Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, and Immunogenicity Study of SB16 in Healthy Male Subjects

NCT04621318 | Completed Phase 1 FDA Drug

• 1 other identifier: SB16-1001
• Study Type: interventional
• Target: 168
• Locations: 2 countries
• Sites: 2

Brief Summary

This study is to compare PK, PD, safety, tolerability, and immunogenicity profiles of SB16, EU sourced Prolia, and US sourced Prolia in healthy male subjects.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• AUCinf

  Area under the concentration-time curve from time zero to infinity

  Day 1 to Day 197

• AUClast

  Area under the concentration-time curve from time zero to the last quantifiable concentration

  Day 1 to Day 197

• Cmax

  Maximum serum concentration

  Day 1 to Day 197

Secondary Outcomes (11)

• Tmax

  Day 1 to Day 197

• Vz/F

  Day 1 to Day 197

• λz

  Day 1 to Day 197

• t1/2

  Day 1 to Day 197

• CL/F

  Day 1 to Day 197

Study Arms (3)

SB16

EXPERIMENTAL

SB16 (proposed denosumab biosimilar)

Drug: Denosumab

EU Prolia

ACTIVE COMPARATOR

EU sourced Prolia (denosumab)

Drug: Denosumab

US Prolia

ACTIVE COMPARATOR

US sourced Prolia (denosumab)

Drug: Denosumab

Interventions

Denosumab DRUG

60 mg, single-dose

EU Prolia; SB16; US Prolia

Eligibility Criteria

• Age: 28 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male, aged 28-55 years (inclusive) on the day of signing the informed consent.
• Have a body weight between 60.0-90.0 kg (inclusive) and a BMI between 20.0-29.9 kg/m2 (inclusive).
• Have 12-lead ECG results without clinically significant abnormal findings confirmed by the Investigator.
• Have vital sign results without clinically significant abnormal findings confirmed by the Investigator.
• Have physical examination results without clinically significant abnormal findings confirmed by the Investigator.
• Male subjects who have not had surgical sterilisation 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, such as an intra-uterine device, oral contraceptive, injectable progesterone, sub-dermal implant, or tubal ligation unless their partners are infertile (confirmed with written verifications) during the treatment period.
• Willing and able to comply with scheduled visits, treatment plan, clinical laboratory tests, and other study procedures including lifestyle considerations.
• Able to provide written informed consent, which must be obtained prior to any study related procedures being performed.
• Have competence in speaking, writing, and comprehending the local language(s) where the study is conducted.

You may not qualify if:

• Have a history and/or current presence of clinically significant atopic allergy, hypersensitivity, or allergic reactions (either spontaneous or following drug administration), also including known or suspected clinically relevant drug hypersensitivity to denosumab or to any of the excipients.
• Have a history of and/or current clinically significant gastrointestinal, renal, hepatic, cardiovascular, haematological, pulmonary, neurologic, metabolic, psychiatric disorder, drug or alcohol abuse, or allergic disease excluding mild asymptomatic seasonal allergies.
• Have a history of bone disease or any medical condition that can affect bone metabolism (including osteoporosis, osteogenesis imperfecta, osteomalacia, hyperparathyroidism, hyperthyroidism, hypothyroidism, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Paget's disease of the bone, and malabsorption syndrome).
• Have a history of malignancy (including lymphoma, leukaemia, and skin cancer).
• Have ONJ or risk factors for ONJ such as invasive dental procedures or active periodontal disease within 180 days prior to Randomisation.
• Have bone fractures within 180 days prior to Randomisation.
• Have a history of serious infection (associated with hospitalisation and/or which required intravenous antibiotics) within 180 days prior to Randomisation.
• Have a clinically significant active infection (bacterial, viral, or fungal) including skin infections within 28 days prior to Randomisation.
• Have any systemic or local infection, a known risk for developing sepsis.
• Have known intolerance to calcium or vitamin D supplements.
• Have previously been exposed to denosumab (Prolia®/Xgeva®) and its biosimilar.
• Have previously been exposed to a monoclonal antibody or fusion protein within 270 days (other than denosumab) prior to Randomisation and/or there is confirmed evidence or clinical suspicion 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 Randomisation.
• Have received live vaccines(s) within 30 days prior to Randomisation or who will require live vaccine(s) during the study period.
• Have a personal or family history of prolonged QT interval syndrome or Torsade de Pointes, or family history of sudden death.

Sponsors & Collaborators

• Samsung Bioepis Co., Ltd.: lead

Study Sites (2)

Biotrial

Newark, New Jersey, 07103, United States

Location

Biotrial Rennes

Rennes, France

Location

Related Publications (1)

• Lee HA, Kim S, Seo H, Kim S. A phase I, randomized, double-blind, single-dose pharmacokinetic study to evaluate the biosimilarity of SB16 (proposed denosumab biosimilar) with reference denosumab in healthy male subjects. Expert Opin Investig Drugs. 2023 Jul-Dec;32(10):959-966. doi: 10.1080/13543784.2023.2273510. Epub 2023 Nov 6.

  PMID: 37870163 DERIVED

MeSH Terms

Interventions

Denosumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Hakim Charfi, MD

  Biotrial Rennes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2020
• First Posted: November 9, 2020
• Study Start: October 19, 2020
• Primary Completion: November 9, 2022
• Study Completion: November 9, 2022
• Last Updated: November 28, 2022

Record last verified: 2022-11

Locations

FR (1); US (1)