Safety and Efficacy Study Using Gene Therapy for Critical Limb Ischemia

NCT01548378 | Completed Phase 2 DMC

• 1 other identifier: NL003CLI-II
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study is to evaluate whether intramuscular injections of NL003 into the calf is safe and effective in the treatment of critical limb ischemia

Conditions

Arterial Occlusive Disease; Ulcers; Ischemia; Peripheral Vascular Disease

Keywords

HGF; Gene; Critical Limb Ischemia

Outcome Measures

Primary Outcomes (2)

• The difference in ulcer area between baseline and the D180.

  Rutherford 5 only

  Day180

• The difference in pain level between baseline and the D180 as determined by VAS

  Day 180

Secondary Outcomes (9)

• Change in tissue oxygenation (TcPO2) from baseline to D180

  Day0、14、28、60、90、180

• Difference in percentage of pain level decreased by 50% determined by VAS from baseline to D180

  Day0、14、28、60、90、180

• Difference in percentage of ulcer area decreased by 50% from baseline to D180

  Day0、14、28、60、90、180

• Difference in ABI and TBI from baseline to D180

  Day0、14、28、60、90、180

• Difference in QOL score (VascuQol) from baseline to D180

  Day0、14、28、60、90、180

Study Arms (4)

High Dose

EXPERIMENTAL

Patients in this treatment group will receive 8mg NL003 respective in D0、14、28

Genetic: NL003

Middle Dose

EXPERIMENTAL

Patients in this treatment group will receive 6mg NL003 respective in D0、14、28

Genetic: NL003

Low Dose

EXPERIMENTAL

Patients in this treatment group will receive 4mg NL003 in D0、14、28

Genetic: NL003

Placebo

PLACEBO COMPARATOR

Patients in this group will receive normal saline respective in D0、14、18

Other: Normal Saline

Interventions

NL003 GENETIC

Day 0: 8mg of NL003 (32 injections of 0.5ml of NL003) Day 14: 8mg of NL003 (32 injections of 0.5ml of NL003) Day 28: 8mg of NL003 (32 injections of 0.5ml of NL003)

Also known as: HGF plasmid, pCK-HGF-X7

High Dose

Normal Saline OTHER

Day 0: 16ml of Normal Saline (32 injections ) Day 14: 16ml of Normal Saline (32 injections ) Day 28: 16ml of Normal Saline (32 injections )

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, between 30 and 80years of age
• Diagnosis of critical limb ischemia(ASO、TAO、DAO)，Rutherford Class 4 or 5, including:
• A resting ankle systolic pressure of ≤ 70 mmHg in the affected limb; or
• A resting toe systolic pressure of ≤ 50 mmHg in the affected limb; or
• For patients in which measurement of ankle systolic pressure is not feasible , TcPO2 ≤ 30mmHg; Only unilateral affected limb receive treatment。
• Significant stenosis (≥ 75%) of one or more of the following arteries:
• superficial femoral, popliteal as verified by angiography（DSA、CTA、MRA） within 12 months prior to enrollment
• Be willing to maintain current drug therapy for peripheral arterial disease throughout the course of the study
• Be willing to maintain ulcer treatment
• Be willing to infertility throughout the course of the study
• If the subject is of child-bearing potential, she must have a negative urine pregnancy test result prior to study enrollment
• Tumor screening result is no clinic meaning，including:
• Signing the informed consent document prior to being subjected to any study related procedures

You may not qualify if:

• Subjects who have undergone a successful revascularization procedure or sympathectomy within 12 weeks prior to study entry.
• Acute advanced CLI
• Subjects that will require an amputation in the target leg within 4 weeks, or significant stenosis (≥ 75%) of Aortoiliac
• Subjects with evidence of active infection or deep ulceration exposing bone or tendon in the extremity planned for treatment
• Heart Failure with a NYHA classification of III or IV
• Stroke、myocardial infarction or unstable angina within last 3 months
• Uncontrolled hypertension defined as sustained systolic blood pressure (SBP) \> 180 mmHg or diastolic BP (DBP) \> 110 mmHg
• Ophthalmologic conditions pertinent to proliferative retinopathy or conditions that preclude standard ophthalmologic examination
• Can not correctly describe the symptoms and feeling
• Subjects with advanced liver disease including decompensated cirrhosis, jaundice, ascites or bleeding varices
• Subjects currently receiving immunosuppressive medications chemotherapy, or radiation therapy
• Positive HIV,active Hepatitis B(determined by HBsAb\\ HBcAb\\HBsAg) or C infection
• Elevated PSA unless prostate cancer has been excluded
• Patients with a recent history (\< 5 years) of or new screening finding of malignant neoplasm except basal cell carcinoma or squamous cell carcinoma of the skin (if excised and no evidence of recurrence); patients with family history of colon cancer in any first degree relative are excluded unless they have undergone a colonoscopy in the last 12 months with negative findings
• Subjects requiring \> 100 mg daily of acetylsalicylic acid,COX-2 inhibitor drug(s) or high dose steroids (excepting inhaled steroids)

Sponsors & Collaborators

• Beijing Northland Biotech. Co., Ltd.: lead

Study Sites (9)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100032, China

Location

Beijing Shijitan Hospital

Beijing, Beijing Municipality, 100038, China

Location

Xuanwu Hospital Capital Medical University

Beijing, Beijing Municipality, 100053, China

Location

The General Hospital of the People's Liberation Army

Beijing, Beijing Municipality, 100853, China

Location

Wuhan Union Hospital

Wuhan, Hubei, 430022, China

Location

The Second Xiangya Hospital of Central South University

Changsha, Hunan, China

Location

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, 210008, China

Location

First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

The Second Hospital of Dalian Medical University

Dalian, Liaoning, China

Location

Related Links

• Related Info

MeSH Terms

Conditions

Arterial Occlusive Diseases; Ulcer; Ischemia; Peripheral Vascular Diseases; Chronic Limb-Threatening Ischemia

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Peripheral Arterial Disease; Atherosclerosis; Arteriosclerosis; Chronic Disease; Disease Attributes

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2012
• First Posted: March 8, 2012
• Study Start: March 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: January 22, 2020

Record last verified: 2020-01

Locations

CN (9)