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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Participants

Intervention / Treatment
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* Biological: TUR01
* Biological: Adalimumab-EU


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adalimumab-TUR01<br> | Biological: TUR01<br>* Administered as a single 40 mg, subcutaneous dose<br>* Other names: Adalimumab-Turgut;|
| Active Comparator: Adalimumab-EU<br> | Biological: Adalimumab-EU<br>* Administered as a single 40 mg, subcutaneous dose<br>* Other names: Humira;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adalimumab, biosimilar, healthy, phase 1, pharmacokinetics, bioequivalence