Clinical trial NCT04973722: A Study to Evaluate LY06006 and Prolia in Healthy Adults
Official title: 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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Healthy Adults
Keywords: Compare
Pharmacokinetics
Pharmacodynamics
Safety
Immunogenicity
LY06006
Prolia
Healthy Adults
Lead sponsor: Luye Pharma Group Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Shan Dong Boan Biotechnology Co., Ltd
First posted: 2021-07-22
Enrollment: 168
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: AUC 0- ∞
timeFrame: 168 days
measure: C max
timeFrame: 168 days
measure: s-CTX
timeFrame: 168 days
measure: AUEC0-t
timeFrame: 168 days
measure: Emax
timeFrame: 168 days
measure: TEmax
timeFrame: 168 days
Secondary outcomes:
measure: Vital signs：Temperature
timeFrame: 168 days
measure: Vital signs：pulse
timeFrame: 168 days
measure: Vital signs： blood pressure
timeFrame: 168 days
measure: Vital signs： respiration
timeFrame: 168 days
measure: Physical examination：general
timeFrame: 168 days
measure: Physical examination：head and neck region
timeFrame: 168 days
measure: Physical examination：lymph gland
timeFrame: 168 days
measure: Physical examination： oral cavity
timeFrame: 168 days
measure: Physical examination：chest
timeFrame: 168 days
measure: Physical examination：belly
timeFrame: 168 days
measure: Physical examination：Extremities and spine
timeFrame: 168 days
measure: Physical examination：nervous system
timeFrame: 168 days
measure: Laboratory tests：hematology
timeFrame: 168 days
measure: Laboratory tests：chemistry
timeFrame: 168 days
measure: Laboratory tests：urinalysis
timeFrame: 168 days
measure: Laboratory tests：parathyroid hormone
timeFrame: 168 days
measure: Laboratory tests：thyroid function
timeFrame: 168 days
measure: Laboratory tests：abdomen ultrasound
timeFrame: 168 days
measure: Laboratory tests：chest radiography
timeFrame: 168 days
measure: Laboratory tests：coagulation function
timeFrame: 168 days
measure: Electrocardiogram (12-Lead ECG)
timeFrame: 168 days
measure: Adverse events(AEs)
timeFrame: 168 days
measure: ADA
timeFrame: 168 days
measure: Nab
timeFrame: 168 days
Other outcomes:
Locations:
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
Study officials:
affiliation: The Third Xiangya Hospital of Central South University
name: Guoping Yang, doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.