A Pharmacokinetic Similarity Study in Healthy Male Subjects to Evaluate Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of LY06006 Versus US-Prolia and EU-Prolia by Single-dose Subcutaneous Injection

NCT06095427 | Completed Phase 1 FDA Drug

• 3 other identifiers: LY06006/CT-EUR-1012472282020-000286-16
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 2

Brief Summary

This trial is a randomized, double-blind, three-arm, parallel-group, pharmacokinetic study. The purpose of this study is to demonstrate pharmacokinetic (PK) similarity and to compare safety, immunogenicity and pharmacodynamics (PD) between the test product L06006 and the reference products US-Prolia and EU-Prolia in healthy male subjects. A total of 300 healthy male subjects aged 28 to 65 years (both inclusive) will be randomized 1:1:1 to receive a single subcutaneous (s.c.) injection of either LY06006 or US-Prolia or EU-Prolia on Day 1 and then be followed for 36 weeks.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• AUC0-t

  Area under the concentration-time curve (AUC) from time zero to last quantifiable concentration (AUC0-t)

  Day 1 until Day 253

• Cmax

  Maximum serum concentration (Cmax)

  Day 1 until Day 253

• AUC0-inf

  Area under the concentration-time curve (AUC) from time zero to infinity (AUC0-inf) AUC0-inf = AUC from time zero to the last quantifiable concentration (AUC0-t) + last observed concentration (Ct) / terminal rate constant (λz)

  Day 1 until Day 253

Secondary Outcomes (18)

• tmax

  Day 1 until Day 253

• t½

  Day 1 until Day 253

• CL/F

  Day 1 until Day 253

• Vd

  Day 1 until Day 253

• λz

  Day 1 until Day 253

Study Arms (3)

LY06006

EXPERIMENTAL

60 mg LY006006

Biological: LY06006 (Denosumab Biosimilar)

US-Prolia

ACTIVE COMPARATOR

60 mg US-Prolia

Biological: US-Prolia (Denosumab)

EU-Prolia

ACTIVE COMPARATOR

60 mg EU-Prolia

Biological: EU-Prolia

Interventions

LY06006 (Denosumab Biosimilar) BIOLOGICAL

single dose of 60 mg LY006006 s.c.

LY06006

US-Prolia (Denosumab) BIOLOGICAL

single dose of 60 mg US-Prolia s.c.

US-Prolia

EU-Prolia BIOLOGICAL

single dose of 60 mg EU-Prolia s.c.

EU-Prolia

Eligibility Criteria

• Age: 28 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy males aged 28 - 65 years, both inclusive;
• Body mass index (BMI) between 18 to \< 30 kg/m2 and body weight of 60 - 90 kg (both inclusive);
• Subjects must give written informed consent before any assessment is performed and has to understand the study and must be willing to follow and complete all the test procedures;
• Clinically acceptable physical exams and laboratory tests (blood hematology, blood chemistry, coagulation, urinalysis) and no history or evidence of any clinically significant medical disorder that would pose a risk to subject safety or interfere with study evaluations or procedures;
• Available for long term clinical assessments (36 weeks post-dose) for PK/PD and immunogenicity assessments;
• Subjects and their female partners who are of childbearing potential must be using 2 forms of birth control (1 of which is a highly effective method† and 1 must be a barrier method‡) or abstain from sexual intercourse with a female partner (acceptable only if it is the subject's usual form of birth control/lifestyle choice) starting at Day -1 and throughout the study period and for at least 1 month after the end of EoS Visit. A condom is required to be used also by vasectomized men to prevent delivery of the drug via seminal fluid.
• Highly effective forms of birth control include (i.e., less than 1% failure rate per year when used consistently and correctly):
• hormonal contraception, i.e., oral, injectable or implantable hormonal contraceptives for the female partner (Note: Not all oral contraception methods have a low failure rate.).
• hormonal or non-hormonal intrauterine device (IUD), established IUD (loop) or intrauterine system for the female partner.
• the subject has undergone effective surgical sterilization before he entered the study.
• the subject's female partner has undergone effective surgical sterilization before the subject entered the clinical trial and she is the sole sexual partner of the subject during the study.
• Acceptable methods of surgical sterilization are:
• Surgical bilateral oophorectomy for the female partner (with or without hysterectomy) at least 6 weeks before the SCR Visit.
• Hysterectomy for the female partner at least 6 weeks before the SCR Visit.
• Bilateral tubal ligation for the female partner at least 6 weeks before the SCR Visit.

