Effects of SHR-1222 on Vascular Inflammatory Factors in Patients With Low Bone Mass

Study Overview
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Brief Summary
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This study aims to investigate the effects of SHR-1222 on vascular inflammatory factors in patients with low bone mass.

Detailed Description
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In this study, total 50 patients with low bone mass will be enrolled and divided into 5 dose groups. In the lowest dose group 6 subjects will be recruited, among whom 4 will receive SHR-1222 and the other 2 will receive placebo. In each of the other 4 groups, 11 subjects will be recruited, among whom 9 will be administered with SHR-1222 and the other 2 with placebo. Levels of nitric oxide (NO), Endothelin-1 (ET-1), plasminogen activator inhibitor-1 (PAI-1) and hypersensitivity C-reactive protein (hs-CRP) will be detected in patients before and after the SHR-1222 injection.

Official Title
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Effects of SHR-1222 on Vascular Inflammatory Factors in Patients With Low Bone Mass

Conditions
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Osteoporosis, Osteopenia

Intervention / Treatment
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* Drug: SHR-1222
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent; Male or postmenopausal female; Age ≥45 and ≤59 years old; The body mass index (BMI) ≥18.5kg/m2 and ≤28 kg/m2; T value of areal bone mineral density on any lumbar spine (L1-L4) or collum femoris>-2.5 and <-1; The comprehensive physical examination is eligible or slightly abnormal but the researchers determine no clinical implication; No smoking, alcohol or drugs abuse. Exclusion Criteria: Any disease affecting bone metabolism; Past medical history of cerebral infarction or cerebral arterial thrombosis; Past medical history of myocardial infarction; Administration of the following drugs within 6m: Hormone replacement therapy, Calcitonin Parathyroid hormone (or any derivative), Supplemental Vitamin D>1,000 IU/day, Glucocorticosteroids (inhaled or topical corticosteroids administered more than 2 weeks before the enrollment date are allowed), Anabolic steroids, Calcitriol and available analogues, thiazide diuretics; Administration of the following drugs within 12m: Bisphosphonates, Fluoride for osteoporosis; A bone fracture within the previous 6 months; A lumbar spine L1-L4 or femoral neck T-score ≤-2.5; Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or gamma pancreatic acyl transferase (GGT) or total bilirubin, more than 1.5 x ULN during screening; 3 months prior to screening involved in any drug clinical subjects; Subjects determined by the researchers have any food, dietary supplement or drugs that affect SHR-1222 absorption, distribution, metabolism and excretion in 4 weeks prior to screening or within 5 half-lives; Serious infection, trauma or major surgery in 4 weeks prior to screening; A surgery plan during the study; Blood donation and transfusion in 3 months prior to screening; Unstable thyroid dysfunction in 6 months prior to screening; Human immunodeficiency virus antibody (HIV-ab), syphilis serological examination, hepatitis b virus surface antigen (HBsAg), hepatitis c virus antibody (HCV-ab) were positive; Intolerant to venous blood collection; A clinical history of drug allergy or a history of atopic allergic diseases (asthma, urticaria, eczema dermatitis) or a known allergy to experimental or similar； Subjects with any other situation should not be involved, which determined by the researchers.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>A single subcutaneous injection of SHR-1222 dose 1 versus placebo | Drug: SHR-1222<br>* Pharmaceutical form: water injection; Route of administration: subcutaneous<br>Drug: Placebo<br>* Pharmaceutical form: water injection; Route of administration: subcutaneous<br>|
| Experimental: Cohort 2<br>A single subcutaneous injection of SHR-1222 dose 2 versus placebo | Drug: SHR-1222<br>* Pharmaceutical form: water injection; Route of administration: subcutaneous<br>Drug: Placebo<br>* Pharmaceutical form: water injection; Route of administration: subcutaneous<br>|
| Experimental: Cohort 3<br>A single subcutaneous injection of SHR-1222 dose 3 versus placebo | Drug: SHR-1222<br>* Pharmaceutical form: water injection; Route of administration: subcutaneous<br>Drug: Placebo<br>* Pharmaceutical form: water injection; Route of administration: subcutaneous<br>|
| Experimental: Cohort 4<br>A single subcutaneous injection of SHR-1222 dose 4 versus placebo | Drug: SHR-1222<br>* Pharmaceutical form: water injection; Route of administration: subcutaneous<br>Drug: Placebo<br>* Pharmaceutical form: water injection; Route of administration: subcutaneous<br>|
| Experimental: Cohort 5<br>A single subcutaneous injection of SHR-1222 dose 5 versus placebo | Drug: SHR-1222<br>* Pharmaceutical form: water injection; Route of administration: subcutaneous<br>Drug: Placebo<br>* Pharmaceutical form: water injection; Route of administration: subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of serum nitric oxide (NO) change after the administration of SHR-1222 | NO level will be detected by nitrite/nitrate assay (colorimetric). | Day0 before the administration and Day 2, 4, 7, 15, 29, 43, 57 after the administration | 
| Assessment of serum Endothelin-1 (ET-1) change after the administration of SHR-1222 | ET-1 level will be detected by ELISA. | Day0 before the administration and Day 2, 4, 7, 15, 29, 43, 57 after the administration | 
| Assessment of serum plasminogen activator inhibitor-1 (PAI-1) change after the administration of SHR-1222 | PAI-1 level will be detected by ELISA. | Day0 before the administration and Day 2, 4, 7, 15, 29, 43, 57 after the administration | 
| Assessment of serum hypersensitivity C-reactive protein (hs-CRP) change after the administration of SHR-1222 | hs-CRP level will be detected by immunoturbidimetry assay. | Day0 before the administration and Day 2, 4, 7, 15, 29, 43, 57 after the administration |