Adalimumab PK Bioequivalence Study to EU and US Sourced Humira

Single Center, Randomized, Double-Blind, 3-Way Parallel Study to Compare the Pharmacokinetics, Safety and Tolerability of BMO-2 to EU and US Sourced Humira, Administered as a Single Dose (40 mg) Subcutaneous Injection in Healthy Adults

Double-Blind, 3-Way Parallel Study to Compare the Pharmacokinetics, Safety and Tolerability of BMO-2 to EU and US Sourced Humira® Administered as a Single Dose (40 mg) Subcutaneous Injection in Healthy Adults.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Biological: BMO-2; Biological: EU-Humira; Biological: US-Humira

Detailed Description

This is a single-center, randomized, double-blind, 3-way parallel study in 270 healthy adult male and female subjects. During this study, the PK bioequivalence of BMO-2, containing 40 mg adalimumab, will be compared to EU licensed Humira® (EU-Humira® ) (40 mg) and US licensed Humira® (US-Humira® ) (40 mg).

Randomization will be stratified by body weight (weight categories of 60.0-79.9 kg and 80.0-95.0 kg). After randomization, subjects will receive one of the following treatments: a single sc injection of 40 mg BMO-2, an equivalent sc injection of EU-Humira® (40 mg), or an equivalent sc injection of US-Humira® (40 mg).

Volunteers participation in the study is expected to finish with the follow-up visit, scheduled 70 days after the injection of study drug.

• Study Type: Interventional
• Enrollment (Actual): 270
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium
    • SGS Belgium NV

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Weight: 60.0-95.0 kg.
• Body mass index (BMI) : 19.0-30.0 kg/m2, inclusive
• Medical history without major pathology.
• Systolic blood pressure ≤150 mmHg and diastolic blood pressure ≤90 mmHg.
• Computerized (12-lead) electrocardiogram (ECG) recording without signs of clinically relevant pathology
• Nonsmoker or light smoker
• Ability and willingness to abstain from alcohol from 48 h prior to drug administration and 48h prior to ambulatory visits, and during the stays in the clinical research center until discharge from the in-house period.
• Fertile males and females participating in heterosexual sexual relations:willingness to use adequate contraception from screening until 90 days after the follow-up visit
• Females must not lactate and must have a negative pregnancy test at screening and at admission
• Differentiation of leukocytes, platelet count, hematocrit and hemoglobin results within the reference ranges. Minor deviations considered to lack any clinical relevance by the Principal Investigator can be accepted.
• All other values for hematology and for biochemistry tests of blood and urine within the normal range or showing no clinically relevant deviations as judged by the Principal Investigator.

Other protocol-defined inclusion/exclusion criteria may apply

Exclusion Criteria:

• History of relevant drug and/or food allergies.
• Hypersensitivity to Humira® or its constituents.
• Known history of previous exposure to anti TNF-alpha molecules.
• Any past or concurrent medical conditions potentially increasing the subject's risks. Examples of these include medical history with evidence of clinically relevant pathology (e.g., malignancies, demyelinating disorders).
• Presence of chronic obstructive pulmonary disease (COPD). Asthma in the childhood is allowed
• Any current active infections, including localized infections, or any recent history
• Treatment with non-topical medications (including over the counter medication, and herbal remedies such as St. John's Wort extract) within 7 days prior to study drug administration, with the exception of hormonal contraceptives, multivitamins, vitamin C, food supplements and a limited amount of acetaminophen, which may be used throughout the study.
• History of active tuberculosis or presence of active or latent tuberculosis.
• Having resided or traveled in regions where tuberculosis and mycosis are endemic within 90 days before screening, or who intend to visit such a region during the period of 3 months after dosing.
• Having received live vaccines during the past 4 weeks before screening or have the intention to receive vaccination during the study.
• Participation in a drug study within 60 days or 5 half-lives of the previous drug (if known), whichever is longer, prior to drug administration
• Donation of more than 500 mL of blood within 8 weeks prior to drug administration.
• History of alcohol abuse or drug addiction (including soft drugs like cannabis products).
• Positive urine drug screen (opiates, methadone, cocaine, amphetamines (including XTC or metamphetamines), cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants) and positive alcohol breath test.
• Positive screen on Hepatitis B surface antigen (HBsAg), anti-Hepatitis C virus antibodies (HCV), or anti-human immunodeficiency virus 1/2 antibodies (HIV).

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A; Single Injection of 40mg / 0.8 mL BMO-2	Biological: BMO-2; Volunteers randomized in Treatment A will receive a single subcutaneous injection of BMO-2 (40mg / 0.8mL).; Other Names: Adalimumab
Active Comparator: Treatment B; Single Injection of 40mg / 0.8 mL EU-Humira	Biological: EU-Humira; Volunteers randomized in Treatment B will receive a single subcutaneous injection of EU-Sourced Humira (40 mg / 0/8 mL); Other Names: Adalimumab
Active Comparator: Treatment C; Single Injection of 40mg / 0.8 mL US-Humira	Biological: US-Humira; Volunteers randomized in Treatment C, will receive a single subcutaneous injection of US-sourced Humira (40 mg / 0.8 mL).; Other Names: Adalimumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration versus time curve (AUC) of adalimumab.	1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71 days post subcutaneous injection.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Adverse Events		Up to 71 days.
Safey variable - Tolerability (injection site reactions)	Tolerability assessments as measured by injection site reactions	Predose and 1, 2, 3, 7, 9, 36, and 71 days post subcutaneous injection.
Safety variable - immunogenicity (Presence of anti-adalimumab antibodies)	Presence of anti-adalimumab antibodies	Day 1 (pre-dose) and Day 9, 29, and 71 days post subcutaneous injection.

Collaborators and Investigators

• Sponsor: Mylan Inc.
• Collaborators: Mylan GmbH
• Investigators: Principal Investigator: Magdalena Petkova, MD, SGS Belgium NV; Study Director: Fausto Berti, Mylan GmbH

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: June 3, 2015
• First Submitted That Met QC Criteria: June 15, 2015
• First Posted (Estimate): June 16, 2015

Study Record Updates

• Last Update Posted (Actual): March 11, 2022
• Last Update Submitted That Met QC Criteria: March 9, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Adalimumab; Biosimilar Pharmaceuticals
• Additional Relevant MeSH Terms: Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: MYL-HEB-1001; 2014-000212-33 (EudraCT Number)