Comparative Pharmacokinetic, Safety, Tolerability and Immunogenicity Study of Adalimumab in Healthy Subjects

A Randomized, Double-blind, Two-arm, Parallel Group, Single-dose Study to Compare the Pharmacokinetics, Safety, Tolerability, and Immunogenicity of Two Formulations of Adalimumab (TUR01 and EU Sourced Humira®) in Healthy Subjects

This is a randomized, double-blind, two-arm, parallel group, single-dose study to demonstrate pharmacokinetic, safety, tolerability and immunogenicity similarity of biosimilar candidate TUR01 to EU-sourced Humira® in healthy participants after administration of adalimumab.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Biological: TUR01; Biological: Adalimumab-EU

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • Parexel International GmbH, Early Phase Clinical Unit Berlin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy female subjects of non-childbearing potential or healthy male subjects aged 18 to 55 years (inclusive at screening).
• Have body weight between 65.0 to 90.0 kg and a body mass index between 20.0 to 29.9 kg/m2, inclusive.
• Must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
• Must be able to provide written informed consent, which must be obtained prior to any study related procedures.

Exclusion Criteria:

• Evidence or history of clinically significant or relevant pathology.
• Have either active or latent tuberculosis.
• Have received treatment with a monoclonal antibody or fusion protein within 9 months prior to administration and/or have evidence of immunogenicity from previous exposure to a monoclonal antibody or fusion protein.
• Have a mental disease classified as serious by the Investigator.
• Have received live vaccine(s) within 4 weeks prior to Screening or who will require live vaccine(s) between Screening and the final study visit.
• Who intake alcoholic beverages more than 28 units per week.
• Have taken medication with a half-life of > 24 h within 4 weeks or 10 half-lives of the medication prior to investigational medicinal product administration.
• Have donated > 100 mL of blood or plasma within 4 weeks prior to investigational medicinal product administration.
• Have participated in another study with an investigational drug within 4 weeks prior to investigational medicinal product administration. Subjects who have received treatment with a biological or immunosuppressive agent within 3 months of screening should also be excluded.
• Subjects who are not able to consume standardized meals provided by the clinical study site during hospitalization.
• Subjects who, in the opinion of the Investigator, are not likely to complete the study for whatever reason.
• Involvement of any sponsor, study site/contract research organisation employee, Investigator or their close relatives.
• Vulnerable subjects.
• Pregnant or nursing women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Adalimumab-TUR01	Biological: TUR01; Administered as a single 40 mg, subcutaneous dose; Other Names: Adalimumab-Turgut
ACTIVE_COMPARATOR: Adalimumab-EU	Biological: Adalimumab-EU; Administered as a single 40 mg, subcutaneous dose; Other Names: Humira

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the concentration-time curve from time 0 to infinity (AUCinf)	AUCinf = area under the concentration-time curve from time zero to the last quantifiable concentration (AUClast) + last observed concentration (Ct)/terminal rate constant (λz)	Day 1 - Day 71
Maximum serum concentration (Cmax)	Cmax	Day 1 - Day 71

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the concentration-time curve from time zero to the last quantifiable concentration (AUClast)		Day 1 - Day 71
Area under the concentration-time curve from time zero to 336 hours (AUC336)	Area under the concentration-time curve from time zero to 14 days	Day 1 - Day 15
Area under the concentration-time curve from time zero to 672 hours (AUC672)	Area under the concentration-time curve from time zero to 28 days	Day 1 - Day 29
Area under the concentration-time curve from time zero to 1008 hours (AUC1008)	Area under the concentration-time curve from time zero to 42 days	Day 1 - Day 43
Area under the concentration-time curve from time zero to 1680 hours (AUC1680)	Area under the concentration-time curve from time zero to 70 days	Day 1 - Day 71
Time to Cmax (Tmax)	Time to reach the maximum concentration	Day 1 - Day 71
Apparent volume of distribution based on the terminal phase (Vz/F)		Day 1 - Day 71
Terminal rate constant (λz)	The parameter will be calculated by linear least squares regression analysis using at least 3 non-zero concentrations in the terminal phase	Day 1 - Day 71
Terminal half-life calculated by ln(2)/λz (t½)		Day 1 - Day 71
Apparent total body clearance (CL/F)		Day 1 - Day 71
Area under the concentration-time curve extrapolated from time t to infinity as a percentage of total AUC (%AUCextrap)		Day 1 - Day 71

Other Outcome Measures

Outcome Measure	Time Frame
Immunogenicity - Incidence of anti-drug antibodies to adalimumab	Day 1 - Day 71
Immunogenicity - Incidence of neutralizing antibodies	Day 1 - Day 71

Collaborators and Investigators

• Sponsor: Turgut İlaçları A.Ş.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 17, 2019
• Primary Completion (ACTUAL): January 16, 2020
• Study Completion (ACTUAL): January 16, 2020

Study Registration Dates

• First Submitted: June 15, 2020
• First Submitted That Met QC Criteria: June 17, 2020
• First Posted (ACTUAL): June 19, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 19, 2020
• Last Update Submitted That Met QC Criteria: June 17, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: pharmacokinetics; phase 1; bioequivalence; adalimumab; healthy; biosimilar
• Additional Relevant MeSH Terms: Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: 240648

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No