NCT04408989UnknownPhase 1
A Randomized, Double-Blind, Three-Arm, Single Dose, Parallel Study To Compare the Pharmacokinetics, Safety and Immunogenicity of MB02-SP, MB02-DM (Bevacizumab Biosimilar Drugs)and US-licensed Avastin® in Healthy Male Volunteers
mAbxience Research S.L.2 sites in 1 country114 target enrollmentStarted: August 12, 2020Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Sponsor
- Enrollment
- 114
- Locations
- 2
- Primary Endpoint
- Pharmacokinetics (PK) - (AUC[0-∞])
Study Overview
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®.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •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.
- •Total body weight between 50 and 95 kg, inclusive, at Screening.
- •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).
- •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+
- •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.
Exclusion Criteria
- •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.
- •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 alcohol breath test and/or urinary drug test screen (confirmed by repeat) 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.
Arms & Interventions
MB02-SP (Bevacizumab Biosimilar)
Experimental
Sterile vial 100mg/4ml, single-dose 1mg/kg administered as 90-minute infusion on day 1.
Intervention: MB02-SP (Drug)
MB02-DM (Bevacizumab Biosimilar)
Experimental
Sterile vial 100mg/4ml, single-dose 1mg/kg administered as 90-minute infusion on day 1.
Intervention: MB02-DM (Drug)
US licenced Avastin®
Active Comparator
Sterile vial 100mg/4ml, single-dose 1mg/kg administered as 90-minute infusion on day 1.
Intervention: US licenced Avastin® (Drug)
Outcomes
Primary Outcomes
Pharmacokinetics (PK) - (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
Compare the pharmacokinetic (PK) profiles of the 3 arms (AUC\[0-∞\])
Pharmacokinetics (PK) - (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
Compare the pharmacokinetic (PK) profiles of the 3 arms (Cmax)
Secondary Outcomes
- 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)
- 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)
- 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)
- 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)
- Immunogenicity(Days -1, 14, 28, 56 and 78)
- Safety (Number of Participants Reporting Treatment-related Adverse Events)(Day 1 - Day 100)
- Safety (Treatment-related Adverse Events)(Day 1 - Day 100)
Investigators
Study Sites (2)
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