A Phase IIB Pilot Study of a Modified Dosage Regimen of AMG0001 in Subjects With Critical Limb Ischemia

Phase 2CompletedNCT02016755

AnGes USA, Inc.10 enrolled

Overview

The purpose of the study is to confirm the feasibility of study procedures and the tolerability of a new dose regimen of AMG0001 in subjects with Critical Limb Ischemia (CLI)

The primary objectives of the study are: 1. To confirm the feasibility of study-related activities and the tolerability of a modified dosage regimen of AMG0001 in CLI 2. To evaluate safety of AMG0001

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Critical Limb Ischemia Vascular Diseases Peripheral Arterial Disease

Interventions

HGF PlasmidBIOLOGICAL

Intramuscular injection in the affected limb.

Eligibility

Sex: ALLMin age: 40 YearsMax age: 90 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Subjects with stable CLI (Severe Rutherford 4 and Rutherford 5) who have no option for revascularization by endovascular intervention or surgical bypass or a poor option (high risk) for revascularization by surgery and no option for an endovascular intervention * Subjects 40-90 years of either gender who have signed an informed consent * Subjects currently are taking a statin and an anti-platelet agent * If female, the subjects must not be of child bearing potential, e.g., post-menopausal or surgically sterile. * If a male subject is of reproductive potential, he must agree to use an accepted and effective (barrier) form of birth control starting with the first dose of study product and continue for 12 weeks from the last dose of study product. * Subjects with a previous medical history of myocardial infarction and/or stroke should have adequate management of risk factors to prevent secondary occurrence. * Subjects should have the ability to understand the requirements of the protocol and agree to return for the required study visits and assessments Exclusion Criteria: * Subjects whose CLI status is unstable (spontaneous marked improvement or marked worsening during the screening period). * Subjects who may require a major amputation (amputation at or above the ankle) within 4 weeks of Day 0 (± 4 weeks of Day 0). * Subjects with ulcers with exposure of tendons, osteomyelitis or uncontrolled infection or with the largest ulcer that is greater than 20 cm2 in area (\>10 cm2 area if on the heel). * Subjects with purely neuropathic or venous ulcers. * Subjects in Rutherford 6 class. * Subjects who have had revascularization by surgery or angioplasty within 3 months, unless the procedure has failed based on the anatomy or the hemodynamic measurements. * Subjects with a diagnosis of Buerger's disease (Thrombo-angiitis Obliterans). * Subjects currently receiving immunosuppressive, chemo or radiation therapy. * Evidence or history of malignant neoplasm (clinical, laboratory or imaging) except for successfully excised basal cell or squamous cell carcinoma, or successfully excised early melanoma of the skin. Subjects, who had successful tumor resection or radio-chemotherapy of breast cancer more than 10 years prior to inclusion in the study, and with no recurrence, may be enrolled in the study. Subjects, who had successful tumor resection or radio-chemotherapy of all other tumor types and have been in remission for more than 5 years prior to inclusion in the study, and with no recurrence, may be enrolled in the study. A dermatological exam will have ruled out any skin cancer. * Subjects who have proliferative retinopathy, or moderate or severe non-proliferative retinopathy, from any cause (ETDRS Score \> 35), clinically significant macular oedema or previous panretinal photocoagulation therapy. * Subjects with severe renal disease defined as significant renal dysfunction evidenced by an estimated creatinine clearance of \<30 mL/minute (calculated using the Cockcroft Gault formula), or receiving chronic hemodialysis therapy. * A Stroke, TIA or MI within 3 months of entry into the study. * Subjects with known liver disease (e.g., hepatitis B or C or cirrhosis of the liver). * A subject with HIV, AIDS, or severe uncontrolled ulcerative colitis or Crohn's disease. * Subjects with a current, uncorrected history of alcohol or substance abuse. * Subjects that have been administered rhPDGF (e.g, becaplermin) or other growth factors locally within one month of randomization. * Subjects who have received another investigational drug within 30 days of randomization or have previously received any gene transfer therapy within 3 years of entering the study.

Locations (1)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Outcomes

Primary Outcomes

Number of Participants With Adverse Events (AEs) Suspected to be Related to Injections of AMG0001

All summaries and analyses will be presented in tabular or graphical form. The study is not powered for the statistical inference and the test will be considered to be descriptive. Treatment-emergent adverse events (TEAEs) was evaluated, and a table showing the number and percentage of subjects with occurrences categorized by System Organ Class and Preferred Term was provided by causality (relationship to study drug).

Time frame: 18 months

Number of Participants Discontinued Due to AEs From the Injections of AMG0001

All summaries and analyses will be presented in tabular or graphical form. The study is not powered for the statistical inference and the test will be considered to be descriptive. Treatment-emergent adverse events (TEAEs) was evaluated, and a table showing the number and percentage of subjects with occurrences categorized by System Organ Class and Preferred Term was provided by whether the AE led to discontinuation.

Time frame: up to 18 Months

Secondary Outcomes

Number of Participants in Whom the Largest Ulcer Healed Completely or Gets Smaller (Photo Confirmation)

All summaries and analyses will be presented in tabular or graphical form. The study is not powered for the statistical inference and the test will be considered to be descriptive. A table showing the number of subjects completely healed in the target ulcer was provided at up to 6 months, \> 6 months to 12 months, from \>12 months to 18 months.

Time frame: 18 Months

Number of Participants in Whom Rest Pain (Based on 10 cm VAS Scale) Reduces by 20 mm (2 cm) or More or Was Completely Relieved.

All summaries and analyses will be presented in tabular or graphical form. The study is not powered for the statistical inference and the test will be considered to be descriptive. The severity of rest pain (based on the average over previous 7 days) recorded using the 10 cm visual analog scale (VAS). VAS is a 10-cm line (with score ranges 0 to 10), oriented horizontally; the left end of the line (0 mark) indicates "no pain"; the right end indicates "pain as bad as it can be." 1. The subject is asked to mark a place on the line corresponding to the average pain intensity experienced in the last 7 days. 2. The distance along the scale is converted into a numeric reading by measuring the distance of the subjects mark in cm from the beginning of the scale (the 0 mark).

Data from ClinicalTrials.gov

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