Study to Assess PK, Safety and Tolerability in Healthy Subjects

NCT06380699 | Completed Phase 1

• 1 other identifier: HJG-CZQH-QHRD106-I
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Ischemic Stroke

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (5)

Part-A SAD in healthy subjects(Cohort 1-2)

EXPERIMENTAL

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

Part-B MAD in healthy subjects(Cohort 3-5)

EXPERIMENTAL

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

Part-C Healthy subjects SAD placebo

PLACEBO COMPARATOR

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

Part-D Healthy subjects MAD placebo

PLACEBO COMPARATOR

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

Part-E Healthy subjects MAD positive drug

ACTIVE COMPARATOR

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

Interventions

QHRD106 Injection DRUG

PEG-tissue kallikrein-1

Also known as: pegylated(PEG)-tissue kallikrein-1

Part-A SAD in healthy subjects(Cohort 1-2); Part-B MAD in healthy subjects(Cohort 3-5)

Human Urinary Kallidinogenase DRUG

tissue kallikrein-1

Also known as: tissue kallikrein-1

Part-E Healthy subjects MAD positive drug

placebo DRUG

placebo

Part-C Healthy subjects SAD placebo; Part-D Healthy subjects MAD placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female subjects, male and female equally;
• 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);
• Participate voluntarily and sign informed consent to complete the experiment according to the research protocol.

You may not qualify if:

• Subjects who meet one of the following conditions will not be enrolled in the trial:
• 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;
• 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;
• 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;
• postural hypotension;
• α1-antitrypsin deficiency;
• Patients with difficulty in venous blood collection;
• People with a history of fainting needles and fainting blood;
• 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);
• 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;
• Excessive daily consumption of tea, coffee or caffeinated beverages (more than 8 cups per day, 1 cup =250mL) in the 3 months before screening;
• 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;
• Positive alcohol breath test (test result greater than 0.0mg/100mL);
• Hepatitis B surface antigen (HBsAg), hepatitis C virus(HCV) antibody, syphilis antibody and human immunodeficiency virus(HIV) antibody test one or more positive;
• Positive urine screening for drug abuse (including morphine, methamphetamine, ketamine, dimethylene dexamphetamine, tetrahydrocannabinol, cocaine);

Sponsors & Collaborators

• Changzhou Qianhong Bio-pharma Co., Ltd.: lead

Study Sites (1)

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, 210008, China

Location

Related Publications (1)

• Huang L, Sun R, Song H, Chen Z, Hong Y, Yang H, Zhang Y, Wei L, Fei F, Li J. The first-in-human study of QHRD106 functioning as a safe and effective long-acting kallikrein drug potentially aiding ischemic stroke. Expert Opin Investig Drugs. 2024 Dec;33(12):1257-1265. doi: 10.1080/13543784.2024.2430200. Epub 2024 Nov 19.

  PMID: 39545461 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Juan Li, Doctor

  The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2024
• First Posted: April 24, 2024
• Study Start: March 16, 2023
• Primary Completion: November 16, 2023
• Study Completion: December 25, 2023
• Last Updated: July 24, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)