Pharmacokinetic Study Comparing MB05 (Proposed Palivizumab Biosimilar), EU-sourced Synagis® and US-sourced Synagis® in Healthy Volunteers.

• Status: Not yet recruiting
• Trial end date: 2022-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Randomized, double blind, parallel group, single dose, 3 arm study to investigate and compare the pharmacokinetics (PK), safety, immunogenicity and tolerability of MB05 with US and EU Synagis® in healthy 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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: mAbxience S.A
• Treatments: Palivizumab

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 60 years of age (inclusive).

3. Body mass index (calculated) within the range of 18 to 30 kg/m2 inclusive and weight ≥ 55 kg.

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. Heart rate (HR) in the range of 55 to 100 beats/min (inclusive) after at least 5 minutes rest in a supine position.

4. Normal body temperature 36.5 to 37.5°C (inclusive).

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 as defined by:

• Absolute neutrophil count ≥ 1.5 x 109/L

• Platelet count ≥ 100 x 109/L

• Haemoglobin > 10 g/dl

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). Note: in the event the urinary drug test is positive, the test may be repeated once (at the discretion of the PI) to confirm eligibility.

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 agree not to donate ova, not to attempt to become pregnant, and, if engaging in sexual intercourse with a male partner must agree to use an acceptable method of contraception (refer to APPENDIX 4) for from signing the consent form until at least 100 days after the last dose of study drug.

8. Male volunteers, must agree not to donate sperm for at least 100 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 with a female who may become pregnant, must agree to have the female use an acceptable form of contraception (refer to APPENDIX 4) from signing the consent form until at least 100 after the last dose of study drug.

9. Have suitable venous access for blood sampling. Be willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.

Exclusion Criteria:

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.

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 or human immunodeficiency virus (HIV). Screening only.

6. Smoke more than 2 cigarettes or equivalent per week. Note: subjects who smoke less than 2 cigarettes per week can be included in the study but must be willing to abstain from smoking 7 days prior to admission and during the confinement period.

7. 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.

8. Females who are breastfeeding.

9. Have a history of cancer including lymphoma, leukaemia and skin cancer (volunteers with a maximum of 1 surgically resected basal cell carcinoma or squamous cell carcinoma are permitted).

10. Have an illness within 30 days prior to screening, or prior to dosing, that is classed as clinically significant by the Investigator.

11. Any clinically significant infection, in the opinion of the Investigator, ongoing at screening or admission to the clinical unit.

12. 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.

13. Have participated in another clinical study of 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.

14. Have had major surgery within 30 days prior to screening or will have an operation between screening and the end of study visit, or have any unhealed wound, including wound dehiscence and wound healing complications requiring medical intervention.

15. Have donated > 100 mL blood within 4 weeks prior to the administration of the study drug.

16. 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 women of childbearing potential (WOCBP) are permitted.

2. Paracetamol (up to a maximum of 4 doses of 500 mg per day, and no more than 3g per week) is permitted.

3. Ibuprofen (up to a maximum of 4 doses of 200 mg per day) is permitted.

17. 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.

18. Any person who is an employee of an Investigator or Sponsor, or an immediate relative of an Investigator.

19. 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.