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| ID | Type | Description | Link |
|---|---|---|---|
| 2009-011998-32 | EudraCT Number |
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The purpose of this study is to evaluate the safety of two doses of PVS-10200, an allogeneic cellular therapy, delivered as a single injection following percutaneous transluminal ("balloon") angioplasty and stent placement for the treatment of peripheral artery disease (PAD).
This is an open-label dose escalation safety study of PVS-10200 in 30 subjects with peripheral artery disease (PAD) requiring balloon angioplasty and stent placement in the superficial femoral artery (SFA). The study will be completed sequentially in two dose cohorts of 10 subjects (low dose group, Cohort A) and 20 subjects (high dose group, Cohort B). A Data Safety Monitoring Board (DSMB) will conduct regular safety reviews.
Each subject will receive one treatment of PVS-10200 delivered by ultrasound guided injection to the perivascular region (external to the vessel) of the stented target lesion. The treatment will be administered within 24 hours after balloon angioplasty/stent placement.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PVS-10200 | Other | Each subject will receive one treatment of PVS-10200 delivered by ultrasound guided injection perivascular to the region of the target lesion within 24 hours of the completed angioplasty and stent placement. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PVS-10200 | Biological | PVS-10200 is composed of allogeneic human aortic endothelial cells cultured in a gelatin matrix. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Major Adverse Events (MAEs) | Major Adverse Events are: - Death - Major amputation - Procedural related serious adverse events - Investigational product related serious adverse events | within 4 weeks after study procedure |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Major Adverse Events (MAEs) | Major Adverse Events are: - Death - Major amputation - Procedural related serious adverse events - Investigational product related serious adverse events | within 24 and 48 weeks from study procedure |
| Incidence of Serious Adverse Events |
Not provided
Inclusion Criteria:
The subject has signed the informed consent document and patient information leaflet.
Male and female subject ≥ 18 years of age at the time of consent.
If female, the subject is (a) at least 1 year post-menopausal, or (b) surgically sterile, or (c) of child-bearing potential, with a negative serum pregnancy test result prior to study enrollment, who agrees to use adequate contraception for 6 months. Adequate contraception is defined as abstinence or a reliable method of birth control (e.g., a hormonal contraceptive, intra-uterine device, implantable or injectable contraceptives (Norplant® or Depo-Provera®), diaphragm, or condom with spermicide).
Subject has symptomatic peripheral arterial disease involving the superficial femoral artery, defined as Fontaine Class IIb, III and IV.
Meets anatomic requirements based on biplane digital subtraction angiography performed at the time of intervention including:
Target lesion is 7-15 cm in length.
Subject is expected to stay in the same geographic area for at least 48 weeks.
In the opinion of the investigator, the subject is able to understand and is willing to complete the study requirements.
Subject is receiving a therapeutic dose of statin therapy (starting minimum of 7 days prior to intervention) and continuing for a minimum of 4 weeks post-intervention.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre Hospitalier Universitaire d'Amiens | Amiens | France | ||||
| Hopital Europeen Georges Pompidou |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24613691 | Derived | Sevestre MA, Larghero J, Castier Y, Nugent HM, Visonneau S, Alsac JM. Pilot safety study of perivascular injection of tissue-engineered allogeneic aortic endothelial cells in patients undergoing minimally invasive peripheral revascularization. J Vasc Surg. 2014 Jun;59(6):1597-606. doi: 10.1016/j.jvs.2014.01.014. Epub 2014 Mar 7. |
