Healthy VolunteersPhase 1NCT04238663
Pharmacokinetic Study Comparing MB02 And US And EU Avastin® In Healthy Male Volunteers
A Phase 1 study testing MB02 (Bevacizumab Biosimilar), EU approved Avastin® and US licenced Avastin® in people with Healthy Volunteers, run by mAbxience Research S.L. at 1 site in Germany.
Trial summary
Randomized, double blind, parallel group, single dose, 3 arm study to investigate and compare the pharmacokinetics (PK), safety and immunogenicity profile of MB02 with US and EU Avastin® in healthy male subjects. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- MB02 (Bevacizumab Biosimilar), EU approved Avastin® and US licenced Avastin®
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 115 participants
- Where
- 1 siteGermany
- Study dates
- 24 Sep 2019to 17 Mar 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Males of any race, between 18 and 55 years of age, inclusive, at Screening.
- Body mass index between 18.5 and 29.9 kg/m2, inclusive, at Screening and Check-in.
- Total body weight between 60 and 95 kg, inclusive, at Screening and Check-in.
- 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 nonhaemolytic hyperbilirubinemia [eg, Gilbert's syndrome] is acceptable) at Screening or Check-in as assessed by the Investigator (or designee).
- Relevant clinical laboratory evaluations of haematology, coagulation, urinalysis and clinical chemistry within the following ranges at Screening and Check in. A single repeat test will be allowed at each timepoint.
- Absolute neutrophil count ≥1.5 × 109 L
Show all 22Show fewer
- Platelet count ≥100 × 109 L
- Haemoglobin >10 g/dl
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ ULN
- Alkaline phosphatase (ALP) ≤1.5 × ULN
- Total bilirubin ≤ 1.5 ULN with direct bilirubin <20% in case of total bilirubin > ULN
- Blood urea nitrogen ≤1.5 × ULN
- Creatinine <132.63 µmol/L
- Serum albumin: ≥35 g/L
- Total cholesterol ≤ 7.75 mmol/L
- Triglycerides ≤ 3.42 mmol/L
- Creatine kinase (CK) ≤3 × ULN
- International normalised ratio (INR) 0.8 to 1.3
- Urine dipstick for proteinuria <2+
- Systolic blood pressure ≥90 mmHg and <140 mmHg and diastolic blood pressure ≥50 mmHg and <90 mmHg at Screening and Check in.
- Subjects agree to use contraception.
- 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.
Who cannot join
- 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).
- History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
- 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).
- 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.
- Presence of a nonhealing wound or fracture.
- Known history of clinically significant essential hypertension, orthostatic hypotension, fainting spells or blackouts for any reason, cardiac failure or history of thromboembolic conditions.
Show all 29Show fewer
- 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.
- Clinically relevant history of alcoholism, addiction or drug/chemical abuse prior to Check-in, and/or positive urinary test for alcohol or drugs of abuse at Screening or Check in.
- History of bleeding disorders or protein C, protein S, and/or factor V Leiden deficiency.
- History of clinically significant haemorrhage, epistaxis, GI bleeding, haemorrhoids and/or haemoptysis.
- History of GI perforation, ulcers, gastro oesophageal reflux, inflammatory bowel disease, diverticular disease, or any fistulae.
- 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.
- 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.
- 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.
- 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).
- 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.
- 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).
- Have received a live or attenuated vaccine from 3 months prior to Screening or have the intention to receive a vaccine during the study.
- Intend to travel to a region where a vaccination will be required due to endemic disease within 3 months of dosing.
- Previous treatment with an anti VEGF antibody or any other protein or antibody targeting the VEGF receptor.
- Use of tobacco- or nicotine-containing products within 1 year prior to Check-in, or positive cotinine test upon Screening or Check-in.
- Receipt of blood products within 60 days prior to Check-in.
- Donation of blood from 90 days prior to Screening, plasma from 14 days prior to Screening, or platelets from 42 days prior to Screening.
- Poor peripheral venous access.
- History of abnormal peripheral sensation including paraesthesia and/or numbness in arms and/or legs.
- Have previously completed or withdrawn from this study or any other study investigating bevacizumab, and/or have previously received bevacizumab.
- Subjects who, in the opinion of the Investigator (or designee), should not participate in this study.
- Vulnerable subjects (e.g. persons kept in detention).
- Subjects who are study site employees or immediate family members of a study site or Mabxience employee.
Trial locations and contacts
1 site in 1 country.
Germany1 site
Early Phase Clinical Unit (EPCU) PAREXEL International GmbH
Berlin, 14050
About this study
Official title: A Randomised, Double Blind, Three-Arm, Single Dose, Parallel Study To Compare the Pharmacokinetics, Safety and Immunogenicity of MB02 (Bevacizumab Biosimilar Drug), US Licenced Avastin® and EU Approved Avastin® in Healthy Male Volunteers
Randomized, double blind, parallel group, single dose, 3 arm study to investigate and compare the pharmacokinetics (PK), safety and immunogenicity profile of MB02 with US and EU 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.
Read the detailed description
The primary PK parameter endpoints are Cmax and AUC(0-∞) 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 versus EU Avastin®
- MB02 versus US Avastin®
- EU Avastin® 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 versus EU-approved Avastin®; MB02 versus US-licenced Avastin®; and EU-approved Avastin® versus US-licenced 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 anti-drug antibody [ADA] incidence and titers, and neutralising ADA results) will be listed. A summary of the number and percent of subjects testing positive for ADA or neutralising antibodies (NAB) before the dose of MB02, EU Avastin®, or US Avastin® (Day -1) and at scheduled postdose 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.
- Conditions
- Healthy Volunteers
- Being tested
- MB02 (Bevacizumab Biosimilar), EU approved Avastin®, US licenced Avastin®
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MB02 (Bevacizumab Biosimilar)Drug
Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion
EU approved Avastin®Drug
Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion
US licenced Avastin®Drug
Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion
| Study group | Role | What they receive |
|---|---|---|
| MB02 (Bevacizumab Biosimilar) | Experimental | Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. Receives: Drug: MB02 (Bevacizumab Biosimilar) |
| EU approved Avastin® | Active comparator | Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. Receives: Drug: EU approved Avastin® |
| US licenced Avastin® | Active comparator | Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. Receives: Drug: US licenced Avastin® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax: Maximum Observed Serum Concentration
To compare the pharmacokinetic (PK) profiles of MB02, US Avastin® and EU Avastin® (in terms of Cmax) to establish bioequivalence between the 3 study arms. For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) for the geometric LS means ratios are fully contained within the predefined bioequivalence limits of 0.80 to 1.25.
Measured: Predose, 1.5 hours (end of infusion), 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 3-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.
AUC(0-∞); Area Under the Serum Concentration-time Curve From Time Zero to Infinity
To compare the pharmacokinetic (PK) profiles of MB02, US Avastin® and EU Avastin® (in terms of AUC[0-∞]) to establish bioequivalence between the 3 study arms. For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) for the geometric least square means (GLSM) ratios are fully contained within the predefined bioequivalence limits of 0.80 to 1.25.
Measured: Predose, 1.5 hours (end of infusion), 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 3-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.
Secondary outcomes (6)
Tmax: Time of Maximum Observed Serum Concentration
To evaluate and compare the tmax of MB02, US Avastin® and EU Avastin® .
Measured: Predose, 1.5 hours (end of infusion), 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 3-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.
AUC(0 t)= Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Observable Concentration.
To evaluate and compare the AUC[0-t] of MB02, US Avastin® and EU Avastin®.
Measured: Predose, 1.5 hours (end of infusion), 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 3-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.
CL: Total Body Drug Clearance After IV Administration
To evaluate the CL of MB02, US Avastin® and EU Avastin®
Measured: Predose, 1.5 hours (end of infusion), 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 3-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.
t1/2: Apparent Serum Terminal Elimination Half-life
To evaluate the t1/2 of MB02, US Avastin® and EU Avastin®
Measured: Predose, 1.5 hours (end of infusion), 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 3-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.
Immunogenicity: Number of Participants With Anti-bevacizumab Antibodies (Including Neutralizing Antibodies)
Incidence of anti-bevacizumab antibodies (ADA), including neutralizing antibodies (Nab). Subjects who tested positive at baseline are not included here.
Rows for ADA and nAb are not mutually exclusive, i.e. a participant could be included in more than one Row.
Measured: Day -1, Day 14, Day 28, Day 56, and Day 78
Number of Participants With Treatment-emergent Adverse Events (Safety)
Compare the incidence of Treatment-emergent Adverse Events (TEAEs) reported in each treatment arm. TEAEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA version 22.0) and graded using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Measured: Day 1 - Day 100
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2020
- Study start24 Sep 2019
- Primary completion17 Mar 2020
- Study completion17 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 115 participants (actual)
Sponsor and investigators
- Lead sponsor
- mAbxience Research S.L.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Angela Sinn, MD, Principal investigator, Early Phase Clinical Unit (EPCU) PAREXEL International GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04238663
- Sponsor's protocol ID
- MB02 A 05 18
- Status last verified
- Mar 2021
- First submitted
- 16 Jan 2020
- Last updated
- 25 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Sinn A, Garcia-Alvarado F, Gonzalez V, Huerga C, Bullo F. A randomized, double blind, single dose, comparative study of the pharmacokinetics, safety and immunogenicity of MB02 (bevacizumab biosimilar) and reference bevacizumab in healthy male volunteers. Br J Clin Pharmacol. 2022 Mar;88(3):1063-1073. doi: 10.1111/bcp.15032. Epub 2021 Sep 4.
PubMed 34374114
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double Blind, Three-Arm, Single Dose, Parallel Study To Compare the Pharmacokinetics, Safety and Immunogenicity of MB02 (Bevacizumab Biosimilar Drug), US Licenced Avastin® and EU Approved Avastin® in Healthy Male Volunteers
- ClinicalTrials.gov ID
- NCT04238663
- Acronym / sponsor ID
- MB02 A 05 18
- Conditions
- Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 115 participants (actual)
- Lead sponsor
- mAbxience Research S.L.Industry (pharma, biotech, devices)
- Study start
- 24 Sep 2019 (actual)
- Primary completion
- 17 Mar 2020 (actual)
- Study completion
- 17 Mar 2020 (actual)
- First posted
- 23 Jan 2020 (actual)
- Results
- Posted 24 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Randomized, double blind, parallel group, single dose, 3 arm study to investigate and compare the pharmacokinetics (PK), safety and immunogenicity profile of MB02 with US and EU 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 AUC(0-∞) 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 versus EU Avastin®
- MB02 versus US Avastin®
- EU Avastin® 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 versus EU-approved Avastin®; MB02 versus US-licenced Avastin®; and EU-approved Avastin® versus US-licenced 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 anti-drug antibody [ADA] incidence and titers, and neutralising ADA results) will be listed. A summary of the number and percent of subjects testing positive for ADA or neutralising antibodies (NAB) before the dose of MB02, EU Avastin®, or US Avastin® (Day -1) and at scheduled postdose 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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MB02 (Bevacizumab Biosimilar) | Experimental | Drug: MB02 (Bevacizumab Biosimilar)Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. |
| EU approved Avastin® | Active comparator | Drug: EU approved Avastin®Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. |
| US licenced Avastin® | Active comparator | Drug: US licenced Avastin®Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (22 listed)
- Males of any race, between 18 and 55 years of age, inclusive, at Screening.