You may not qualify if:

• Subjects with prior exposure to denosumab (Prolia, Xgeva, or biosimilar denosumab);
• Use of any other monoclonal antibodies or fusion proteins within the 3 months or 5 half-lives (whatever is longer) before the date of administration of the IMP;
• Subjects being on a special diet or with significant weight loss from a weight reduction diet (e.g., more than approx. 5 kg within 1 month) before the SCR Visit or unwilling to maintain the same weight for the duration of the study;
• Donation or loss of ≥ 500 mL of blood within 8 weeks prior to dosing, or longer if required by local regulation. Plasma donation within 28 days prior to dosing;
• Diseases and conditions that affect bone metabolism e.g., osteoporosis, hypo/hyper-parathyroidism (excluding isolated deviations of parathormone assessed as not clinically significant); hypo-/hyperthyroidism, Cushing's syndrome, malabsorption syndromes, rheumatoid arthritis, psoriatic arthritis, osteomalacia, bone fractures within 6 months, or any contraindications to denosumab therapy;
• Vitamin D deficiency (serum 25-hydroxy vitamin D \< 20 ng/mL). For subjects with vitamin D deficiency, a single attempt at oral replenishment with re-evaluation prior to randomization is permitted (see Section 5.5);
• Subjects with systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg and / or pulse \< 50 or \> 90 bpm (mean of triplicate measurements. Subjects with pulse rate between 45 and 50 bpm (inclusive) may be enrolled provided they have a normal thyroid function, no clinical symptoms associated with the bradycardia and no apparent signs of other diseases causing bradycardia (e.g., cardiovascular disease);
• Subjects with abnormal ECGs (QTcF \> 450 ms, signs of ischemia, sinus tachycardia \[heart rate, HR \> 90\] or sinus bradycardia \[HR \< 50\], ventricular conduct delay \[QRS \> 120 ms\] or others) which, in the judgment of the Investigator or any of the Sub-Investigators, may be clinically relevant. Subjects with heart rate between 45 and 50 bpm (inclusive) may be enrolled provided they have a normal thyroid function, no clinical symptoms associated with the bradycardia and no apparent signs of other diseases causing bradycardia (e.g., cardiovascular disease). Potential cardiovascular disease resulting in bradycardia should be excluded by further investigations on the discretion of the Investigator;
• Subject presents with any psychiatric disorder, which may prevent the subject from completing the study or interfere with the interpretation of the study results;
• Subjects with current or a history of clinically significant (or "serious") skin infections or skin disorders;
• Subject has a history or presence of anemia or coagulopathy;
• Significant changes in physical activity during the 6 months before IMP administration or constant levels of intense physical exercise;
• Positive test results for hepatitis B surface antigen (HbsAg), anti-hepatitis B core (anti-HBc) antibodies indicative of active hepatitis, optionally Hepatitis B surface antibody (anti-HBS), hepatitis A virus antibodies (immunoglobulin M \[IgM\]), hepatitis C virus (HCV) antibodies and / or human immunodeficiency virus (HIV) type-1 and / or type-2 antibodies at the SCR Visit;
• Use of any prescription drug or any over-the-counter (OTC) drug within the 2 weeks (or less than 5 x the half-life of that medication, whichever is longer) including herbal supplements, or prescribed/ non-prescribed marijuana derivatives before the date of administration of the IMP (excluding localized use not intended to have systemic action and occasional use of paracetamol of up to 2 g per day), which, in the judgment of the Investigator or Sub-Investigators, may affect participation in this clinical study. Vitamins, minerals and nutritional supplements may be taken at the discretion of the Investigator;
• Prior use of any medications that may affect bone turnover within 12 months of IMP administration and for the duration of the study. This includes medications such as, but not limited to: bisphosphonates, fluoride, or selective estrogen receptor modulator, such as ralaxofene, calcitonin, strontium, parathyroid hormone or derivatives, supplemental vitamin D \[\> 1000 IU/day\], except for the potential vitamin D replenishment after SCR, glucocorticosteroids, anabolic steroids, calcitriol, diuretics. Current use of anti-angiogenic drugs;

Sponsors & Collaborators

• Luye Pharma Group Ltd.: lead
• Parexel: collaborator

Study Sites (2)

Parexel International GmbH, Early Phase Clinical Unit Berlin

Berlin, 14050, Germany

Location

CTC North GmbH & Co KG

Hamburg, 20251, Germany

Location

Related Publications (1)

• Fuhr R, Sun X, Wang X, Dong Y, Tai J, Zhou M, Dou C. A three-arm clinical study to compare pharmacokinetic and pharmacodynamic similarity of the denosumab biosimilar LY06006 with reference denosumab in healthy male subjects. Expert Opin Drug Metab Toxicol. 2024 Nov 24:1-9. doi: 10.1080/17425255.2024.2432673. Online ahead of print.

  PMID: 39582128 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

• R Fuhr, MD

  Parexel

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: This is a multi-center, randomized, double-blind, single-dose, three-arm, parallel-group study designed to demonstrate the PK similarity between LY06006, US-Prolia and EU-Prolia and to evaluate the safety, tolerability, immunogenicity and PD of LY06006 compared with US-Prolia and EU-Prolia.

Study Record Dates

• First Submitted: May 5, 2023
• First Posted: October 23, 2023
• Study Start: March 9, 2021
• Primary Completion: March 14, 2023
• Study Completion: March 14, 2023
• Last Updated: October 23, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)