[Recruitment] Phase III Clinical Trial of Recombinant Human Hepatocyte Growth Factor Naked Plasmid Injection for the Treatment of Severe Lower Limb Ischemic Disease Grade 4 (Rest Pain) & Grade 5 (Ulceration) according to Rutherford Classification

I. Introduction to the Investigational Drug

“The Recombinant Human Hepatocyte Growth Factor Naked Plasmid Injection” is a novel therapeutic biological product developed by Beijing Northland Biotechnology Co., Ltd. This product has not yet been approved for marketing in China. The drug is a gene therapy agent; when injected into the muscles of ischemic areas, it may promote the formation of new collateral vessels, thereby enhancing blood supply to the ischemic tissues. Consequently, it may be used to treat lower-limb arterial ischemic diseases such as atherosclerotic occlusion of the lower limbs, thrombo-obliterating endarteritis, and diabetic limb arterial occlusion. The drug has completed Phase I and Phase II clinical trials, and preliminary results have demonstrated good efficacy and safety. Currently, Phase III clinical trials are underway, and patient recruitment is ongoing.

II. Legality

This product has received clinical research approval from the National Medical Products Administration, with approval number 2017L04713. A Phase III clinical study is currently underway nationwide.

III. Research-related expenses

After screening and meeting the inclusion criteria, you will receive free access to standard medications for treating lower-limb arterial ischemic disease (cilostazol or beraprost sodium) as well as investigational drugs. You will also receive free DSA or CTA examinations and a series of related medical tests, along with transportation and nutritional allowances and professional guidance from physicians.

IV. Visiting Plan

The subjects received a single intramuscular injection on Days 0, 14, and 28 of the study. They also underwent a total of nine follow-up visits and medical examinations during the screening period, as well as on Days 0, 14, 28, 60, 90, 120, 150, and 180. The trial duration was 180 days.

V. Recruitment Target

Patients with lower-limb arterial ischemic disease who meet the following criteria (please consult the study physician for specific standards) may participate in this study:

1. Age ≥ 20 years and ≤ 80 years (at the time of signing the informed consent), gender unrestricted;

2. Patients diagnosed with lower limb arterial ischemic disease based on DSA or CTA, in conjunction with medical history and clinical manifestations, and who are classified as Rutherford Grade 4 (rest pain) or Rutherford Grade 5 (with ulcers), must simultaneously meet the following criteria. (If a subject has lower limb arterial ischemic disease in both limbs, the investigator will decide which limb to enroll in the study.)

● Resting ankle systolic blood pressure on the affected limb (dorsalis pedis artery or posterior tibial artery) ≤70 mmHg, or ABI ≤0.5, or TcPO2 <30 mmHg;

● Patients with severe stenosis (≥70%) or occlusion of the superficial femoral artery, popliteal artery, or infrapopliteal arteries, confirmed by DSA or CTA within 3 months prior to randomization.

3. Chronic lower limb arterial ischemia accompanied by rest pain and simultaneously meeting the following criteria:

● Resting pain lasting more than 2 weeks at the time of signing the informed consent form;

● Within 7 days prior to randomization, subjects must have completed at least 5 days of pain assessments using the Numerical Rating Scale (NRS), with an average daily pain score of ≥4 (on a scale of 0 to 10).

or patients with chronic lower limb arterial ischemia who have ulcers and simultaneously meet the following requirements:

◆ The arterial ischemic ulcer must have persisted for at least 2 weeks at the time of signing the informed consent form.

◆ When signing the informed consent form, the area of a single ulcer ≤ 10 cm²;

◆ If multiple ulcers are present simultaneously in the affected limb at the time of signing the informed consent form, the total number of ulcers shall not exceed 3.

◆ During the trial, basic ulcer care (following the standard ulcer care protocol) must be maintained to prevent worsening of infection.

◆ The ulcer does not expose the bone or joint capsule;

◆ If gangrene is present at the same time, it is limited to localized toe gangrene.

4. During the trial, participants agree to use the background therapy medications as required and to complete and accurately record their diaries on time. During the screening period, adherence to the background therapy medications and diary completion must be at least 70%.

5. During the trial, participants agree to use appropriate contraceptive measures; female subjects of childbearing age must have a negative blood pregnancy test.

6. Those who sign the informed consent form.

6. Contact Information

Our trial, led by Peking Union Medical College Hospital, is currently being conducted nationwide.

You can choose a suitable hospital, contact them by phone, or visit the department for a detailed discussion.