Study to Assess PK, Safety and Tolerability Early in Healthy Subjects

Phase I Clinical Study of Tolerability, Safety and Pharmacokinetics of QHRD106 Injection in Chinese Healthy Subjects With Single Doses

The purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of QHRD106 early in Chinese healthy subjects with single doses.

Study Overview

• Status: Completed
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: placebo; Drug: QHRD106 Injection

Detailed Description

Eight dose groups were initially set up. The experimental groups were increased from low to high dose according to the principle of increasing dose, and Placebo was added as the control group. All the selected subjects in the experimental group were given the drug once.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Drum Tower Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy male or female subjects, male and female equally;
2. Aged between 18 and 50 at the time of screening (including boundary values); Male weight ≥50.0kg, female weight ≥45.0kg; All subjects had a body mass index (BMI) between 19 and 28kg/m2 (including boundary values);
3. Participate voluntarily and sign informed consent to complete the experiment according to the research protocol.

Exclusion Criteria:

Subjects who meet one of the following conditions will not be enrolled in the trial:

1. a person who is allergic to, or is allergic to, 2 or more drugs or foods, or is known to have a history of allergy to the test preparation and any of its components or related preparations;
2. Patients with a history of clinically serious diseases such as nervous system, blood circulatory system, digestive system, urinary system, respiratory system, immune system, endocrine system, malignant tumor, mental and metabolic abnormalities, or any clinically significant diseases judged by researchers to be in an active period or unstable state;
3. Based on vital signs (including sitting blood pressure, pulse, and body temperature), physical examination, 12-lead electrocardiogram examination, and laboratory examination (including routine blood routine, urine routine, blood biochemistry, and coagulation function), the investigator determined that the abnormality was clinically significant;
4. postural hypotension;
5. α1-antitrypsin deficiency;
6. Patients with difficulty in venous blood collection;
7. People with a history of fainting needles and fainting blood;
8. A history of drug abuse within the last two years (including repeated and heavy use of various narcotic drugs and psychotropic substances for non-medical purposes);
9. Excessive smoking within 3 months before screening (average > 5 cigarettes/day) or unable to stop using any tobacco products during the test period or smokers within 48 hours before screening;
10. Excessive daily consumption of tea, coffee or caffeinated beverages (more than 8 cups per day, 1 cup =250mL) in the 3 months before screening;
11. alcoholics (i.e. men drinking more than 28 standard units per week, women drinking more than 21 standard units per week, 1 standard unit containing 14g of alcohol, such as 360mL beer or 45mL spirits with 40% alcohol or 150mL wine) or regular drinkers (i.e. more than 14 standard units per week) in the six months prior to screening;
12. Positive alcohol breath test (test result greater than 0.0mg/100mL);
13. Hepatitis B surface antigen (HBsAg), hepatitis C virus(HCV) antibody, syphilis antibody and human immunodeficiency virus(HIV) antibody test one or more positive;
14. Positive urine screening for drug abuse (including morphine, methamphetamine, ketamine, dimethylene dioxyamphetamine, tetrahydrocannabinol, cocaine);
15. Abnormal chest X-ray or CT findings with clinical significance;
16. Abdominal B-ultrasonography (liver, bile, pancreas, spleen and kidney) with abnormal results and clinical significance;
17. Severe acute bacterial, viral or fungal infection within 4 weeks prior to screening;
18. Patients who had used any protease drugs (such as chylase, indinavir sulfate, ritonavir, bortezomib, isazzomib citrate, etc.) within 4 weeks before screening;
19. Use of any prescription or over-the-counter drugs, as well as any functional vitamins or Chinese herbal products within 2 weeks prior to screening;
20. Blood donation or blood loss greater than 400mL within 3 months before screening (except physiological blood loss);
21. Vaccinated within 1 month before screening, or planned to be vaccinated during the study period and within 1 month after the study ends;
22. Those who had undergone surgery within 3 months prior to screening or planned to undergo surgery during the trial;
23. Participants who participated in any drug clinical trial as a subject within 3 months before enrollment;
24. have consumed a special diet (including grapefruit, chocolate, tea, cola, or any food or beverage containing caffeine, alcoholic beverage, or other food or beverage that affects the absorption, distribution, metabolism, or excretion of drugs) in the 48 hours prior to screening;
25. The subjects or their partners do not wish to use one or more non-drug contraceptive methods (such as total abstinence, condoms, Icontraceptive rings, ligation, etc.) for contraception during the trial period or have pregnancy plans within 3 months after the end of the study; Or screening women with positive pregnancy tests or breastfeeding women;
26. With magnetic resonance examination contraindications: metal implant, claustrophobia, etc.;
27. Other situations in which the investigator considers that participation in the trial may not be appropriate. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part-A SAD in healthy subjects(Cohort 1-8); A randomized, double-blinded, placebo-controlled, single ascending dose (SAD) study in healthy male and female subjects. Subjects will receive QHRD106 by intramuscular-injection (im).	Drug: QHRD106 Injection; 250IU~8400IU,pegylated(PEG)-tissue kallikrein-1; Other Names: pegylated(PEG)-tissue kallikrein-1
Experimental: Part-B Healthy subjects SAD placebo; A randomized, double-blinded, placebo-controlled, single ascending dose (SAD) study in healthy male and female subjects. Subjects will receive placebo by intramuscular-injection (im).	Drug: placebo; placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety as assessed by incidence, severity, and causality of adverse events	The frequency and number of adverse events, adverse reactions and serious adverse	Up to 36 days after final dose
Plasma measurements of QHRD106	The concentration of a single dose was measured at 8 different doses	Up to 36 days after final dose

Collaborators and Investigators

• Sponsor: Changzhou Qianhong Bio-pharma Co., Ltd.
• Investigators: Principal Investigator: Juan Li, Doctor, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2021
• Primary Completion (Actual): July 22, 2022
• Study Completion (Actual): January 6, 2023

Study Registration Dates

• First Submitted: April 25, 2024
• First Submitted That Met QC Criteria: April 25, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Physiological Effects of Drugs; Coagulants; Reproductive Control Agents; Fertility Agents; Fertility Agents, Male; Kallikreins
• Other Study ID Numbers: HJG-CZQH-QHRD106

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No