A Study Investigating the Safety, Absorption, and Elimination of MB04, a New Compound That May Potentially be Used in the Treatment of Autoimmune Disorders (MB04-A-01-23)

A Randomized, Double-blind, Three-part, Two-period, Two-sequence, Single-dose, Cross-over Study to Compare the Pharmacokinetics (PK), Safety and Immunogenicity Profile of MB04 (Proposed Etanercept Biosimilar), EU-sourced Enbrel® and US Licensed Enbrel® in Healthy Male Volunteers

This is a randomized, double-blind, three-part, two-sequence per part, two-period, single-dose, cross-over study in healthy male volunteers to compare the PK, safety, and immunogenicity of MB04 and EU /US Enbrel®.

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.

Study Overview

• Status: Recruiting
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: MB04; Drug: US License Enbrel; Drug: EU Source Enbrel

Detailed Description

The primary objective of the study is to demonstrate PK similarity between MB04 and EU-Enbrel®, between MB04 and US Enbrel® as well as between EU-Enbrel® and US-Enbrel®. Additional PK parameters will be evaluated as secondary endpoints.

Safety and tolerability will be assessed through Adverse Events, clinical laboratory, vital signs, ECGs, and physical examination findings, and any other parameter that is relevant for safety assessment.

The incidence of ADA to etanercept and the neutralizing potential and titre of positive ADA will be reported

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Susana Millan, PhD; Phone Number: +34 917 711 500; Email: Susana.Millan@mabxience.com
• Study Contact Backup: Name: Amalia Flórez; Phone Number: +34 917 711 500; Email: Amalia.Florez@mabxience.com

Study Locations

• Netherlands
  • Groningen, Netherlands, 9728 NZ
    • Recruiting
    • ICON Clinical Research Unit
    • Principal Investigator: Maria Velinova

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

1. BMI: 18.5 kg/m2 to 29.9 kg/m2, inclusive, at screening.
2. Weight: ≥60 kg to ≤100 kg, inclusive, at screening.
3. Status: healthy subjects.
4. Male subjects, if not surgically sterilized, must agree to use adequate contraception and not donate sperm from first admission to the clinical research center until 3 months after the last study drug administration. Adequate contraception for the male subject (and his female partner, if she is of childbearing potential) is defined as using hormonal contraceptives or an intrauterine device combined with at least 1 of the following forms of contraception: a diaphragm, a cervical cap, or a condom. Total abstinence from heterosexual intercourse, in accordance with the lifestyle of the subject, is also acceptable.
5. Ability and willingness to abstain from alcohol from 48 hours (2 days) prior to each study visit to the clinical research center.
6. Ability and willingness to abstain from methylxanthine-containing beverages or food (coffee, tea, cola, chocolate, energy drinks) and grapefruit (juice) from 48 hours (2 days) prior to each study visit to the clinical research center.
7. No presence of any clinically relevant abnormality identified by a detailed medical history and no clinically significant abnormal findings during screening, clinical examination, laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [eg, Gilbert's syndrome] is acceptable), vital signs, and 12-lead ECG.
8. Able to comprehend and willing to sign an ICF and to abide by the study restrictions. Subjects must have signed the ICF before any study-related procedure or evaluation is performed.

