Clinical trial NCT03870100: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Osteoporosis
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-03-11
Enrollment: 50
Sex: ALL
Minimum age (years): 45
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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
timeFrame: Dose administration to 85 days after dose administration
Secondary outcomes:
measure: Assessment of PK parameter-time to maximum concentration (Tmax)
timeFrame: Pre-dose to 85 days after dose administration
measure: Assessment of PK parameter-maximum concentration (Cmax)
timeFrame: Pre-dose to 85 days after dose administration
measure: Assessment of PK parameter-area under curve (AUC)
timeFrame: Pre-dose to 85 days after dose administration
measure: Assessment of PD parameter-change in serum C-telopeptide (sCTx) from baseline
timeFrame: Pre-dose to 85 days after dose administration
measure: Assessment of PD parameter-change in aminoterminal propeptide type-1 procollagen (P1NP) from baseline
timeFrame: Pre-dose to 85 days after dose administration
measure: Assessment of PD parameter-change in osteocalcin from baseline
timeFrame: Pre-dose to 85 days after dose administration
measure: Assessment of PD parameter-change in bone-specific alkaline phosphatase (BSAP) from baseline
timeFrame: Pre-dose to 85 days after dose administration
measure: Assessment of PD parameter-change in areal bone mineral density of lumbar spine (L1-L4 mean T value) from baseline
timeFrame: Pre-dose to 85 days after dose administration
measure: Assessment of PD parameter-change in areal bone mineral density of collum femoris (T value) from baseline
timeFrame: Pre-dose to 85 days after dose administration
measure: Assessment of PD parameter-change in volumetric bone mineral density of lumbar spine (L1-L4 mean T value) from baseline
timeFrame: Pre-dose to 85 days after dose administration
measure: Assessment of PD parameter-change in volumetric bone mineral density of collum femoris (T value) from baseline
timeFrame: Pre-dose to 85 days after dose administration
measure: Antidrug antibody concentration
timeFrame: Pre-dose to 85 days after dose administration
Other outcomes:
Locations:
city: Changsha
country: China
facility: 2nd Xiangya Hospital of Central South University
Study officials:
affiliation: 2nd Xiangya Hospital of Central South University
name: Zhiguang Zhou, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.