A Study to Evaluate LY06006 and Prolia in Healthy Adults

Phase 1

• Conditions: Healthy Adults
• Interventions: Drug: Prolia; Drug: LY06006

• Registration Number: NCT04973722
• Lead Sponsor: Luye Pharma Group Ltd.

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.

Study Timeline

• Study Start: 2020-12-09
• Primary Completion: 2021-04-10
• Study First Submitted: 2021-04-20
• Status Verified: 2021-07
• Study First Submitted QC: 2021-07-13
• Last Update Submitted: 2021-07-13
• Study First Posted: 2021-07-22
• Last Update Posted: 2021-07-22
• Study Completion: 2021-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 168

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prolia	Prolia	60 mg/1 ml, once every 6 months administered subcutaneously
LY06006	LY06006	60 mg/1 ml, once every 6 months administered subcutaneously

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

The Third Xiangya Hospital of Central South University; 🇨🇳 Changsha, Hunan, China