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

• ClinicalTrials.gov Identifier: NCT03722329
• Recruitment Status: Completed
• First Posted: October 26, 2018
• Last Update Posted: January 9, 2020
• Sponsor: Samsung Bioepis Co., Ltd.
• Information provided by (Responsible Party): Samsung Bioepis Co., Ltd.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Eculizumab	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: 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
• Actual Study Start Date: November 13, 2018
• Actual Primary Completion Date: March 29, 2019
• Actual Study Completion Date: April 8, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. AUCinf [ Time Frame: Day 1 to Day 64 ]
   Area under the concentration-time curve from time zero to infinity

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Germany

PAREXEL International GmbH, Early Phase Clinical Unit - Berlin

Berlin, Germany, 14050

Sponsors and Collaborators

Samsung Bioepis Co., Ltd.

Investigators

• Principal Investigator: Rainard Fuhr, MD; PAREXEL International GmbH, Early Phase Clinical Unit - Berlin

More Information

• Responsible Party: Samsung Bioepis Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03722329
• Other Study ID Numbers: SB12-1001
• First Posted: October 26, 2018
• Last Update Posted: January 9, 2020
• Last Verified: January 2020

• 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

Additional relevant MeSH terms:

Eculizumab; Complement Inactivating Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs