Clinical trial NCT05121246: A PK Study Comparing MB05, EU-sourced Synagis® and US-sourced Synagis® in Healthy Volunteers.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: mAbxience Research S.L.
Sponsor class: INDUSTRY
First posted: 2021-11-16
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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):

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.
2. Adult male and female volunteers, 18 to 55 years of age (inclusive).
3. 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.
4. Medically healthy without clinically significant abnormalities, including:

   1. Physical examination without any clinically significant findings, in the opinion of the Investigator.
   2. 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.
   3. Pulse rate (PR) in the range of 40 to 100 beats/min (inclusive) after at least 5 minutes rest in a supine position.
   4. Normal body temperature 35.1 to 37.6°C (inclusive) (Tympanic temperature).
   5. 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.
   6. Adequate bone marrow function defined by absolute neutrophil count, platelet count and haemoglobin levels within normal ranges (per local laboratory standard).
   7. Adequate liver function as defined by:

      • Alanine aminotransferase (ALT) aspartate aminotransferase (AST), alkaline phosphatase (ALP) and bilirubin ≤ 1.5 x upper limit of normal (ULN). Note: Bilirubin \> 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin is \< 35%.
   8. Adequate coagulation, as defined by:

      • Prothrombin time (PT) / International Normalised Ratio (INR), thrombin time (TT), or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN.
   9. Adequate renal function, as defined by:

      • Creatinine or measured or calculated creatinine clearance ≤ 1.5 x ULN. Note. Glomerular filtration rate (GFR) can be used in place of creatinine or CrCl.
   10. No other clinically significant findings in serum chemistry, haematology, coagulation and urinalysis examinations, in the opinion of the Investigator.

   Note. The above assessments may be repeated once, if abnormal values were recorded in the first instance, at the discretion of the Investigator.
5. No prior history of chronic alcohol abuse or excessive alcohol intake, at the discretion of the PI, within 12 weeks prior to screening, and negative alcohol test results (at screening and on Day -1). Excessive alcohol intake is defined as regular consumption of \> 12 standard units of alcohol per week, or more than 4 standard drinks on \> 3 days per week, where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer \[4.9% Alc./Vol\], 100 mL wine \[12% Alc./Vol\], 30 mL spirit \[40% Alc./Vol\]).
6. No prior history of substance abuse or drug addiction within 12 months prior to first study drug administration and negative drug test results (at screening and on Day -1).
7. Female volunteers must:

   1. Be of non-childbearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before the Screening visit) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone \[FSH\] level indicative of postmenopausal status per local laboratory definition), OR
   2. If of childbearing potential:

      * Must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test within 24 hours prior to dose administration on Day 1
      * Must not be breastfeeding, lactating or planning pregnancy during the study period
      * Must agree not to attempt to become pregnant
      * If not exclusively in same-sex relationships, must agree to use adequate contraception (which is defined as use of a condom by the male partner combined with the use of a highly effective method of contraception per APPENDIX 4) from 30 days prior to dosing until at least 190 days after the last dose of study drug.
      * Must agree not to donate ova for at least 190 days after the last dose of study drug.
8. Male volunteers, must agree not to donate sperm for at least 190 days after the last dose of study drug, and if engaging in sexual intercourse, must agree to:

   1. use a condom, PLUS
   2. when engaging in sexual intercourse with a female who may become pregnant, must agree to have the female use an acceptable form of contraception (refer to APPENDIX 4) from 30 days prior to dosing until at least 190 days after the last dose of study drug.
9. Have suitable venous access for blood sampling.
10. Be willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.

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):

1. Prior exposure to Synagis® (palivizumab).
2. 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.
3. 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).
4. 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.
5. Have a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) or human immunodeficiency virus (HIV). Screening only.
6. Have a positive test result for COVID-19 (polymerase chain reaction \[PCR\] or antigen test) within 72 hours prior to dose administration.
7. If subject smokes, subject is unwilling to abstain from smoking for 7 days prior to admission and during the confinement period.
8. 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 1.
9. Females who are breastfeeding.
10. Have a history of cancer including lymphoma, leukaemia and skin cancer (volunteers with surgically resected basal cell carcinoma or squamous cell carcinomas are permitted).
11. Have an illness within 30 days prior to screening, or prior to dosing, that is classed as clinically significant by the Investigator.
12. Any clinically significant infection, in the opinion of the Investigator, ongoing at screening or admission to the clinical unit.
13. Prior exposure to any investigational monoclonal antibody within 6 months or 5 half-lives of the previous drug (if known), whichever is longer, prior to study drug administration.
14. Have been dosed in another clinical study with an investigational drug (excluding monoclonal antibody) within 30 days or 5 half-lives of the investigational drug (whichever is longer) prior to the administration of the study drug or are currently participating in another clinical study of an investigational drug or intending to participate in another clinical study of an investigational drug before completion of all scheduled evaluations in this clinical study.
15. Have had major surgery within 30 days prior to screening or will have an operation between screening and the end of study visit.
16. Have donated \> 100 mL blood or plasma within 4 weeks prior to the administration of the study drug. Participant must also agree to refrain from donating blood or blood products throughout the duration of the study.
17. Use of any prescription or over-the-counter medication (including herbal products, diet aids, and hormone supplements) within 10 days or 5 half-lives of the medication (whichever is longer) prior to the first study drug administration, which, in the opinion of the Investigator, could affect the outcome of the study. The following exceptions apply:

    1. Contraceptives for WOCBP.
    2. Paracetamol (up to a maximum of 4 doses of 500 mg per day, and no more than 3g per week).
    3. Ibuprofen (up to a maximum of 4 doses of 200 mg per day).
18. Has received (or plans to receive) a vaccine within the following timeframes:

    1. Live or attenuated vaccine within 3 months prior to dose administration on Day 1 or plans to receive a live or live attenuated vaccine during the study.
    2. Other vaccines (including COVID-19 vaccines) within 14 days prior to dose administration on Day 1 or plans to receive other vaccines within 14 days following dose administration on Day 1.
19. Any person who is an employee of an Investigator or Sponsor, or an immediate relative of an Investigator.
20. Any other condition or prior therapy that in the opinion of the Investigator would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.

Primary outcomes:
measure: 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)
timeFrame: Day 1 - Day 100
measure: 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.
timeFrame: Day 1 - Day 100
measure: Pharmacokinetics (PK)- (AUC0-inf)
timeFrame: Day 1 - Day 100
measure: Pharmacokinetics (PK) - (Cmax)
timeFrame: Day 1 - Day 100
Secondary outcomes:
measure: Tmax
timeFrame: Day 1 - Day 100
measure: t1/2
timeFrame: Day 1 - Day 100
measure: Vz
timeFrame: Day 1- Day 100
measure: CL
timeFrame: Day 1- Day 100
measure: Safety and Tolerability
timeFrame: Day 1- Day 100
measure: Immunogenicity
timeFrame: Day 1- Day 100
Other outcomes:
Locations:
city: Brisbane
country: Australia
facility: Nucleus Network. Q-Pharm Pty Ltd
state: Queensland
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research Ltd.
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research Ltd.
Study officials:
References: