Study to Assess PK, Safety and Tolerability in Healthy Subjects

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

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

Study Overview

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

Detailed Description

Three dose groups were initially set up. The experimental groups were increased from low to high dose according to the principle of increasing dose, and Urinary kallidinogenase for injection was added as the positive control group. All the selected subjects in the experimental group were given the drug once. Combined with the existing human PK and safety test data, the expected human exposure of the dose group to be increased was still in the range of the lowest safe exposure proved by preclinical toxicology studies, and the safety of the dose to be increased was controllable in humans. The positive control group could be carried out at any time during the single dose increasing stage, and the positive control drug was given once a day for 7 consecutive days.n the stage of multiple dose escalation, QHRD106 injection is intended to be administered in 5600IU, 8400 IU and 12600 IU dosage groups. When the single dose tolerance observation of each dose is completed and the dose escalation termination standard is not reached, the corresponding dose multiple dose escalation study can be selected. Ten subjects in each group were given medicine once a week for 4 consecutive times.

• Study Type: Interventional
• Enrollment (Actual): 56
• 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 dexamphetamine, 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, ixazomib 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, contraceptive 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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part-A SAD in healthy subjects(Cohort 1-2); A randomized, double-blinded, positive drug and placebo-controlled, single ascending dose (SAD) study in healthy male and female subjects. Subjects will receive QHRD106 by intramuscular-injection (im).	Drug: QHRD106 Injection; PEG-tissue kallikrein-1; Other Names: pegylated(PEG)-tissue kallikrein-1
Experimental: Part-B MAD in healthy subjects(Cohort 3-5); A randomized, double-blinded, positive drug and placebo-controlled, multiple ascending dose (MAD) study in healthy male and female subjects. Subjects will receive QHRD106 by intramuscular-injection (im).	Drug: QHRD106 Injection; PEG-tissue kallikrein-1; Other Names: pegylated(PEG)-tissue kallikrein-1
Placebo Comparator: Part-C Healthy subjects SAD placebo; A randomized, double-blinded, positive drug and placebo-controlled, single ascending dose (SAD) study in healthy male and female subjects. Subjects will receive placebo by intramuscular-injection (im).	Drug: placebo; placebo
Placebo Comparator: Part-D Healthy subjects MAD placebo; A randomized, double-blinded, positive drug and placebo-controlled, single ascending dose (SAD) study in healthy male and female subjects. Subjects will receive placebo by intramuscular-injection (im).	Drug: placebo; placebo
Active Comparator: Part-E Healthy subjects MAD positive drug; A randomized, double-blinded, positive drug and placebo-controlled, single ascending dose (SAD) study in healthy male and female subjects. Subjects will receive Human Urinary Kallidinogenase by Intravenous infusion (iv).	Drug: Human Urinary Kallidinogenase; tissue kallikrein-1; Other Names: tissue kallikrein-1

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 events in different dose groups and placebo groups were calculated and listed.	Up to 43 days after final dose
Plasma measurements of QHRD106	The concentration of a single dose was measured at 2 different doses, and the concentration of a multiple dose was measured at 3 different doses	Up to 43 days after final dose
Concentration of bradykinin in plasma	The concentration of a single dose was measured at 2 different doses, and the concentration of a multiple dose was measured at 3 different doses	Up to 43 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): March 16, 2023
• Primary Completion (Actual): November 16, 2023
• Study Completion (Actual): December 25, 2023

Study Registration Dates

• First Submitted: April 16, 2024
• First Submitted That Met QC Criteria: April 21, 2024
• First Posted (Actual): April 24, 2024

Study Record Updates

• Last Update Posted (Actual): July 24, 2024
• Last Update Submitted That Met QC Criteria: July 23, 2024
• Last Verified: July 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-I

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