Exclusion Criteria

1. Previous participation in the current study.
2. Employee of ICON or the Sponsor.
3. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
4. Previous exposure to the study drug (etanercept).
5. History of sensitivity to latex.
6. History or presence of any disease or condition clinically relevant which might compromise the hemopoietic, renal, hepatic, endocrine, pulmonary (in light smokers, no signs or symptoms of chronic bronchitis: sputum, recurrent bronchitis or bronchospasm), central nervous, autonomic nervous, cardiovascular, immunological, dermatological, gastrointestinal, or any other body system or psychiatric disorder, as determined by the Investigator.
7. Any current or recent history of active infections, including localized infections (within 2 months prior to the screening visit for any serious infection which requires hospitalization or intravenous (IV) anti infective, and within 14 days prior to the screening visit for known coronavirus disease 2019 (COVID-19) infection (positive antigen or polymerase chain reaction [PCR] severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] test) or any active infection which requires anti-infective oral treatment).
8. History of tuberculosis (latent or active); have a positive QuantiFERON-TB Gold test during screening (if QuantiFERON-TB Gold test result is indeterminate, the subject will not be enrolled in this study).
9. Have the intention to travel to regions where tuberculosis and mycosis are endemic diseases within 3 months after dosing.
10. Receipt of live-attenuated or live vaccine within the last 2 months before randomization or planned vaccination (live vaccines) during the study period.
11. Receipt of COVID-19 vaccine within 2 months before randomization; or plans to receive a COVID-19 vaccine within 9 weeks after study first dosing; or presence of COVID-19 symptoms within 3 weeks prior to randomization.
12. Any clinically significant laboratory finding at the time of screening.
13. A negative result for human immunodeficiency virus (HIV) and hepatitis B and C is required for participation (if the subject shows a positive hepatitis B test compatible with prior immunization and not infection, the subject may be included at the discretion of the Investigator).
14. Current malignancy or malignancy within the last 5 years (with the exception of excised non melanoma skin cancer).
15. Active smokers, or who have smoked more than 5 cigarettes a day within the last 12 months prior to start of the study and who have no signs or symptoms of chronic bronchitis.
16. All prescribed medication must have been stopped at least 30 days prior to first admission to the clinical research center.
17. All over-the-counter medication, vitamin preparations and other food supplements, or herbal medications (eg, St. John's wort) must have been stopped at least 14 days prior to first admission to the clinical research center. An exception is made for paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs), which is allowed up to admission to the clinical research center.
18. Clinically relevant history of alcoholism, addiction or drug/chemical abuse prior to screening, and/or positive alcohol and/or drug test screen confirmed by repeat at screening or check-in.
19. Donation or loss of more than 450 mL of blood within 60 days prior to the first drug administration. Donation or loss of more than 1.5 L of blood in the 10 months prior to the first drug administration in the current study.
20. Participation in a drug study within 30 days prior to the first drug administration in the current study. Participation in 4 or more other drug studies in the 12 months prior to the first drug administration in the current study.
21. Presence of tattoo or scars or any type of skin lesions at the proposed site of injection, that is interfering with the abdominal injection.
22. Subjects who, in the opinion of the Investigator, should not participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MB04 (etanercept biosimilar); 1 mL pre-filled single-use syringe containing 50 mg (50mg/mL) of etanercept	Drug: MB04; Subcutaneous injection; Other Names: (etanercept biosimilar)
Active Comparator: US licensed Enbrel (etanercept); 1 mL pre-filled single-use syringe containing 50 mg (50mg/mL) of etanercept	Drug: US License Enbrel; Subcutaneous injection; Other Names: (etanercept)
Active Comparator: EU sourced Enbrel (etanercept); 1 mL pre-filled single-use syringe containing 50 mg (50mg/mL) of etanercept	Drug: EU Source Enbrel; Subcutaneous injection; Other Names: (etanercept)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the serum concentration versus time curve (AUC) from time zero to infinity (AUC0-inf)	Predose and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312, 408, and 600 h post dose	Day 1 to day 62
Maximum observed serum concentration (Cmax)	Predose and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312, 408, and 600 h post dose	Day 1 to day 62

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC from time zero to the last quantifiable concentration (AUC0-last)	Predose and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312, 408, and 600 h post dose	Day 1 to day 62
Time to reach Cmax (tmax)	Predose and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312, 408, and 600 h post dose	Day 1 to day 62
Total body clearance (CL/F)	Predose and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312, 408, and 600 h post dose	Day 1 to day 62
Terminal half-life (t½)	Predose and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312, 408, and 600 h post dose	Day 1 to day 62
Incidence of anti-etanercept antibodies (ADA) and neutralizing antibodies (Nab)	Predose and, on Days 7, 14, and 26	Day 1 to day 62

Collaborators and Investigators

• Sponsor: mAbxience Research S.L.

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2024
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: March 11, 2024
• First Submitted That Met QC Criteria: April 26, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Etanercept
• Other Study ID Numbers: MB04-A-01-23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes