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

NCT03870100 | Completed Phase 1

• 1 other identifier: SHR-1222-101
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteoporosis

Outcome Measures

Primary Outcomes (1)

• Number & proportion of subjects with adverse events [Time Frame: dose administration to 85 days after dose administration] Safety and Tolerance: Number & proportion of subjects with adverse events

  Dose administration to 85 days after dose administration

Secondary Outcomes (12)

• Assessment of PK parameter-time to maximum concentration (Tmax)

  Pre-dose to 85 days after dose administration

• Assessment of PK parameter-maximum concentration (Cmax)

  Pre-dose to 85 days after dose administration

• Assessment of PK parameter-area under curve (AUC)

  Pre-dose to 85 days after dose administration

• Assessment of PD parameter-change in serum C-telopeptide (sCTx) from baseline

  Pre-dose to 85 days after dose administration

• Assessment of PD parameter-change in aminoterminal propeptide type-1 procollagen (P1NP) from baseline

  Pre-dose to 85 days after dose administration

Study Arms (5)

Cohort 1

EXPERIMENTAL

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

Drug: SHR-1222; Drug: Placebo

Cohort 2

EXPERIMENTAL

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

Drug: SHR-1222; Drug: Placebo

Cohort 3

EXPERIMENTAL

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

Drug: SHR-1222; Drug: Placebo

Cohort 4

EXPERIMENTAL

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

Drug: SHR-1222; Drug: Placebo

Cohort 5

EXPERIMENTAL

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

Drug: SHR-1222; Drug: Placebo

Interventions

SHR-1222 DRUG

Pharmaceutical form: water injection Route of administration: subcutaneous

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Placebo DRUG

Pharmaceutical form: water injection Route of administration: subcutaneous

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Eligibility Criteria

• Age: 45 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

2nd Xiangya Hospital of Central South University

Changsha, China

Location

Related Publications (1)

• 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.

  PMID: 34744750 DERIVED

MeSH Terms

Conditions

Osteoporosis

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Zhiguang Zhou, MD

  2nd Xiangya Hospital of Central South University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2019
• First Posted: March 11, 2019
• Study Start: April 15, 2019
• Primary Completion: October 14, 2019
• Study Completion: January 6, 2020
• Last Updated: June 16, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)