TP03HN106 in Patients With Critical Limb Ischemia

A Single Arm Clinical Study Evaluating the Safety, Tolerability, and Efficacy of Multiple Intravenous Administration of TP03HN106 in Patients With Critical Limb Ischemia

Critical limb ischemia (CLI) is the most severe ischemic stage in peripheral arterial disease (PAD) of the lower limbs, characterized by decreased walking ability, resting pain (lasting for more than 2 weeks), ulcers, and gangrene, which seriously affect the quality of life of patients. Some patients may even face amputation or death. Thrombosis is an important pathological feature of CLI. TP03HN106 can promote thrombolysis, thus having a therapeutic effect on CLI.

Study Overview

• Status: Recruiting
• Conditions: Critical Limb Ischemia
• Intervention / Treatment: Drug: TP03HN106

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chunying Guo; Phone Number: 86-15919440001; Email: guocy@talengen-pharma.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: Caifang Ni; Phone Number: 86-13706200115; Email: cir.nicaifang@vip.163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. When signing the informed consent form, the age should be ≥ 18 years old, regardless of gender;
2. Clinically diagnosed as a patient with Critical limb ischemia, with a Rutherford score of 4-6.
3. Patients who are unable to undergo interventional surgical treatment, or whose previous interventional surgical treatment is ineffective, or who are unwilling to undergo any intervention or surgical treatment, and can only receive conventional antiplatelet and vasodilator drugs (before baseline, antiplatelet and vasodilator drugs must be used for at least 1 week);
4. During the screening period, lower limb artery color ultrasound or lower limb computed tomography angiography (CTA) showed severe stenosis or occlusion of one or more of the common iliac artery, external iliac artery, common femoral artery, superficial femoral artery, popliteal artery, anterior tibial artery, posterior tibial artery, and fibular artery;
5. During the screening period, if there are severe symptoms of lower limb ischemia, meeting any of the following symptoms is sufficient: There is limb rest pain caused by lower limb ischemia, with a disease duration of ≥ 2 weeks, and a VAS score of ≥ 40mm and < 100mm before the first administration; There are limb tissue ulcers caused by lower limb ischemia, with a disease duration of ≥ 2 weeks and limb ulcers (4cm2 ≤ maximum single ulcer area ≤ 25cm2);
6. All subjects with fertility or their spouses must take effective contraceptive measures within 3 months after signing the informed consent form until the completion of the trial;
7. The subjects voluntarily give informed consent and sign an informed consent form (if the subjects and/or their guardians lack reading ability and cannot understand the content of the informed consent, they need to sign together with a fair witness), fully understand the methods and procedures of the experiment, and be able to provide biological samples for testing related indicators in accordance with the experiment requirements.

Exclusion Criteria:

1. Subjects who are known to be allergic to the investigational drug, its excipients, or other human blood products;
2. Patients with limb gangrene greater than 4 cm2;
3. Patients currently suffering from malignant tumor diseases (including those who have previously had malignant tumors but have not been cured);
4. Screening period for patients with liver and kidney failure:
5. Patients who require hemodialysis;
6. Those who have experienced cerebral infarction or cerebral hemorrhage within 3 months prior to signing the informed consent form;
7. During the screening period, subjects with mental illness, obvious mental disorders or epilepsy, including other individuals with no behavioral or cognitive abilities;
8. Hypertensive patients (SBP ≥ 160mmHg and/or DBP ≥ 100mmHg) who cannot be controlled after standardized treatment in the screening period;
9. Individuals who have received fresh plasma, cold precipitates, or blood products containing TP03HN106 components within one month prior to signing the informed consent form;
10. Those who have participated in clinical trials of other drugs or medical devices within one month before signing the informed consent form;
11. Those who have undergone or plan to undergo surgery during the trial period within one month prior to signing the informed consent form;
12. Alcoholism and/or psychoactive substances, drug abusers and dependents (alcoholism standard: the weekly alcohol intake is more than 21 units (male) and 14 units (female) (1 unit=360 mL beer; or 150 mL wine; or 45 mL white spirit);
13. Miscarriage or termination of pregnancy less than 3 months prior to signing the informed consent form, pregnant women and lactating women (currently breastfeeding or not artificially breastfeeding but less than 6 months after delivery);
14. Poor compliance or any other situation that the researcher deems unsuitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment group

