Back to resultsThe PK/PD Study of A Single Subcutaneous Injection of SHR-1222 in Healthy Subjects
Primary Purpose
Osteoporosis
Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
SHR-1222
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Osteoporosis
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.
Sites / Locations
- 2nd Xiangya Hospital of Central South University
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Cohort 3
Cohort 4
Cohort 5
Arm Description
A single subcutaneous injection of SHR-1222 dose 1 versus placebo
A single subcutaneous injection of SHR-1222 dose 2 versus placebo
A single subcutaneous injection of SHR-1222 dose 3 versus placebo
A single subcutaneous injection of SHR-1222 dose 4 versus placebo
A single subcutaneous injection of SHR-1222 dose 5 versus placebo
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Assessment of PK parameter-time to maximum concentration (Tmax)
Assessment of PK parameter-maximum concentration (Cmax)
Assessment of PK parameter-area under curve (AUC)
Assessment of PD parameter-change in serum C-telopeptide (sCTx) from baseline
Assessment of PD parameter-change in aminoterminal propeptide type-1 procollagen (P1NP) from baseline
Assessment of PD parameter-change in osteocalcin from baseline
Assessment of PD parameter-change in bone-specific alkaline phosphatase (BSAP) from baseline
Assessment of PD parameter-change in areal bone mineral density of lumbar spine (L1-L4 mean T value) from baseline
by dualenergy X-ray absorptiometry
Assessment of PD parameter-change in areal bone mineral density of collum femoris (T value) from baseline
by dualenergy X-ray absorptiometry
Assessment of PD parameter-change in volumetric bone mineral density of lumbar spine (L1-L4 mean T value) from baseline
by quantitative computed tomography
Assessment of PD parameter-change in volumetric bone mineral density of collum femoris (T value) from baseline
by quantitative computed tomography
Antidrug antibody concentration
Full Information
NCT ID
NCT03870100
First Posted
February 25, 2019
Last Updated
June 14, 2020
Sponsor
Jiangsu HengRui Medicine Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT03870100
Brief Title
The PK/PD Study of A Single Subcutaneous Injection of SHR-1222 in Healthy Subjects
Official Title
Use the Protocol Title. The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study Following A Single Subcutaneous Injection of SHR-1222 in Healthy Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
April 15, 2019 (Actual)
Primary Completion Date
October 14, 2019 (Actual)
Study Completion Date
January 6, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jiangsu HengRui Medicine Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoporosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
A single subcutaneous injection of SHR-1222 dose 1 versus placebo
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
A single subcutaneous injection of SHR-1222 dose 2 versus placebo
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
A single subcutaneous injection of SHR-1222 dose 3 versus placebo
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
A single subcutaneous injection of SHR-1222 dose 4 versus placebo
Arm Title
Cohort 5
Arm Type
Experimental
Arm Description
A single subcutaneous injection of SHR-1222 dose 5 versus placebo
Intervention Type
Drug
Intervention Name(s)
SHR-1222
Intervention Description
Pharmaceutical form: water injection Route of administration: subcutaneous
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Pharmaceutical form: water injection Route of administration: subcutaneous
Primary Outcome Measure Information:
Title
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
Time Frame
Dose administration to 85 days after dose administration
Secondary Outcome Measure Information:
Title
Assessment of PK parameter-time to maximum concentration (Tmax)
Time Frame
Pre-dose to 85 days after dose administration
Title
Assessment of PK parameter-maximum concentration (Cmax)
Time Frame
Pre-dose to 85 days after dose administration
Title
Assessment of PK parameter-area under curve (AUC)
Time Frame
Pre-dose to 85 days after dose administration
Title
Assessment of PD parameter-change in serum C-telopeptide (sCTx) from baseline
Time Frame
Pre-dose to 85 days after dose administration
Title
Assessment of PD parameter-change in aminoterminal propeptide type-1 procollagen (P1NP) from baseline
Time Frame
Pre-dose to 85 days after dose administration
Title
Assessment of PD parameter-change in osteocalcin from baseline
Time Frame
Pre-dose to 85 days after dose administration
Title
Assessment of PD parameter-change in bone-specific alkaline phosphatase (BSAP) from baseline
Time Frame
Pre-dose to 85 days after dose administration
Title
Assessment of PD parameter-change in areal bone mineral density of lumbar spine (L1-L4 mean T value) from baseline
Description
by dualenergy X-ray absorptiometry
Time Frame
Pre-dose to 85 days after dose administration
Title
Assessment of PD parameter-change in areal bone mineral density of collum femoris (T value) from baseline
Description
by dualenergy X-ray absorptiometry
Time Frame
Pre-dose to 85 days after dose administration
Title
Assessment of PD parameter-change in volumetric bone mineral density of lumbar spine (L1-L4 mean T value) from baseline
Description
by quantitative computed tomography
Time Frame
Pre-dose to 85 days after dose administration
Title
Assessment of PD parameter-change in volumetric bone mineral density of collum femoris (T value) from baseline
Description
by quantitative computed tomography
Time Frame
Pre-dose to 85 days after dose administration
Title
Antidrug antibody concentration
Time Frame
Pre-dose to 85 days after dose administration
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhiguang Zhou, MD
Organizational Affiliation
2nd Xiangya Hospital of Central South University
Official's Role
Principal Investigator
Facility Information:
Facility Name
2nd Xiangya Hospital of Central South University
City
Changsha
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34744750
Citation
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.
Results Reference
derived
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The PK/PD Study of A Single Subcutaneous Injection of SHR-1222 in Healthy Subjects
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