours),end of infusion, 2, 3, 4, 5, 6, 7, 12, and 24 hours and at Days 3, 4, 5, 6, 7, 8, 10, 14, 21, 28, 42, 56, 78, and 100 post-dose
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MB02-SP (Bevacizumab Biosimilar) | Other PK Parameters (t1/2) | 390 hours | Geometric Coefficient of Variation 17.2 |
| MB02-DM (Bevacizumab Biosimilar) | Other PK Parameters (t1/2) | 393 hours | Geometric Coefficient of Variation 11.1 |
| US Licenced Avastin® | Other PK Parameters (t1/2) | 396 hours | Geometric Coefficient of Variation 14.4 |
Secondary
Other PK Parameters (Tmax)
Evaluation of all other PK parameters (tmax) tmax = time of maximum observed serum concentration
Time frame: Pre-dose (0 hours),end of infusion, 2, 3, 4, 5, 6, 7, 12, and 24 hours and at Days 3, 4, 5, 6, 7, 8, 10, 14, 21, 28, 42, 56, 78, and 100 post-dose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MB02-SP (Bevacizumab Biosimilar) | Other PK Parameters (Tmax) | 4.02 hours |
| MB02-DM (Bevacizumab Biosimilar) | Other PK Parameters (Tmax) | 5.00 hours |
| US Licenced Avastin® | Other PK Parameters (Tmax) | 5.00 hours |
Secondary
Safety (Number of Participants Reporting Treatment-related Adverse Events)
Number of participants who reported Treatment-related Adverse Events using the CTCAE v5.0 criteria
Time frame: Day 1 - Day 100
Population: The safety population included all subjects exposed to MB02-SP, MB02-DM or US-Avastin®, and had at least one post dose safety assessment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MB02-SP (Bevacizumab Biosimilar) | Safety (Number of Participants Reporting Treatment-related Adverse Events) | Subjects with TEAEs | 24 Participants |
| MB02-SP (Bevacizumab Biosimilar) | Safety (Number of Participants Reporting Treatment-related Adverse Events) | Subjects with SAEs | 0 Participants |
| MB02-SP (Bevacizumab Biosimilar) | Safety (Number of Participants Reporting Treatment-related Adverse Events) | Subjects discontinued due to TEAEs | 0 Participants |
| MB02-SP (Bevacizumab Biosimilar) | Safety (Number of Participants Reporting Treatment-related Adverse Events) | Deaths | 0 Participants |
| MB02-DM (Bevacizumab Biosimilar) | Safety (Number of Participants Reporting Treatment-related Adverse Events) | Deaths | 0 Participants |
| MB02-DM (Bevacizumab Biosimilar) | Safety (Number of Participants Reporting Treatment-related Adverse Events) | Subjects with TEAEs | 23 Participants |
| MB02-DM (Bevacizumab Biosimilar) | Safety (Number of Participants Reporting Treatment-related Adverse Events) | Subjects discontinued due to TEAEs | 0 Participants |
| MB02-DM (Bevacizumab Biosimilar) | Safety (Number of Participants Reporting Treatment-related Adverse Events) | Subjects with SAEs | 0 Participants |
| US Licenced Avastin® | Safety (Number of Participants Reporting Treatment-related Adverse Events) | Deaths | 0 Participants |
| US Licenced Avastin® | Safety (Number of Participants Reporting Treatment-related Adverse Events) | Subjects with SAEs | 0 Participants |
| US Licenced Avastin® | Safety (Number of Participants Reporting Treatment-related Adverse Events) | Subjects discontinued due to TEAEs | 0 Participants |
| US Licenced Avastin® | Safety (Number of Participants Reporting Treatment-related Adverse Events) | Subjects with TEAEs | 29 Participants |
Secondary
Safety (Treatment-related Adverse Events)
Treatment-related Adverse Events based on the CTCAE v5.0 criteria reported by the study participants
Time frame: Day 1 - Day 100
Population: The safety population included all subjects exposed to MB02-SP, MB02-DM or US-Avastin®, and had at least one post dose safety assessment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MB02-SP (Bevacizumab Biosimilar) | Safety (Treatment-related Adverse Events) | Moderate (Grade 2) TEAES | 3 events |
| MB02-SP (Bevacizumab Biosimilar) | Safety (Treatment-related Adverse Events) | Unrelated TEAES (unlikely and not related) | 30 events |
| MB02-SP (Bevacizumab Biosimilar) | Safety (Treatment-related Adverse Events) | Life-Threatening (Grade 4) TEAEs | 0 events |
| MB02-SP (Bevacizumab Biosimilar) | Safety (Treatment-related Adverse Events) | Mild (Grade 1) TEAES | 39 events |
| MB02-SP (Bevacizumab Biosimilar) | Safety (Treatment-related Adverse Events) | Severe (Grade 3) TEAES | 0 events |
| MB02-SP (Bevacizumab Biosimilar) | Safety (Treatment-related Adverse Events) | Related TEAEs (possibly, probably and related TEAES) | 12 events |
| MB02-SP (Bevacizumab Biosimilar) | Safety (Treatment-related Adverse Events) | TEAEs | 42 events |
| MB02-DM (Bevacizumab Biosimilar) | Safety (Treatment-related Adverse Events) | Life-Threatening (Grade 4) TEAEs | 0 events |
| MB02-DM (Bevacizumab Biosimilar) | Safety (Treatment-related Adverse Events) | TEAEs | 58 events |
| MB02-DM (Bevacizumab Biosimilar) | Safety (Treatment-related Adverse Events) | Related TEAEs (possibly, probably and related TEAES) | 9 events |
| MB02-DM (Bevacizumab Biosimilar) | Safety (Treatment-related Adverse Events) | Unrelated TEAES (unlikely and not related) | 49 events |
| MB02-DM (Bevacizumab Biosimilar) | Safety (Treatment-related Adverse Events) | Mild (Grade 1) TEAES | 55 events |
| MB02-DM (Bevacizumab Biosimilar) | Safety (Treatment-related Adverse Events) | Moderate (Grade 2) TEAES | 3 events |
| MB02-DM (Bevacizumab Biosimilar) | Safety (Treatment-related Adverse Events) | Severe (Grade 3) TEAES | 0 events |
| US Licenced Avastin® | Safety (Treatment-related Adverse Events) | Related TEAEs (possibly, probably and related TEAES) | 6 events |
| US Licenced Avastin® | Safety (Treatment-related Adverse Events) | Severe (Grade 3) TEAES | 0 events |
| US Licenced Avastin® | Safety (Treatment-related Adverse Events) | Moderate (Grade 2) TEAES | 9 events |
| US Licenced Avastin® | Safety (Treatment-related Adverse Events) | TEAEs | 59 events |
| US Licenced Avastin® | Safety (Treatment-related Adverse Events) | Unrelated TEAES (unlikely and not related) | 53 events |
| US Licenced Avastin® | Safety (Treatment-related Adverse Events) | Life-Threatening (Grade 4) TEAEs | 0 events |
| US Licenced Avastin® | Safety (Treatment-related Adverse Events) | Mild (Grade 1) TEAES | 50 events |