Pharmacokinetics/Pharmacodynamics (PK/PD) Equivalence Study of MSB11456

Randomized, Double-Blind, Parallel-Group, Single-Dose Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, Tolerability and Immunogenicity of MSB11456, US-licensed Actemra® and EU-approved RoActemra® in Healthy Adult Subjects

This study aims to compare the PK/PD of a single injection of investigational Medicinal Product (IMP) MSB11456, US licensed Actemra and EU approved RoActemra in healthy adult subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: MSB11456; Drug: US-licensed Actemra; Drug: EU-approved RoActemra

• Study Type: Interventional
• Enrollment (Actual): 696
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand
    • Research Site
  • Christchurch, New Zealand
    • Research Site

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 male and female subjects, 18 to 55 years of age, with a body mass index (BMI) between 18 and 29.9 kilogram per meter square (kg/m^2).
• Subjects who are on adequate contraception as defined in the protocol and are willing and able to comply with the scheduled study visits, Investigational medicinal product (IMP) administration, safety laboratory tests, and all other study procedures.
• Other protocol defined inclusion criteria could apply.

Exclusion Criteria:

• Subjects with history and/or current presence of clinically significant atopic allergy (for example, asthma including childhood asthma, urticaria, angio-edema, eczematous dermatitis).
• Subjects with hypersensitivity or allergic reactions, including known or suspected clinically relevant drug hypersensitivity to any components of the IMP formulations, comparable drugs, or to latex.
• Subjects who have active or latent tuberculosis as indicated by a positive QuantiFERON®-Tuberculosis (TB) Gold test or a history of tuberculosis, lifetime history of invasive systemic fungal infections (for example, histoplasmosis) or other opportunistic infections, including recurrent or chronic local fungal infections, frequent (more than 3 per year requiring treatment) chronic or recurrent infections, having previously been treated with tocilizumab or taken a recombinant monoclonal antibody.
• Subjects who have received a live vaccine within 12 weeks before enrolling in this study or planning for any such vaccination during the study or within 4 months after IMP administration.
• Other protocol defined exclusion criteria could apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MSB11456	Drug: MSB11456; Subjects will receive a single injection of MSB11456 on Day 1.
Active Comparator: US-licensed Actemra	Drug: US-licensed Actemra; Subjects will receive a single injection of US-licensed actemra on Day 1.
Active Comparator: EU-approved RoActemra	Drug: EU-approved RoActemra; Subjects will receive a single injection of EU-approved RoActemra on Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Serum Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of MSB11456, US-licensed Actemra, and EU-approved RoActemra	Up to Day 48
Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of MSB11456, US-licensed Actemra, and EU-approved RoActemra	Up to Day 48
Maximum Observed Serum Concentration (Cmax) of MSB11456, US-licensed Actemra, and EU-approved RoActemra	Up to Day 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Area Under Curve From Tme Zero to 72 Hours After Dosing (AUC 0-72) of MSB11456, US-licensed Actemra, and EU-approved RoActemra	Up to Day 48
Percentage of Area Under Curve From Zero to Infinity (AUC0-∞) Obtained by Extrapolation (AUC extra%) of MSB11456, US-licensed Actemra, and EU-approved RoActemra	Up to Day 48
Time To Reach Maximum Serum Concentration (tmax) of MSB11456, US-licensed Actemra, and EU-approved RoActemra	Up to Day 48
Time to Last Observed Serum Concentration (tlast) of MSB11456, US-licensed Actemra, and EU-approved RoActemra	Up to Day 48
Apparent Terminal Rate Constant (λz) of MSB11456, US-licensed Actemra, and EU-approved RoActemra	Up to Day 48
Apparent Terminal Half-life (t½) of MSB11456, US-licensed Actemra, and EU-approved RoActemra	Up to Day 48
Apparent Total Body Clearance of Drug from Serum Following Subcutaneous Administration (CL/F) of MSB11456, US-licensed Actemra, and EU-approved RoActemra	Up to Day 48
Safety Profile as Assessed by Incidence of Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Injection Site Reactions, Laboratory Variables, Vital Signs and Electrocardiogram (ECG) Measurements	Up to Day 48
Immunogenicity as Assessed by Incidence of Antidrug Antibodies (ADAs), Neutralizing Antibodies (NABs)	Up to Day 48

Collaborators and Investigators

• Sponsor: Fresenius Kabi SwissBioSim GmbH
• Investigators: Study Director: Medical Responsible, Fresenius Kabi SwissBioSim GmbH

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2017
• Primary Completion (Actual): October 1, 2019
• Study Completion (Actual): October 1, 2019

Study Registration Dates

• First Submitted: August 30, 2017
• First Submitted That Met QC Criteria: September 13, 2017
• First Posted (Actual): September 14, 2017

Study Record Updates

• Last Update Posted (Actual): February 12, 2020
• Last Update Submitted That Met QC Criteria: February 10, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: MSB11456; RoActemra®; Actemra®
• Other Study ID Numbers: MS200740-0001

Drug and device information, study documents

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