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

• ClinicalTrials.gov Identifier: NCT04439929
• Recruitment Status: Completed
• First Posted: June 19, 2020
• Last Update Posted: June 19, 2020
• Sponsor: Turgut İlaçları A.Ş.
• Information provided by (Responsible Party): Turgut İlaçları A.Ş.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Healthy Participants	Biological: TUR01; Biological: Adalimumab-EU	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 168 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: 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
• Actual Study Start Date: July 17, 2019
• Actual Primary Completion Date: January 16, 2020
• Actual Study Completion Date: January 16, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Adalimumab-TUR01	Biological: TUR01; Administered as a single 40 mg, subcutaneous dose; Other Name: Adalimumab-Turgut
Active Comparator: Adalimumab-EU	Biological: Adalimumab-EU; Administered as a single 40 mg, subcutaneous dose; Other Name: Humira

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Immunogenicity - Incidence of anti-drug antibodies to adalimumab [ Time Frame: Day 1 - Day 71 ]
2. Immunogenicity - Incidence of neutralizing antibodies [ Time Frame: Day 1 - Day 71 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Germany

PAREXEL International GmbH, Early Phase Clinical Unit Berlin

Berlin, Germany, 14050

Sponsors and Collaborators

Turgut İlaçları A.Ş.

Investigators

• Principal Investigator: Rainard Fuhr; Parexel

More Information

• Responsible Party: Turgut İlaçları A.Ş.
• ClinicalTrials.gov Identifier: NCT04439929
• Other Study ID Numbers: 240648
• First Posted: June 19, 2020
• Last Update Posted: June 19, 2020
• Last Verified: June 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Turgut İlaçları A.Ş.:

adalimumab; biosimilar; healthy; phase 1; pharmacokinetics; bioequivalence

Additional relevant MeSH terms:

Adalimumab; Tumor Necrosis Factor Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents