A Trial to Compare the Pharmacokinetics of Tralokinumab in Healthy Subjects

• ClinicalTrials.gov Identifier: NCT04674826
• Recruitment Status: Completed
• First Posted: December 19, 2020
• Last Update Posted: January 5, 2022
• Sponsor: LEO Pharma
• Information provided by (Responsible Party): LEO Pharma

Study Description

Brief Summary:

The purpose of this trial is to compare the pharmacokinetics (PK), safety, tolerability and immunogenicity of a single dose of 300 mg tralokinumab administered as a 1 × X mL subcutaneous (SC) injection with Device A and 2 × Y mL consecutive SC injections with Device B.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Tralokinumab administered as 1 × X mL with Device A; Device: Tralokinumab administered as 2 × Y mL with Device B	Phase 1

Detailed Description:

This is a single center, randomized, open label, 2 period, 2 sequence cross over trial designed to compare the PK and to evaluate the safety, tolerability and immunogenicity of 300 mg tralokinumab administered as a 1 × X mL SC injection with Device A (test treatment [T]) and 2 × Y mL consecutive SC injections with Device B (reference treatment [R]) in healthy subjects. Additionally, the experience of tralokinumab being administered with Device A compared to Device B will be evaluated.

After being informed about the study and the potential risks, all subjects giving written informed consent will be enrolled and randomized to 1 of 2 treatment sequences, Sequence TR or Sequence RT in a 1:1 ratio (i.e., subjects receive the 2 treatments in the specified order).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 101 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-label, 2-period, 2-sequence Cross-over Trial to Compare the Pharmacokinetics of Tralokinumab of Two Presentations in Healthy Subjects
• Actual Study Start Date: February 8, 2021
• Actual Primary Completion Date: December 29, 2021
• Actual Study Completion Date: December 29, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: TR (Test-Reference); Treatment period 1: 300 mg tralokinumab, single subcutaneous dose, 1 × X mL Device A (Test treatment, T) Treatment period 2: 300 mg tralokinumab, subcutaneous dose, 2 × Y mL Device B (Reference treatment, R)	Drug: Tralokinumab administered as 1 × X mL with Device A; Tralokinumab is a human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. It is presented as a liquid formulation for subcutaneous (SC) administration; Device: Tralokinumab administered as 2 × Y mL with Device B; Tralokinumab is a human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. It is presented as a liquid formulation for subcutaneous (SC) administration
Experimental: RT (Reference-Test); Treatment period 1: 300 mg tralokinumab, subcutaneous dose, 2 × Y mL Device B (Reference treatment, R) Treatment period 2: 300 mg tralokinumab, single subcutaneous dose, 1 × X mL Device A (Test treatment, T)	Drug: Tralokinumab administered as 1 × X mL with Device A; Tralokinumab is a human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. It is presented as a liquid formulation for subcutaneous (SC) administration; Device: Tralokinumab administered as 2 × Y mL with Device B; Tralokinumab is a human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. It is presented as a liquid formulation for subcutaneous (SC) administration

Outcome Measures

Primary Outcome Measures :

1. Area under the serum concentration time curve from time 0 (pre dose) extrapolated to infinity (AUC0-inf) in each Treatment Period derived from all observed concentrations in the time period pre dose to 16 weeks post dose [ Time Frame: In each Treatment Period pre-dose to 16 weeks post dose ]
2. Area under the serum concentration time curve from time 0 (pre dose) to time of last quantifiable concentration in each Treatment Period derived from all observed concentrations in the time period pre dose to 16 weeks post dose. [ Time Frame: In each Treatment Period pre-dose to 16 weeks post dose ]
3. Observed maximum serum concentration (Cmax) in each Treatment Period derived from all observed concentrations in the time period pre dose to 16 weeks post dose [ Time Frame: In each Treatment Period pre-dose to 16 weeks post dose ]

Secondary Outcome Measures :

1. Time corresponding to observed maximum serum concentration (tmax) [ Time Frame: In each Treatment Period pre-dose to 16 weeks post dose ]
2. Terminal half life (t½) in each Treatment Period derived from all observed concentrations in the time period pre dose to 16 weeks post dose [ Time Frame: In each Treatment Period pre-dose to 16 weeks post dose ]
3. Apparent total body clearance (CL/F), calculated as dose/AUC0-inf [ Time Frame: In each Treatment Period pre-dose to 16 weeks post dose ]
   (AUC0-inf: Area under the serum concentration time curve from time 0 (pre dose) extrapolated to infinity)
4. Apparent volume of distribution based on terminal phase (Vz/F), calculated as t½/ln(2)*CL/F [ Time Frame: In each Treatment Period pre-dose to 16 weeks post dose ]
   (t½: Terminal half life; CL/F: Apparent total body clearance)
5. Number of treatment emergent adverse events (TEAEs) from Day 1 to Day 126 and of TEAEs from Day 127 to Day 239 (number of adverse events [AEs] emerging with each treatment) [ Time Frame: Day 1 to Day 239 ]
6. Presence of binding and neutralizing anti-drug antibodies (ADAs) at Days 1 (pre dose), 15, and 57 of Treatment Periods 1 and 2 and Day 239 [ Time Frame: Day 1 to Day 239 ]

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 male or female aged 18 to 55 years (both included) at the time of Screening.
• Female subjects of childbearing potential must use a highly effective form of birth control throughout the trial and at least for 16 weeks after last administration of the investigational medicinal product (IMP) and must have a negative serum pregnancy test at Screening.

Exclusion Criteria:

• Systemic (non biologic) or topical treatment within 21 days prior to first dose administration unless in the opinion of the Investigator the medication will not interfere with the trial procedures or compromise safety.
• Active tuberculosis or history of incompletely treated tuberculosis based on medical history or medical report.
• History of any known primary immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test at Screening, or the subject taking antiretroviral medications as determined by medical history and/or subject's verbal report.
• History of a clinically significant infection (systemic infection or serious skin infection requiring parenteral treatment) within 4 weeks prior to randomization.
• History of a helminth parasitic infection within 6 months prior to the date of informed consent that has not been treated with or has failed to respond to standard of care therapy.
• History of anaphylaxis or severe allergic reaction following any biologic therapy

Contacts and Locations

Locations

Germany

LEO Pharma Investigational Site

Berlin, Germany, 14050

Sponsors and Collaborators

LEO Pharma

Investigators

• Study Director: Medical Expert; LEO Pharma

More Information

• Responsible Party: LEO Pharma
• ClinicalTrials.gov Identifier: NCT04674826
• Other Study ID Numbers: LP0162-1491
• First Posted: December 19, 2020
• Last Update Posted: January 5, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data feasibility requests and research proposals are sent to disclosure@leo-pharma.com. If feasibility to share the data from a trial is granted, the ultimate decision is made by an external to the company board (Patient and Scientific Review Board). Data sharing is further subject to signed data sharing agreement. Data will be available in a closed environment for a specified period on time.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Access Criteria: External researchers with no commercial interest who provide scientifically sound research proposal
• URL: https://leopharmatrials.com/en

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Additional relevant MeSH terms:

Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs