Pharmacokinetic, Safety, Tolerability, Immunogenicity, and Pharmacodynamic Study of SB12 in Healthy Subjects

A Randomised, Double-blind, Three-arm, Parallel Group, Single-dose Study to Compare the Pharmacokinetics, Safety, Tolerability, Immunogenicity, and Pharmacodynamics of Eculizumab (SB12, EU Sourced Soliris®, and US Sourced Soliris®) in Healthy Subjects

This study is to evaluate PK, safety, tolerability, immunogenicity, and PD profiles of SB12, EU sourced Soliris, and US sourced Soliris in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Eculizumab

• Study Type: Interventional
• Enrollment (Actual): 240
• 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: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent
• Have a body weight between 70-95 kg and a body mass index between 20.0-29.9 kg/m²
• Have systolic blood pressure (SBP) ≤ 140 and ≥ 90 mmHg, diastolic blood pressure (DBP) ≤ 95 and ≥ 45 mmHg, and pulse rate ≥ 40 and ≤ 100 beats per minute or assessed as not clinically significant
• Have physical examination and 12-lead ECG results without clinically significant finding at Screening and Day -1 visits
• Non-smoker or smoker whose daily smoking does not exceed 10 cigarettes, 3 cigars, or 3 pipes for at least 30 days prior to Screening visit. Subjects should agree to abstain from smoking while resident at the clinical study site.
• Willing to receive vaccination against N. meningitidis at least 14 days prior to IP administration
• Male subjects must be willing to abstain from sexual intercourse or willing to use a condom in addition to having their female partner use another form of contraception unless their partner is infertile from the time of IP administration until 5 months after IP administration
• Must be willing and able to comply with scheduled visits, treatment plan, clinical laboratory tests, and other study procedures including lifestyle considerations
• Have competence in speaking, writing and comprehending the local language where the study is conducted

Exclusion Criteria:

• Have a history/presence of clinically significant atopic allergy, allergic/hypersensitive reactions, or known or suspected clinically relevant drug hypersensitivity to eculizumab or its excipients
• Contraindication for IP or non-IP to be used in the study
• History of N. meningitidis infection
• Known or suspected hereditary or acquired complement deficiency
• Clinically significant active infection within 28 days before IP administration
• Any systemic or local infection, a known risk for developing sepsis and/or known active inflammatory condition
• Have previously been exposed to eculizumab (Soliris and its biosimilar)
• Previous treatment with a monoclonal antibody or fusion protein within 9 months prior to IP administration and/or have an evidence of immunogenicity from previous exposure to a monoclonal antibody or fusion protein
• Have previously been exposed to an immunosuppressive agent or biological agent (any other than a monoclonal antibody or fusion protein) within 120 days prior to IP administration

• Any of the following abnormal laboratory values at Screening and Day -1 visits:

  1. Serum alanine transaminase and/or aspartate transaminase ≥ 1.5 × ULN
  2. Serum C-reactive protein ≥ 10 mg/L
  3. Serum creatinine > 1.5 × ULN
  4. Whole blood cell count < 3000/mm3, absolute lymphocyte count < 800/mm3, and/or absolute neutrophil count ≤ 1500/mm3
  5. Any other laboratory abnormalities assessed as clinically significant by the Investigator
• Positive test result for hepatitis B surface antigen and/or hepatitis B core antibody, hepatitis C virus antibody, or human immunodeficiency virus at Screening
• Surgery within 90 days prior to IP administration, and/or operation during study period
• Average intake of alcoholic beverages of more than 21 units/week for males and 14 units/week for females
• Drug abuse or a positive urinary drug screening result
• Have any prescription medicine or over-the-counter medicines (except paracetamol) that might have an effect on the objectives of the study, within 14 days prior to IP administration
• Donated >100 mL blood or plasma within 28 days prior to IP administration
• Subject directly involved in the conduct of the clinical study
• Vulnerable subjects
• Pregnant or nursing (lactating) women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SB12; SB12 (proposed eculizumab biosimilar)	Drug: Eculizumab; Eculizumab Injection. 300 mg, single dose
Active Comparator: EU Soliris; EU sourced Soliris (eculizumab)	Drug: Eculizumab; Eculizumab Injection. 300 mg, single dose
Active Comparator: US Soliris; US sourced Soliris (eculizumab)	Drug: Eculizumab; Eculizumab Injection. 300 mg, single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCinf	Area under the concentration-time curve from time zero to infinity	Day 1 to Day 64

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUClast	Area under the concentration-time curve from time zero to the last quantifiable concentration	Day 1 to Day 64
Cmax	Maximum observed serum concentration	Day 1 to Day 64
Tmax	Time to reach Cmax	Day 1 to Day 64
Vz	Volume of distribution during terminal phase	Day 1 to Day 64
λz	Terminal rate constant	Day 1 to Day 64
T1/2	Terminal half-life	Day 1 to Day 64
Clearance	Total body clearance	Day 1 to Day 64
%AUCextrap	Percentage of AUCinf due to extrapolation from time of last measurable concentration (Tlast) to infinity	Day 1 to Day 64
Incidence of Treatment-Emergent Adverse Events	Experience at least 1 treatment-emergent adverse event	Day 1 to Day 64
Incidence of Serious Adverse Events	Experience at least 1 serious adverse event	Day 1 to Day 64
Incidence of ADA	Incidence of anti-drug antibodies	Day 1 to Day 64
Incidence NAb	Incidence neutralising antibodies	Day 1 to Day 64

Collaborators and Investigators

• Sponsor: Samsung Bioepis Co., Ltd.
• Investigators: Principal Investigator: Rainard Fuhr, MD, PAREXEL International GmbH, Early Phase Clinical Unit - Berlin

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2018
• Primary Completion (Actual): March 29, 2019
• Study Completion (Actual): April 8, 2019

Study Registration Dates

• First Submitted: October 24, 2018
• First Submitted That Met QC Criteria: October 25, 2018
• First Posted (Actual): October 26, 2018

Study Record Updates

• Last Update Posted (Actual): January 9, 2020
• Last Update Submitted That Met QC Criteria: January 6, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Eculizumab
• Other Study ID Numbers: SB12-1001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes