A Randomized, Double-Blind, 3-arm Parallel Study to Compare PK, Safety, IMM and Tolerability of MB05, EU-sourced Synagis® and US-sourced Synagis®, as a Single Dose Intramuscular Injection in Healthy Volunteers.
Overview
- Phase
- Phase 1
- Intervention
- MB05 (Proposed palivizumab biosimilar)
- Conditions
- Healthy Volunteers
- Sponsor
- mAbxience Research S.L.
- Enrollment
- 150
- Locations
- 2
- Primary Endpoint
- Comparison of the Pharmacokinetic (PK) Profiles Between MB05 and EU-Synagis®, Between MB05 and US-Synagis® and Between EU-Synagis® and US-Synagis® in Terms of Area Under the Serum Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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
MB05 is being developed as a potential biosimilar to Synagis® for all indications for which Synagis® is approved. This study is designed to demonstrate PK similarity of the proposed biosimilar test product MB05 and the reference products EU- and US-Synagis®.This is a first-in-human study of the Synagis® biosimilar MB05. The reference product ynagis® was first approved by the US Food and Drug Administration (FDA) in 1998 and by the European Medicines agency (EMA) in 1999. As a proposed biosimilar, the clinical experience with Synagis® (as described in the Synagis® summary of product characteristics) (most recent versions) is deemed applicable to MB05.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy volunteers will be included in the study if they meet all of the following criteria at screening, and after check-in on Day -1 (prior to dose administration on Day 1):
- •Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
- •Adult male and female volunteers, 18 to 55 years of age (inclusive).
- •Body mass index (calculated) within the range of 18 to 30 kg/m2 inclusive and total body weight between 50 and 95 kg, inclusive, at screening and check-in.
- •Medically healthy without clinically significant abnormalities, including:
- •Physical examination without any clinically significant findings, in the opinion of the Investigator.
- •Systolic blood pressure (BP) in the range of 90 to 145 mm Hg (inclusive) and diastolic BP in the range of 50 to 90 mm Hg (inclusive) after at least 5 minutes in the supine position.
- •Pulse rate (PR) in the range of 40 to 100 beats/min (inclusive) after at least 5 minutes rest in a supine position.
- •Normal body temperature 35.1 to 37.6°C (inclusive) (Tympanic temperature).
- •Triplicate 12-lead electrocardiogram (ECG), taken after the volunteer has been supine for at least 5 minutes, with a QT interval corrected using the Fridericia method (QTcF) ≤ 450 msec for males and ≤ 470 msec for females and no clinically significant abnormalities, in the opinion of the Investigator.
Exclusion Criteria
- •Healthy volunteers will be excluded from the study if there is evidence of any of the following at screening or any time after check-in on Day -1 (prior to dose administration on Day 1):
- •Prior exposure to Synagis® (palivizumab).
- •Have a history of hypersensitivity or allergic reactions (either spontaneous or following drug administration) to any drug compound or its excipients, food, or other substance. Minor (non-anaphylactic) reactions to food substances (non-excipients) may be permitted, at the discretion of the Investigator.
- •Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, haematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, deemed to be clinically relevant as determined by the Investigator (or designee).
- •Presence or evidence of recent sunburn, scar tissue, tattoo (more than 25% of body area), open sore or branding that, in the opinion of the Investigator, would interfere with interpretation of skin adverse reactions.
- •Have a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) or human immunodeficiency virus (HIV). Screening only.
- •Have a positive test result for COVID-19 (polymerase chain reaction \[PCR\] or antigen test) within 72 hours prior to dose administration.
- •If subject smokes, subject is unwilling to abstain from smoking for 7 days prior to admission and during the confinement period.
- •Positive serum pregnancy test for women of childbearing potential (WOCBP) at the screening visit or positive urine pregnancy test with confirmatory serum pregnancy test prior to dosing on Day
- •Females who are breastfeeding.
Arms & Interventions
MB05 (Proposed palivizumab biosimilar)
Sterile vial 100mg/1ml, single-dose 3mg/kg administered as intramuscular injection on day 1.
Intervention: MB05 (Proposed palivizumab biosimilar)
EU-Synagis®
Sterile vial 100mg/1ml, single-dose 3mg/kg administered as intramuscular injection on day 1
Intervention: EU-Synagis®
US-Synagis®
Sterile vial 100mg/1ml, single-dose 3mg/kg administered as intramuscular injection on day 1
Intervention: US-Synagis®
Outcomes
Primary Outcomes
Comparison of the Pharmacokinetic (PK) Profiles Between MB05 and EU-Synagis®, Between MB05 and US-Synagis® and Between EU-Synagis® and US-Synagis® in Terms of Area Under the Serum Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf)
Time Frame: Day 1 - Day 100
Bioequivalence between MB05 and EU Synagis®, between MB05 and US-Synagis® and between EU-Synagis® and US-Synagis® will be investigated for AUC0-inf and Cmax by analysis of variance using log-transformed PK parameter values. Bioequivalence will be assessed by calculating the 90% CIs for the ratio of the least squares geometric means for each pairwise comparison and each PK parameter. Bioequivalence will be concluded where the 90% CIs for the ratio of least squares geometric means are contained within the range 80.00% to 125.00%. Blood samples collection timepoints: pre-dose (within 60 minutes prior); 4 hr (+/- 15 min); 12 hr (+/- 15 min); 24 hr (+/- 1 hr); 48 hr (+/- 5 hr); 72 hr (+/- 5 hr); 96 hr (+/- 5 hr); 120 hr (+/- 5 hr); 168 hr (+/- 5 hr) post-dose, and then at Days 15; 22; 29; 36; 43; 57; 71; 85; and 99 (end of study).
Compare the Pharmacokinetic (PK) Profiles Between MB05 and EU-Synagis®, Between MB05 and US-Synagis® and Between EU-Synagis® and US-Synagis® in Terms of Maximum Observed Serum Concentration Cmax.
Time Frame: Day 1 - Day 100
Bioequivalence between MB05 and EU Synagis®, between MB05 and US-Synagis® and between EU-Synagis® and US-Synagis® will be investigated for AUC0-inf and Cmax by analysis of variance using log-transformed PK parameter values. Bioequivalence will be assessed by calculating the 90% CIs for the ratio of the least squares geometric means for each pairwise comparison and each PK parameter. Bioequivalence will be concluded where the 90% CIs for the ratio of least squares geometric means are contained within the range 80.00% to 125.00%. Blood samples collection timepoints: pre-dose (within 60 minutes prior); 4 hr (+/- 15 min); 12 hr (+/- 15 min); 24 hr (+/- 1 hr); 48 hr (+/- 5 hr); 72 hr (+/- 5 hr); 96 hr (+/- 5 hr); 120 hr (+/- 5 hr); 168 hr (+/- 5 hr) post-dose, and then at Days 15; 22; 29; 36; 43; 57; 71; 85; and 99 (end of study).
Pharmacokinetics (PK)- (AUC0-inf)
Time Frame: Day 1 - Day 100
Pharmacokinetic (PK) profiles for each arm (AUC0-inf)
Pharmacokinetics (PK) - (Cmax)
Time Frame: Day 1 - Day 100
Pharmacokinetic (PK) profiles for each arm (Cmax)
Secondary Outcomes
- Tmax(Day 1 - Day 100)
- t1/2(Day 1 - Day 100)
- Vz(Day 1- Day 100)
- CL(Day 1- Day 100)
- Safety and Tolerability(Day 1- Day 100)
- Immunogenicity(Day 1- Day 100)