Efficacy and Safety of AMG0001 in Subjects With Critical Limb Ischemia

NCT ID: NCT02144610

Last Updated: 2019-08-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-12
• Study Completion Date: 2016-11-28

Brief Summary

Study to Evaluate the Efficacy and Safety of AMG0001 in Subjects with Critical Limb Ischemia.

Detailed Description

This is a double-blind, randomized, placebo-controlled, phase 3, multinational, multicenter study of AMG0001 (HGF plasmid) in subjects with Critical Limb Ischemia (CLI).

Conditions

Critical Limb Ischemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Gene Therapy HGF Plasmid (AMG0001)

Randomized subjects will receive 4 sets of intramuscular (IM) injections of HGF plasmid two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.

Group Type: EXPERIMENTAL

HGF Plasmid (AMG0001)

Intervention Type: BIOLOGICAL

IM

Placebo

Randomized subjects will receive 4 sets of intramuscular (IM) injections of matching placebo two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.

Group Type: PLACEBO_COMPARATOR

Matching Placebo

Intervention Type: BIOLOGICAL

IM

Interventions

HGF Plasmid (AMG0001)

IM

Intervention Type: BIOLOGICAL

Matching Placebo

IM

Intervention Type: BIOLOGICAL

Other Intervention Names

Beperminogene perplasmid (INN)

Eligibility Criteria

Inclusion Criteria

1. Subjects with CLI (Severe Rutherford 4 and Rutherford 5) who have:

• No option for revascularization by endovascular intervention or surgical bypass

or

• Poor option (high risk) for revascularization by surgery and no option for an endovascular intervention (see Section 3.1 Study Population for full definition for appropriate inclusions).

2. Subjects 40-90 years of either gender who have signed an informed consent form either directly or through a legally authorized representative.

3. Subjects currently are taking a statin and an anti-platelet agent (e.g., clopidogrel, ticlopidine, aspirin, etc.) for 2 weeks or more prior to Day 0 as part of their standard of care, unless contraindicated. Subjects for whom these agents are contraindicated will have the reason for contraindication recorded in their case report form (CRF).

4. If female, the subjects must not be of child bearing potential, e.g., post-menopausal or surgically sterile.

5. 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. This applies to both courses of treatment.

6. Subjects with a previous medical history of myocardial infarction and/or stroke should have adequate management of risk factors to prevent secondary occurrence. (See Section 4.2 Medical History for guidelines on appropriate secondary prevention.)

7. Subjects should have the ability to understand the requirements of the protocol and agree to return for the required study visits, assessments and follow up.

• The index leg will be the leg with the greater severity of CLI disease. Entry requirements apply to the index leg. The index leg may also be referred to as the treated leg or affected leg in the text of this protocol or other study documents. If the subject has two legs that have the same Rutherford classification (severe Rutherford 4 or Rutherford 5) and are both eligible for treatment, the leg with greater disease severity (based on more extensive necrosis or more extensive/deeper ulceration(s), difference in ABI (ankle brachial index) or TBI (toe brachial index) ≥ 0.1, and/or more extensive vascular disease based on the angiogram) will be chosen as the index leg. If there is no clinical, hemodynamic or angiographic or other evidence to determine which leg has greater disease severity, the subject will be excluded from the study.
• These entry criteria will be enforced (prior to randomization) by the Sponsor, as well as an Entry Committee who will review all relevant clinical data including but not limited to medical illness, CLI status, the findings of an angiogram, ulcer photographs and measurements and hemodynamic data.

Exclusion Criteria

1. Subjects whose CLI status is unstable (spontaneous marked improvement or marked worsening during the screening period) or who have excessive tissue necrosis that is unlikely to benefit from medication, or those poor option subjects requiring immediate revascularization by surgery. Stability of the CLI status will be confirmed by the Principal Investigator prior to randomization and retrospectively reviewed by the Adjudication Committee.

2. Subjects who may require a major amputation (amputation at or above the ankle) within 4 weeks of Day 0 (± 4 weeks of Day 0).

3. 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).

4. Subjects with purely neuropathic, or with venous ulcers.

5. Subjects in Rutherford 6 class.

6. 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.

7. Subjects with a diagnosis of Buerger's disease (Thrombo-angiitis Obliterans).

8. Subjects currently receiving immunosuppressive, chemo or radiation therapy.

9. 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.

10. 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 (Results from the Early Treatment Diabetic Retinopathy Study. Ophthalmology May 1991 Supplement 98: 823-833).

11. Females of child-bearing potential defined as subjects that are not surgically sterile or post-menopausal.

12. 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.

13. Any co-morbid condition likely to interfere with assessment of safety or efficacy endpoints, acute cardiovascular events (i.e., CVA (cardiovascular accident), MI (myocardial infarction), etc.) within 3 months of treatment, or any disease that in the opinion of the Investigator may result in subject mortality in less than 3 months.

14. Subjects with known liver disease (e.g., hepatitis B or C or cirrhosis of the liver).

15. A subject with HIV, AIDS, severe uncontrolled inflammatory disease or severe uncontrolled autoimmune disease (e.g., ulcerative colitis, Crohn's disease, etc).

16. Subjects who have a significant psychiatric disorder or mental disability that could interfere with the subject's ability to provide informed consent or comply with study procedures.

17. Subjects with a current, uncorrected history of alcohol or substance abuse.

18. Diabetic subjects with an uncorrected HbA1c > 9.0% during the screening period.

19. Subjects that have been administered rhPDGF (e.g, becaplermin) or other growth factors locally within one month of randomization.

20. 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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AnGes USA, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard J. Powell, MD

Role: PRINCIPAL_INVESTIGATOR

Dartmouth-Hitchcock Medical Center

Locations

Carondelet Heart and Vascular Institute

Tucson, Arizona, United States

Central Arkansas Veteran's Healthcare System

Little Rock, Arkansas, United States

University of California, San Diego (UCSD)

La Jolla, California, United States

Alliance Research Centers

Laguna Hills, California, United States

San Francisco Veterans Affairs Medical Center

San Francisco, California, United States

University of Florida

Gainesville, Florida, United States

Sarasota Memorial Hospital Clinical Research Center

Sarasota, Florida, United States

Emory University

Atlanta, Georgia, United States

Harbin Clinic, LLC

Rome, Georgia, United States

Northwestern University

Chicago, Illinois, United States

Northwestern Medicine Central DuPage Hospital

Winfield, Illinois, United States

Peninsula Region Medical Center

Salisbury, Maryland, United States

Boston University School of Medicine

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Saint Luke's Hospital

Kansas City, Missouri, United States

Kansas City Vascular P.C.

Kansas City, Missouri, United States

Mercy Medical Research Institute

Springfield, Missouri, United States

Mercy Hospital St. Louis

St Louis, Missouri, United States

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Holy Name Medical Center

Teaneck, New Jersey, United States

New York Presbyterian Hospital - Columbia University Medical Center

New York, New York, United States

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

University of Oklahoma - Physicians Surgical Specialists

Tulsa, Oklahoma, United States

Oregon Health and Science University

Portland, Oregon, United States

Veterans Affairs Medical Center

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Sanford Health

Sioux Falls, South Dakota, United States

The Methodist Hospital Research Institute

Houston, Texas, United States

Antwerpen University Hospital

Edegem, , Belgium

Ziekenhuis Oost Limburg

Genk, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

Jewish General Hospital

Montreal, Quebec, Canada

Regionshospitalet Viborg

Viborg, , Denmark

Helsinki University Hospital

Helsinki, , Finland

Kuopio University Hospital

Kuopio, , Finland

Kuopio University Hospital

Kuopio, , Finland

Tampere University Hospital

Tampere, , Finland

Hopital Cardiologique - CHU Lille

Lille, Nord, France

CHU Amiens - Groupe Hospitalier Hopital Sud

Amiens, , France

Hôpital Saint André

Bordeaux, , France

CHU de Grenoble - Hôpital Albert Michallon

Grenoble, , France

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, , Hungary

Debreceni Egyetem Klinikai Kozpont, Belgyogyaszati Klinika

Debrecen, , Hungary

Petz Aladar Megyei Oktato Korhaz

Győr, , Hungary

Bekes Megyei Pandy Kalman Korhaz Ersebeszet

Gyula, , Hungary

Bekes Megyei Pandy Kalman Korhaz

Gyula, , Hungary

Somogy Megyei Kaposi Mor Oktato Korhaz Altalanos- Mellkas es Ersebeszeti Osztaly

Kaposvár, , Hungary

Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz

Miskolc, , Hungary

SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz

Nyíregyháza, , Hungary

Pecsi Tudomanyegyetem AOK

Pécs, , Hungary

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinika Központ

Szeged, , Hungary

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz

Székesfehérvár, , Hungary

Universita Cattolica Policlinico Gemelli

Roma, , Italy

Leiden Universitair Medisch Centrum

Leiden, , Netherlands

Maastricht University Medical Center

Maastricht, , Netherlands

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

Szpital Uniwersytecki nr 1 im. Dr A. Jurasza w Bydgoszczy

Bydgoszcz, , Poland

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego

Poznan, , Poland

Karlkirurgiska Kliniken, Karolinska Universitetssjukhuset

Stockholm, , Sweden

Countries

United States; Belgium; Canada; Denmark; Finland; France; Hungary; Italy; Netherlands; Poland; Sweden

Other Identifiers

2014-001129-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AG-CLI-0206

Identifier Type: -

Identifier Source: org_study_id