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The study period was from 30 March 2010 (first patient's screening visit) to 19 June 2012 (last patient's Week 48 visit). A total of 30 subjects were screened for study eligibility, of whom a total of 21 subjects were registered (i.e., enrolled) and treated with PVS-10200. The study was conducted at 3 study centers in France
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| ID | Title | Description |
|---|---|---|
| FG000 | Low Dose PVS-10200 (Cohort A) | Low dose PVS-10200 (6×10^5 cells/cm lesion) |
| FG001 | High Dose PVS-10200 (Cohort B) | High dose PVS-10200 (15×10^5 cells/cm lesion) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort A | Low dose PVS-10200 (6×10^5 cells/cm lesion) |
| BG001 | Cohort B | High dose PVS-10200 (15×10^5 cells/cm lesion) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age at Screening |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Incidence of Major Adverse Events (MAEs) | Major Adverse Events are: - Death - Major amputation - Procedural related serious adverse events - Investigational product related serious adverse events | Intention-to-Treat Population Analysis | Posted | Number | participants | within 4 weeks after study procedure |
|
30 March 2010 (first patient's screening visit) to 19 June 2012 (last patient's Week 48 visit)
No increase in humoral sensitization seen after PVS-10200 treatment. Positive panel-reactive antibodies (PRA) findings seen at Wk 48 only in 2 subjects who also had positive PRA findings at Screening (i.e., sensitized prior to PVS 10-200 exposure). No treatment-emergent Adverse Events associated with humoral sensitization seen in either subject.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort A | Low dose PVS-10200 (6×10^5 cells/cm lesion) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ANGIOPLASTY | Surgical and medical procedures | MedDRA (12.0) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arterial Restenosis | Injury, poisoning and procedural complications | MedDRA (12.0) |
Small patient number, no control arm
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
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| ID | Term |
|---|---|
| D058729 | Peripheral Arterial Disease |
| ID | Term |
|---|---|
| D050197 | Atherosclerosis |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
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| Up to 48 weeks from study procedure |
| Incidence of Adverse Events, Laboratory Abnormalities | Up to 48 weeks from study procedure |
| Maintenance of Primary Patency of Superficial Femoral Artery (SFA) | Primary patency was defined as duplex ultrasound peak systolic velocity [PSV] ratio ≤2.4.Ultrasound data was obtained for each patient at each time point and had to be considered diagnostic and evaluable by the core lab; if it was not, then this analysis could not be done for that particular subject. | within 4 weeks from study procedure |
| Maintenance of Primary Patency of Superficial Femoral Artery (SFA) | Primary patency was defined as duplex ultrasound peak systolic velocity [PSV] ratio ≤2.4.Ultrasound data was obtained for each patient at each time point and had to be considered diagnostic and evaluable by the core lab; if it was not, then this analysis could not be done for that particular subject. | within 24 weeks from study procedure |
| Maintenance of Primary Patency of Superficial Femoral Artery (SFA) | Primary patency was defined as duplex ultrasound peak systolic velocity [PSV] ratio ≤2.4.Ultrasound data was obtained for each patient at each time point and had to be considered diagnostic and evaluable by the core lab; if it was not, then this analysis could not be done for that particular subject. | within 48 weeks from study procedure |
| Rate of Binary In-stent Restenosis | Binary restenosis relied on duplex ultrasound data with a Yes/No assessment with 0-49% being No (peak systolic velocity [PSV] ratio ≤2.4) and Yes being 50-99% (PSV ratio >2.4), with the PSV ratio calculated as PSV from stenosis divided by the PSV from a normal segment of artery proximal to the stenosis. Ultrasound data was obtained for each patient at each time point and had to be considered diagnostic and evaluable by the core lab; if it was not, then this analysis could not be done for that particular subject. | within 4 weeks from study procedure |