- Body mass index between 18.5 and 29.9 kg/m2, inclusive, at Screening and Check-in.
- Total body weight between 60 and 95 kg, inclusive, at Screening and Check-in.
- 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 nonhaemolytic hyperbilirubinemia [eg, Gilbert's syndrome] is acceptable) at Screening or Check-in as assessed by the Investigator (or designee).
- Relevant clinical laboratory evaluations of haematology, coagulation, urinalysis and clinical chemistry within the following ranges at Screening and Check in. A single repeat test will be allowed at each timepoint.
Key exclusion criteria (29 listed)
- 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).
- History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
- 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).
- 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.
- Presence of a nonhealing wound or fracture.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MB02 (Bevacizumab Biosimilar)Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion | Drug | MB02 (Bevacizumab Biosimilar) |
| EU approved Avastin®Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion | Drug | EU approved Avastin® |
| US licenced Avastin®Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion | Drug | US licenced Avastin® |
Primary outcome
Cmax: Maximum Observed Serum Concentration
Time frame: Predose, 1.5 hours (end of infusion), 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 3-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.
To compare the pharmacokinetic (PK) profiles of MB02, US Avastin® and EU Avastin® (in terms of Cmax) to establish bioequivalence between the 3 study arms. For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) for the geometric LS means ratios are fully contained within the predefined bioequivalence limits of 0.80 to 1.25.
AUC(0-∞); Area Under the Serum Concentration-time Curve From Time Zero to Infinity
Time frame: Predose, 1.5 hours (end of infusion), 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 3-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.
To compare the pharmacokinetic (PK) profiles of MB02, US Avastin® and EU Avastin® (in terms of AUC[0-∞]) to establish bioequivalence between the 3 study arms. For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) for the geometric least square means (GLSM) ratios are fully contained within the predefined bioequivalence limits of 0.80 to 1.25.
6 secondary outcomes
Tmax: Time of Maximum Observed Serum Concentration
Time frame: Predose, 1.5 hours (end of infusion), 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 3-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.
AUC(0 t)= Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Observable Concentration.
Time frame: Predose, 1.5 hours (end of infusion), 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 3-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.
CL: Total Body Drug Clearance After IV Administration
Time frame: Predose, 1.5 hours (end of infusion), 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 3-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.
t1/2: Apparent Serum Terminal Elimination Half-life
Time frame: Predose, 1.5 hours (end of infusion), 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 3-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.
Immunogenicity: Number of Participants With Anti-bevacizumab Antibodies (Including Neutralizing Antibodies)
Time frame: Day -1, Day 14, Day 28, Day 56, and Day 78
Number of Participants With Treatment-emergent Adverse Events (Safety)
Time frame: Day 1 - Day 100
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34374114Sinn A, Garcia-Alvarado F, Gonzalez V, Huerga C, Bullo F. A randomized, double blind, single dose, comparative study of the pharmacokinetics, safety and immunogenicity of MB02 (bevacizumab biosimilar) and reference bevacizumab in healthy male volunteers. Br J Clin Pharmacol. 2022 Mar;88(3):1063-1073. doi: 10.1111/bcp.15032. Epub 2021 Sep 4.
Related trials for Healthy Volunteers
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Not yet recruitingObservational study
Establishment of Biobank of Nasal Epithelium Samples From Healthy Volunteers
Healthy
RecruitingObservational study
Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives
Graft-Versus-Host Disease, Graft-versus-leukemia
Not yet recruitingObservational study
Screening Protocol
Pain
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Angela Sinn, MD principal investigator
Early Phase Clinical Unit (EPCU) PAREXEL International GmbH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MB02 (Bevacizumab Biosimilar), EU approved Avastin® and US licenced Avastin® in people with Healthy Volunteers, run by mAbxience Research S.L. at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cmax: Maximum Observed Serum Concentration (time frame: Predose, 1.5 hours (end of infusion), 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 3-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04238663, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2023.