A Study to Evaluate the Safety, Tolerability and Pharmacokinetics Pharmacodynamics of SHR-2010 by Intravenously/Subcutaneously in Healthy Subject

Phase 1

Completed

• Conditions: IgA Nephropathy
• Interventions: Drug: SHR-2010 injection placebo; Drug: SHR-2010 injection

• Registration Number: NCT05398510
• Lead Sponsor: Guangdong Hengrui Pharmaceutical Co., Ltd

Brief Summary

The study is being conducted to Evaluate the Safety, Tolerability and Pharmacokinetics pharmacodynamics of SHR-2010 by intravenously/subcutaneously in Healthy Subject.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-05-26
• Study First Submitted QC: 2022-05-26
• Study First Posted: 2022-06-01
• Study Start: 2022-06-30
• Status Verified: 2023-03
• Primary Completion: 2023-03-10
• Study Completion: 2023-03-10
• Last Update Submitted: 2023-03-22
• Last Update Posted: 2023-03-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 61

Inclusion Criteria

1. Able and willing to provide a written informed consent.
2. Male or non-pregnant, non-lactating female ages 18 to 55 years old.
3. Weight ≥ 45 kg, and body mass index (BMI) must range from 18 to 28 kg/m2 .
4. Healthy subjects as determined by absence of clinically significant abnormalities on medical history, physical examination, vital signs, 12-lead ECG and clinical laboratory tests performed at screening or baseline period.
5. Subjects must be willing to use a highly effective method of contraception as deemed appropriate by the investigator throughout the study and for at least 3 months after the last study drug administration.

Exclusion Criteria

1. Evidence or history of serious cardiovascular, hepatic, renal, gastrointestinal, psychiatric, neurological, haematological, or metabolic diseases within 5 years.
2. Subjects with tuberculosis diagnosed by Interferon Gamma Release Assays (IGRA) or chest X-ray.
3. Subjects had any surgery within the past 6 months before screening or planned to undergo surgery during the study period.
4. Estimated Glomerular Filtration Rate（eGFR）<90 mL/min/1.73m2.
5. Positive for hepatitis (including hepatitis B and C), HIV or syphilis at screening.
6. Systolic blood pressure (SBP) > 140 mm Hg or < 90 mm Hg, or diastolic blood pressure (DBP) > 90 mm Hg or < 60 mm Hg and has been considered clinically significant.
7. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or gamma-glutamyl transferase (GGT) ≥2.0 x ULN, or total bilirubin ≥1.5 x ULN.
8. Clinically significant abnormal 12-lead ECG at screening (male with QTcF > 450 ms or female with QTcF > 470 ms).
9. Female subjects who had unprotected sexual behaviour within 14 days before screening.
10. Positive for alcohol breath test at screening or baseline period.
11. Positive urinary drug test at screening or baseline period.
12. Blood collection is difficult or cannot tolerate venipuncture blood collection.
13. Allergic to any ingredient or component in the study drug.
14. Subjects who have taken any prescription drugs, over-the-counter drugs, or Chinese herbal medicine within 14 days prior to using the study drug.
15. Subjects who smoked more than 5 cigarettes daily in the 1 month before screening.
16. History of regular alcohol consumption exceeding 3 units/day for women or 5 units/day for men, more than twice per week (1 unit = 150 ml of beer or 50 ml of wine or 17 ml of alcoholic spirits) within 3 months before screening.
17. Participated in any other clinical trials of any drug or medical device within 3 months before screening.
18. Donated blood or blood products or had substantial loss of blood (more than 400 mL) within 1 month before screening, or received any blood or blood products within 2 months prior to screening.
19. Subjects who received live (attenuated) vaccine within 1 month prior to screening or consider getting a vaccination during the study.
20. The employee of investigator or study centre, with direct involvement in the proposed study.
21. The investigators determined that other conditions were inappropriate for participation in this clinical trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo for intravenously/subcutaneously	SHR-2010 injection placebo	Treatment for intravenously: 6 dose groups； Treatment for subcutaneously: 3 dose groups.
Treatment for intravenously/subcutaneously	SHR-2010 injection	Treatment for intravenously: 6 dose groups； Treatment for subcutaneously: 3 dose groups.

Primary Outcome Measures

Name	Time	Method
Safety and tolerability: Incidence of subjects with adverse events (AEs)	Baseline up to Day 85	Incidence of AEs, including any abnormal findings in vital signs, and/or physical examination and/or clinical laboratory assessments and/or 12-lead ECG evaluation and/or IGRA.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK) parameter: AUC0-t for SHR-2010	Baseline up to Day 85	AUC0-t: Area under the plasma concentration-time curve from time zero to the time of last quantifiable analyte concentration
Pharmacokinetics (PK) parameter: t1/2 for SHR-2010	Baseline up to Day 85	t1/2: Terminal half-life
Pharmacokinetics (PK) parameter: AUC0-∞ for SHR-2010	Baseline up to Day 85	AUC0-∞: Area under the plasma concentration-time curve from time zero extrapolated to infinity
Pharmacokinetics (PK) parameter: CL of SHR-2010 for administration intravenously	Baseline up to Day 85	CL: Clearance
Pharmacokinetics (PK) parameter: Cmax for SHR-2010	Baseline up to Day 85	Cmax: Maximum plasma concentration
Pharmacokinetics (PK) parameter: V of SHR-2010 for administration intravenously	Baseline up to Day 85	V: Volume of distribution
Pharmacokinetics (PK) parameter: V/F of SHR-2010 for administration subcutaneously	Baseline up to Day 85	V/F: Apparent volume of distribution
Pharmacokinetics (PK) parameter: Tmax for SHR-2010	Baseline up to Day 85	Tmax: Time to reach maximum plasma concentration
Pharmacokinetics (PK) parameter: CL/F of SHR-2010 for administration subcutaneously	Baseline up to Day 85	CL/F: Apparent clearance
Pharmacodynamics (PD): C4b level in the serum	Baseline up to Day 85	C4b level in the serum.
Immunogenicity: Proportion of anti-drug antibodies (ADA) positive subjects	Baseline up to Day 85	Proportion of anti-drug antibodies (ADA) positive subjects.
Pharmacokinetics (PK) parameter: Bioavailability (F) of SHR-2010	Baseline up to Day 85	Bioavailability of SHR-2010 for administration subcutaneously.

Trial Locations

Locations (1)

The Affiliated Hospital of Qingdao University; 🇨🇳 Qingdao, Shandong, China