| Rate of Binary In-stent Restenosis | Binary restenosis relied on duplex ultrasound data with a Yes/No assessment with 0-49% being No (peak systolic velocity [PSV] ratio ≤2.4) and Yes being 50-99% (PSV ratio >2.4), with the PSV ratio calculated as PSV from stenosis divided by the PSV from a normal segment of artery proximal to the stenosis. Ultrasound data was obtained for each patient at each time point and had to be considered diagnostic and evaluable by the core lab; if it was not, then this analysis could not be done for that particular subject. | within 24 weeks from study procedure |
| Rate of Binary In-stent Restenosis | Binary restenosis relied on duplex ultrasound data with a Yes/No assessment with 0-49% being No (peak systolic velocity [PSV] ratio ≤2.4) and Yes being 50-99% (PSV ratio >2.4), with the PSV ratio calculated as PSV from stenosis divided by the PSV from a normal segment of artery proximal to the stenosis. Ultrasound data was obtained for each patient at each time point and had to be considered diagnostic and evaluable by the core lab; if it was not, then this analysis could not be done for that particular subject. | within 48 weeks from study procedure |
| Number of Patients Requiring Reintervention of Target Lesion / Target Vessel | Survival analysis - outcome reported as patients requiring reintervention of the target lesion / vessel | up to 48 Weeks from study procedure |
| Resting Ankle-brachial Index | ABI was calculated by dividing the systolic blood pressure at the ankle by the systolic blood pressures in the arm. This test is used to predict the severity of PAD. | within 4, 24 and 48 weeks from study procedure |
| Changes in Physical Exam | Changes in physical examination were compared to baseline: numbers of subjects presenting any new finding or worsening of abnormal findings compared to the screening examination are reported | within 4, 24 and 48 weeks from baseline |
| The Fontaine Class of Peripheral Artery Disease | CLASSIFICATION OF PERIPHERAL ATERIAL DISEASE ACCORDING TO FONTAINE Stage Clinical description I Asymptomatic IIA Mild claudication IIB Moderate -severe claudication III Ischemic rest pain IV Ulceration or gangrene | change from baseline to 4 weeks |
| The Fontaine Class of Peripheral Artery Disease | CLASSIFICATION OF PERIPHERAL ATERIAL DISEASE ACCORDING TO FONTAINE Stage Clinical description I Asymptomatic IIA Mild claudication IIB Moderate -severe claudication III Ischemic rest pain IV Ulceration or gangrene | change from baseline to 24 weeks |
| The Fontaine Class of Peripheral Artery Disease | CLASSIFICATION OF PERIPHERAL ATERIAL DISEASE ACCORDING TO FONTAINE Stage Clinical description I Asymptomatic IIA Mild claudication IIB Moderate -severe claudication III Ischemic rest pain IV Ulceration or gangrene | change from baseline to 48 weeks |
| Paris |
| 75015 |
| France |
| Hopital Bichat | Paris | 75018 | France |
| BG002 | Total | Total of all reporting groups |
| Standard Deviation |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Resting Ankle Brachial Index, Leg with Target Lesion | Mean | Standard Deviation | ratio |
|
| Fontaine Classification | Count of Participants | Participants |
|
| Units | Counts |
|---|
| Participants |
|
|
| Secondary | Incidence of Major Adverse Events (MAEs) | Major Adverse Events are: - Death - Major amputation - Procedural related serious adverse events - Investigational product related serious adverse events | Intention-to-Treat Population Analysis | Posted | Number | participants | within 24 and 48 weeks from study procedure |
|
|
|
| Secondary | Incidence of Serious Adverse Events | Intention-to-Treat Population Analysis | Posted | Number | participants | Up to 48 weeks from study procedure |
|
|
|
| Secondary | Incidence of Adverse Events, Laboratory Abnormalities | Safety Population Analysis | Posted | Number | participants | Up to 48 weeks from study procedure |
|
|
|
| Secondary | Maintenance of Primary Patency of Superficial Femoral Artery (SFA) | Primary patency was defined as duplex ultrasound peak systolic velocity [PSV] ratio ≤2.4.Ultrasound data was obtained for each patient at each time point and had to be considered diagnostic and evaluable by the core lab; if it was not, then this analysis could not be done for that particular subject. | Intention-to-Treat Population Analysis (Data was not available for all 21 subjects because it includes only ultrasound data obtained that was considered diagnostic and evaluable by the core lab) | Posted | Number | participants | within 4 weeks from study procedure |
|
|
|
| Secondary | Maintenance of Primary Patency of Superficial Femoral Artery (SFA) | Primary patency was defined as duplex ultrasound peak systolic velocity [PSV] ratio ≤2.4.Ultrasound data was obtained for each patient at each time point and had to be considered diagnostic and evaluable by the core lab; if it was not, then this analysis could not be done for that particular subject. | Intention-to-Treat Population Analysis (Data was not available for all 21 subjects because it includes only ultrasound data obtained that was considered diagnostic and evaluable by the core lab) | Posted | Number | participants | within 24 weeks from study procedure |
|
|
|
| Secondary | Maintenance of Primary Patency of Superficial Femoral Artery (SFA) | Primary patency was defined as duplex ultrasound peak systolic velocity [PSV] ratio ≤2.4.Ultrasound data was obtained for each patient at each time point and had to be considered diagnostic and evaluable by the core lab; if it was not, then this analysis could not be done for that particular subject. | Intention-to-Treat Population Analysis (Data was not available for all 21 subjects because it includes only ultrasound data obtained that was considered diagnostic and evaluable by the core lab) | Posted | Number | participants | within 48 weeks from study procedure |
|
|
|
| Secondary | Rate of Binary In-stent Restenosis | Binary restenosis relied on duplex ultrasound data with a Yes/No assessment with 0-49% being No (peak systolic velocity [PSV] ratio ≤2.4) and Yes being 50-99% (PSV ratio >2.4), with the PSV ratio calculated as PSV from stenosis divided by the PSV from a normal segment of artery proximal to the stenosis. Ultrasound data was obtained for each patient at each time point and had to be considered diagnostic and evaluable by the core lab; if it was not, then this analysis could not be done for that particular subject. | Intention-to-Treat Population Analysis (Data was not available for all 21 subjects because it includes only ultrasound data obtained that was considered diagnostic and evaluable by the core lab) | Posted | Number | participants | within 4 weeks from study procedure |
|
|
|
| Secondary | Rate of Binary In-stent Restenosis | Binary restenosis relied on duplex ultrasound data with a Yes/No assessment with 0-49% being No (peak systolic velocity [PSV] ratio ≤2.4) and Yes being 50-99% (PSV ratio >2.4), with the PSV ratio calculated as PSV from stenosis divided by the PSV from a normal segment of artery proximal to the stenosis. Ultrasound data was obtained for each patient at each time point and had to be considered diagnostic and evaluable by the core lab; if it was not, then this analysis could not be done for that particular subject. | Intention-to-Treat Population Analysis (Data was not available for all 21 subjects because it includes only ultrasound data obtained that was considered diagnostic and evaluable by the core lab) | Posted | Number | participants | within 24 weeks from study procedure |
|
|
|
| Secondary | Rate of Binary In-stent Restenosis | Binary restenosis relied on duplex ultrasound data with a Yes/No assessment with 0-49% being No (peak systolic velocity [PSV] ratio ≤2.4) and Yes being 50-99% (PSV ratio >2.4), with the PSV ratio calculated as PSV from stenosis divided by the PSV from a normal segment of artery proximal to the stenosis. Ultrasound data was obtained for each patient at each time point and had to be considered diagnostic and evaluable by the core lab; if it was not, then this analysis could not be done for that particular subject. | Intention-to-Treat Population Analysis (Data was not available for all 21 subjects because it includes only ultrasound data obtained that was considered diagnostic and evaluable by the core lab) | Posted | Number | participants | within 48 weeks from study procedure |
|
|
|
| Secondary | Number of Patients Requiring Reintervention of Target Lesion / Target Vessel | Survival analysis - outcome reported as patients requiring reintervention of the target lesion / vessel | Intention-to-Treat Population Analysis | Posted | Number | participants | up to 48 Weeks from study procedure |
|
|
|
| Secondary | Resting Ankle-brachial Index | ABI was calculated by dividing the systolic blood pressure at the ankle by the systolic blood pressures in the arm. This test is used to predict the severity of PAD. | Intention-to-Treat Population Analysis | Posted | Mean | Standard Deviation | ratio | within 4, 24 and 48 weeks from study procedure |
|
|
|
| Secondary | Changes in Physical Exam | Changes in physical examination were compared to baseline: numbers of subjects presenting any new finding or worsening of abnormal findings compared to the screening examination are reported | Safety Population Analysis | Posted | Number | participants | within 4, 24 and 48 weeks from baseline |
|
|
|
| Secondary | The Fontaine Class of Peripheral Artery Disease | CLASSIFICATION OF PERIPHERAL ATERIAL DISEASE ACCORDING TO FONTAINE Stage Clinical description I Asymptomatic IIA Mild claudication IIB Moderate -severe claudication III Ischemic rest pain IV Ulceration or gangrene | Intention-to-Treat Population Analysis | Posted | Number | participants | change from baseline to 4 weeks |
|
|
|
| Secondary | The Fontaine Class of Peripheral Artery Disease | CLASSIFICATION OF PERIPHERAL ATERIAL DISEASE ACCORDING TO FONTAINE Stage Clinical description I Asymptomatic IIA Mild claudication IIB Moderate -severe claudication III Ischemic rest pain IV Ulceration or gangrene | Intention-to-Treat Population Analysis | Posted | Number | participants | change from baseline to 24 weeks |
|
|
|
| Secondary | The Fontaine Class of Peripheral Artery Disease | CLASSIFICATION OF PERIPHERAL ATERIAL DISEASE ACCORDING TO FONTAINE Stage Clinical description I Asymptomatic IIA Mild claudication IIB Moderate -severe claudication III Ischemic rest pain IV Ulceration or gangrene | Intention-to-Treat Population Analysis | Posted | Number | participants | change from baseline to 48 weeks |
|
|
|
| 7 |
| 11 |
| 11 |
| 11 |
| EG001 | Cohort B | High dose PVS-10200 (15×10^5 cells/cm lesion) | 7 | 10 | 10 | 10 |
| ARTERIAL RESTENOSIS | Injury, poisoning and procedural complications | MedDRA (12.0) |
|
| ARTERIAL STENOSIS | Vascular disorders | MedDRA (12.0) |
|
| ERYSIPELAS | Infections and infestations | MedDRA (12.0) |
|
| FEMORAL ARTERY OCCLUSION | Vascular disorders | MedDRA (12.0) |
|
| IN-STENT ARTERIAL RESTENOSIS | Injury, poisoning and procedural complications | MedDRA (12.0) |
|
| INTERMITTENT CLAUDICATION | Vascular disorders | MedDRA (12.0) |
|
| LEG AMPUTATION | Surgical and medical procedures | MedDRA (12.0) |
|
| PANCREATITIS ACUTE | Gastrointestinal disorders | MedDRA (12.0) |
|
| PERIPHERAL ARTERY ANGIOPLASTY | Surgical and medical procedures | MedDRA (12.0) |
|
| PYELONEPHRITIS | Infections and infestations | MedDRA (12.0) |
|
| TOE AMPUTATION | Surgical and medical procedures | MedDRA (12.0) |
|
| WOUND NECROSIS | General disorders | MedDRA (12.0) |
|
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA (12.0) |
|
| Hypertension | Vascular disorders | MedDRA (12.0) |
|
| In-Stent Arterial Restenosis | Injury, poisoning and procedural complications | MedDRA (12.0) |
|
| Injection Site Haemorrhage | General disorders | MedDRA (12.0) |
|
| Intermittent Claudication | Vascular disorders | MedDRA (12.0) |
|
| Toe Amputation | Surgical and medical procedures | MedDRA (12.0) |
|
Company-specific confidentiality agreement
| D002318 |
| Cardiovascular Diseases |
| D016491 | Peripheral Vascular Diseases |
| Week 48 |
|
| Week 48 |
|
| STAGE IV (Baseline) to STAGE I (Week 4) |
|
| STAGE IV (Baseline) to STAGE IV (Week 4) |
|
| STAGE IIB (Baseline) to STAGE IIB (Week 24) |
|
| STAGE IV (Baseline) to STAGE I (Week 24) |
|
| STAGE IV (Baseline) to STAGE IV (Week 24) |
|
| Missing |
|
| STAGE IIB (Baseline) to STAGE IIB (Week 48) |
|
| STAGE IV (Baseline) to STAGE I (Week 48) |
|
| STAGE IV (Baseline) to STAGE IIB (Week 48) |
|
| STAGE IV (Baseline) to STAGE IV (Week 48) |
|
| Missing |
|