The PK/PD Study of A Single Subcutaneous Injection of SHR-1222 in Healthy Subjects

NCT ID: NCT03870100

Last Updated: 2020-06-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-15
• Study Completion Date: 2020-01-06

Brief Summary

This is a Single Center, Randomized, Double-Blind, Dose Escalation, Placebo Parallel Controlled PhaseⅠClinical study to Evaluate the Safety, Tolerability and Pharmacokinetics, Pharmacodynamics with A Single Subcutaneous Injection of SHR-1222 in Healthy Subjects.

The primary objective of this study is to investigate the safety and tolerability of a range of subcutaneous SHR-1222 in healthy subjects. Secondary objectives are to determine the pharmacokinetics (PK) and pharmacodynamics(PD) profile of SHR-1222 in healthy subjects including assessment of immunogenicity.

Detailed Description

50 adult healthy subjects with 5 dose groups will be enrolled in the study, including six subjects in the lowest dose group, four of whom received the SHR-1209 and two of whom received the placebo. The other three groups have 11 subjects in each group, 9 administered SHR-1222 and 2 administered placebo. The primary endpoint is the Safety and Tolerability : adverse events, vital signs, physical examination, laboratory examination, 12 lead electrocardiogram, injection site reactions, etc.

Conditions

Osteoporosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Cohort 1

A single subcutaneous injection of SHR-1222 dose 1 versus placebo

Group Type: EXPERIMENTAL

SHR-1222

Intervention Type: DRUG

Pharmaceutical form: water injection Route of administration: subcutaneous

Placebo

Intervention Type: DRUG

Pharmaceutical form: water injection Route of administration: subcutaneous

Cohort 2

A single subcutaneous injection of SHR-1222 dose 2 versus placebo

Group Type: EXPERIMENTAL

SHR-1222

Intervention Type: DRUG

Pharmaceutical form: water injection Route of administration: subcutaneous

Placebo

Intervention Type: DRUG

Pharmaceutical form: water injection Route of administration: subcutaneous

Cohort 3

A single subcutaneous injection of SHR-1222 dose 3 versus placebo

Group Type: EXPERIMENTAL

SHR-1222

Intervention Type: DRUG

Pharmaceutical form: water injection Route of administration: subcutaneous

Placebo

Intervention Type: DRUG

Pharmaceutical form: water injection Route of administration: subcutaneous

Cohort 4

A single subcutaneous injection of SHR-1222 dose 4 versus placebo

Group Type: EXPERIMENTAL

SHR-1222

Intervention Type: DRUG

Pharmaceutical form: water injection Route of administration: subcutaneous

Placebo

Intervention Type: DRUG

Pharmaceutical form: water injection Route of administration: subcutaneous

Cohort 5

A single subcutaneous injection of SHR-1222 dose 5 versus placebo

Group Type: EXPERIMENTAL

SHR-1222

Intervention Type: DRUG

Pharmaceutical form: water injection Route of administration: subcutaneous

Placebo

Intervention Type: DRUG

Pharmaceutical form: water injection Route of administration: subcutaneous

Interventions

SHR-1222

Pharmaceutical form: water injection Route of administration: subcutaneous

Intervention Type: DRUG

Placebo

Pharmaceutical form: water injection Route of administration: subcutaneous

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Jiangsu HengRui Medicine Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zhiguang Zhou, MD

Role: PRINCIPAL_INVESTIGATOR

2nd Xiangya Hospital of Central South University

Locations

2nd Xiangya Hospital of Central South University

Changsha, , China

Countries

China

References

Dai Z, Fang P, Yan X, Zhu R, Feng Q, Yan Q, Yang L, Fan X, Xie Y, Zhuang L, Feng S, Liu Y, Zhong S, Yang Z, Sheng Z, Zhou Z. Single Dose of SHR-1222, a Sclerostin Monoclonal Antibody, in Healthy Men and Postmenopausal Women With Low Bone Mass: A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation, Phase I Study. Front Pharmacol. 2021 Oct 20;12:770073. doi: 10.3389/fphar.2021.770073. eCollection 2021.

Reference Type: DERIVED

PMID: 34744750 (View on PubMed)

Other Identifiers

SHR-1222-101

Identifier Type: -

Identifier Source: org_study_id