Drug: TP03HN106; During the dose escalation phase, subjects will undergo a dose escalation trial of intravenous injection of TP03HN106 for 5 consecutive days to evaluate the safety and tolerance of the subjects to the injection dose of TP03HN106. The preset initial dose for this experiment is 10U/kg, with gradient doses of 20, 30, 40, and 50U/kg. Observe the subjects receiving the investigational drug for any adverse events (AEs) after daily intravenous injection. During the maintenance treatment phase, the subjects will undergo two consecutive treatment courses at the final dose during the dose escalation phase. During each treatment course, subjects will complete the collection of efficacy and safety data for 14 consecutive days of medication (administered every 2 days) and 14 days of discontinuation to evaluate the efficacy and safety of TP03HN106 for subjects with critical limb ischemia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall clinical treatment efficacy rate	The VAS score or ulcer area decreases by ≥ 50% compared to baseline when administering day 62, it is considered a clinically effective case. The overall clinical efficacy of patient treatment is calculated according to the following formula: Overall clinical treatment effectiveness rate=(number of clinically effective cases/total cases) × 100% When the calculated overall clinical success rate is ≥ 70%, the entire clinical trial is considered successful.	Day 62

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ankle brachial index, ABI	Changes in ABI of subjects (applicable to patients with ulcers) compared to baseline during administration of day 6, day 21, day 34, day 49, and day 62 ABI:The ratio of ankle artery systolic pressure to ipsilateral brachial artery systolic pressure	Baseline, day 6, day 21, day 34, day 49, and day 62
TcPO2	Changes in TcPO2 of subjects (applicable to patients with ulcers) compared to baseline during administration of day 6, day 21, day 34, day 49, and day 62 TcPO2: transcutaneous oxygen partial pressure	Baseline, day 6, day 21, day 34, day 49, and day 62
TBI	Changes in TBI of subjects compared to baseline during administration of day 6, day 21, day 34, day 49, and day 62 TBI: The ratio of toe artery systolic pressure to ipsilateral brachial artery systolic pressure	Baseline, day 6, day 21, day 34, day 49, and day 62
Rutherford grading	Changes in Rutherford grading of subjects compared to baseline during administration of day 6, day 21, day 34, day 49, and day 62	Baseline, day 6, day 21, day 34, day 49, and day 62
Overall clinical treatment efficacy rate	The VAS score or ulcer area decreases by ≥ 50% compared to baseline when administering day 6, day 14, day 21, day 34, day 49, it is considered a clinically effective case. The overall clinical efficacy of patient treatment is calculated according to the following formula: Overall clinical treatment effectiveness rate=(number of clinically effective cases/total cases) × 100% When the calculated overall clinical success rate is ≥ 70%, the entire clinical trial is considered successful.	Day 6, day 14, day 21, day 34, day 49

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coagulation function indicators	Changes in coagulation function of subjects compared to baseline during administration of day 6, day 21, day 34, day 49, and day 62	Baseline, day 6, day 21, day 34, day 49, and day 62
Fibrinogen degradation products (FDP)	Changes in FDP of subjects compared to baseline during administration of day 6, day 21, day 34, day 49, and day 62	Baseline, day 6, day 21, day 34, day 49, and day 62
Thrombosis 4 items	Changes in thrombosis 4 items of subjects compared to baseline during administration of day 6, day 21, day 34, day 49, and day 62	Baseline, day 6, day 21, day 34, day 49, and day 62
Computed tomography perfusion (CTP)	Changes in blood volume of subjects compared to baseline during administration of day 34 and day 62	Baseline,day 34, day 62
Infrared thermal imaging	Measure the temperature of the feet and lower leg	Baseline,day 34, day 62
Computed tomography perfusion (CTP)	Changes in blood flow of subjects compared to baseline during administration of day 34 and day 62	Baseline,day 34, day 62

Collaborators and Investigators

• Sponsor: Talengen Institute of Life Sciences, Shenzhen, P.R. China.
• Collaborators: The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2024
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: June 20, 2024
• First Submitted That Met QC Criteria: June 25, 2024
• First Posted (Actual): July 1, 2024

Study Record Updates

• Last Update Posted (Actual): April 15, 2025
• Last Update Submitted That Met QC Criteria: April 10, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Peripheral Arterial Disease; Chronic Limb-Threatening Ischemia; Ischemia
• Other Study ID Numbers: TP03HN106-CLI-IIT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes