A Study to Evaluate LY06006 and Prolia in Healthy Adults

A Randomized, Double-blind, Parallel-group Study in Chinese Healthy Male Subjects to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of LY06006 Versus Prolia Following Single-dose Subcutaneous Injection

A randomized, double-blind, parallel-group study in Chinese healthy male subjects to evaluate the pharmacokinetics, pharmacodynamics, safety and immunogenicity of LY06006 versus Prolia following single-dose subcutaneous injection

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy Adults
• Intervention / Treatment: Drug: LY06006; Drug: Prolia

Detailed Description

Study Design:

The study is a randomized, double-blind, parallel-group study in healthy adult male subjects to evaluate the pharmacokinetics, pharmacodynamics, safety and immunogenicity of LY06006 versus Prolia following single-dose subcutaneous injection.

A total of 168 healthy male subjects will be randomized 1:1 to receive a single subcutaneous (s.c.) injection of 60mg of either LY06006 ( LY06006 , 60 mg/1mL , Shandong Luye Pharmaceutical Co., Ltd.) or Prolia (60 mg / 1 mL , Amgen Inc.). During the entire study period, blood samples should be collected according to the Schedule of Assessments for pharmacokinetic, pharmacodynamic and immunogenicity analysis, and safety assessments should be conducted.

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410013
      • The Third Xiangya Hospital of Central South University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Voluntarily signed the informed consent form;
2. Healthy males，ages ≥18 to ≤50 years;
3. Body weight ≥58 to ≤68 kg and Body mass index (BMI) >18 to <28 kg/m2, body mass index (BMI) = weight ( kg ) / height 2 (m 2);
4. Normal or clinically acceptable vital signs, physical exams, laboratory tests, 12- lead ECG, abdominal color Doppler ultrasound, chest radiograph, etc. screening;
5. No pregnancy plans and voluntarily take effective contraceptive measures from the screening date to the end of the study .

Exclusion Criteria:

1. Prior diagnosis of bone disease, or any condition that will affect bone metabolism such as, but not limit to: malignant tumors ( including myeloma ), hypoparathyroidism / hyperthyroidism, hypothyroidism / hyperthyroidism, acromegaly, Cushing ' s syndrome, hypopituitarism, severe chronic obstructive pulmonary disease, rheumatoid arthritis, osteomalacia;
2. Prior history or current evidence of osteomyelitis or osteonecrosis of the jaw (ONJ), or risk factors for ONJ such as invasive dental surgery or jaw surgery during the trial, or unhealed dental or oral surgery wounds;
3. Recent bone fracture within 6 months;
4. Active and unhealed infections of the respiratory system, digestive system, urinary system, reproductive system, or skin;
5. Serum calcium of < Lower Limit of Normal (LLN) or > Upper Limit of Normal (ULN);
6. Prior use of medications affecting bone turnover before screening and for the duration of study, including but not limited to: denosumab, bisphosphonates or fluoride within 12 months, contraceptives containing estrogen, tibolone, estrogen, selective estrogen receptor modulators, aromatase inhibitors, calcitonin, strontium salts, parathyroid hormone (or derivatives), vitamin D supplements ( >1000 IU/ day), anabolic steroids, systemic glucocorticoids, calcitriol or similar, diuretics, anticonvulsants within 6 months; inhaled or topical glucocorticoid drugs within 2 weeks;
7. Allergy to more than two drugs or food, or allergy to the ingredients of the investigational medicinal product (IMP);
8. Blood donation or massive blood loss ( ≥200 mL ) within 3 months before screening ;
9. Any vaccination within 6 months before screening or for the duration of study;
10. Prior use of any prescription drugs, over-the-counter drugs, any vitamin products or herbal medicines within 14 days before screening ;
11. Intense physical exercise within 2 weeks before screening or for the duration of the study, or any other conditions affecting drug absorption, distribution, metabolism, and excretion;
12. Upon enquiry, prior smoke more than 5 cigarettes per day within 3 months before the study;
13. Upon enquiry, a history of alcohol abuse ( drinking more than 14 units of alcohol per week within the first three months prior to screening : 1 unit = 350 mL of beer, 45 mL of liquor, or 150 mL of wine ), or positive alcohol test;
14. Positive urine screen for drug or a history of drug abuse or drug use in the past five years upon questioning ;
15. Other diseases with clinical significance (such as nervous system, mental system , cardiovascular system, urinary system, digestive system, respiratory system, metabolic endocrine system, blood system, skin disease, immune disease, tumor, etc.);
16. Any of the following tests positive: hepatitis B surface antigen ( HBsAg ), hepatitis C antibody ( HCV-AB ), human immunodeficiency virus antigen antibody ( HIVAg / Ab ) and treponema pallidum antibody;
17. Acute diseases or concomitant medications from screening to IMP administration;
18. Consumption of any alcohol-containing products within 48 hours before administration of the IMP ;
19. Prior participation in clinical trials for denosumab or denosumab biosimilar products; current participation in other clinical studies, or receiving or have received any investigational drug within 3 months (or less than 5-half lives of that medication, whichever time period is longer) before receiving study drug ;
20. History of fainting blood or needles;
21. In the opinion of the investigator, others to be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LY06006; 60 mg/1 ml, once every 6 months administered subcutaneously	Drug: LY06006; 60 mg/1 ml, once every 6 months administered subcutaneously; Other Names: subcutaneous injection of 60 mg
ACTIVE_COMPARATOR: Prolia; 60 mg/1 ml, once every 6 months administered subcutaneously	Drug: Prolia; 60 mg/1 ml, once every 6 months administered subcutaneously; Other Names: Denosumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC 0- ∞	Area under the concentration-time curve from time zero to infinity	168 days
C max	Maximum observed concentration	168 days
s-CTX	Percent change in serum s-CTX from baseline.	168 days
AUEC0-t	The pharmacodynamic parameters	168 days
Emax	The pharmacodynamic parameters	168 days
TEmax	The pharmacodynamic parameters	168 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vital signs：Temperature	Safety measures	168 days
Vital signs：pulse	Safety measures	168 days
Vital signs： blood pressure	Safety measures	168 days
Vital signs： respiration	Safety measures	168 days
Physical examination：general	Safety measures	168 days
Physical examination：head and neck region	Safety measures	168 days
Physical examination：lymph gland	Safety measures	168 days
Physical examination： oral cavity	Safety measures	168 days
Physical examination：chest	Safety measures	168 days
Physical examination：belly	Safety measures	168 days
Physical examination：Extremities and spine	Safety measures	168 days
Physical examination：nervous system	Safety measures	168 days
Laboratory tests：hematology	Safety measures	168 days
Laboratory tests：chemistry	Safety measures	168 days
Laboratory tests：urinalysis	Safety measures	168 days
Laboratory tests：parathyroid hormone	Safety measures	168 days
Laboratory tests：thyroid function	Safety measures	168 days
Laboratory tests：abdomen ultrasound	Safety measures	168 days
Laboratory tests：chest radiography	Safety measures	168 days
Laboratory tests：coagulation function	Safety measures	168 days
Electrocardiogram (12-Lead ECG)	Safety measures	168 days
Adverse events(AEs)	Safety measures	168 days
ADA	The incidence and antibody titer of ADA	168 days
Nab	The incidence of Nab.	168 days

Collaborators and Investigators

• Sponsor: Luye Pharma Group Ltd.
• Collaborators: Shan Dong Boan Biotechnology Co., Ltd
• Investigators: Principal Investigator: Guoping Yang, doctor, The Third Xiangya Hospital of Central South University

Publications and helpful links

General Publications

• Wang S, Yang X, Huang J, Yang S, Wu Q, Chen H, Wu S, Dou C, Yang G, Xiang Y. Pharmacokinetics, pharmacodynamics, safety, and immunogenicity of a biosimilar of denosumab (LY06006): a randomized, double-blind, single-dose, parallel-controlled clinical study in healthy Chinese subjects. Expert Opin Investig Drugs. 2022 Oct;31(10):1133-1142. doi: 10.1080/13543784.2022.2120389. Epub 2022 Sep 7.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 9, 2020
• Primary Completion (ACTUAL): April 10, 2021
• Study Completion (ANTICIPATED): December 31, 2021

Study Registration Dates

• First Submitted: April 20, 2021
• First Submitted That Met QC Criteria: July 13, 2021
• First Posted (ACTUAL): July 22, 2021

Study Record Updates

• Last Update Posted (ACTUAL): July 22, 2021
• Last Update Submitted That Met QC Criteria: July 13, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Immunogenicity; Pharmacodynamics; Healthy Adults; Prolia; Compare; LY06006
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: LY06006/CT-CHN-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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