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

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

Study Overview

• Status: Completed
• Conditions: Osteoporosis, Osteopenia
• Intervention / Treatment: Drug: SHR-1222; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410011
      • The second Xiangya Hospital of Central South University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 59 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Second Xiangya Hospital of Central South University
• Investigators: Principal Investigator: Zhiguang Zhou, MD, Second Xiangya Hospital of Central South University

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2019
• Primary Completion (Actual): July 27, 2020
• Study Completion (Actual): August 15, 2020

Study Registration Dates

• First Submitted: March 26, 2019
• First Submitted That Met QC Criteria: March 28, 2019
• First Posted (Actual): April 1, 2019

Study Record Updates

• Last Update Posted (Actual): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 29, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Osteoporosis; Bone Diseases, Metabolic
• Other Study ID Numbers: 2019 SHR-1222

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