Study of PVS-10200 for the Treatment of Restenosis in Patients With Peripheral Artery Disease (TRIUMPH)
Study Details
Study Description
Brief Summary
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: PVS-10200 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. |
Biological: PVS-10200
PVS-10200 is composed of allogeneic human aortic endothelial cells cultured in a gelatin matrix.
|
Outcome Measures
Primary Outcome Measures
- Incidence of Major Adverse Events (MAEs) [within 4 weeks after study procedure]
Major Adverse Events are: - Death - Major amputation - Procedural related serious adverse events - Investigational product related serious adverse events
Secondary Outcome Measures
- Incidence of Major Adverse Events (MAEs) [within 24 and 48 weeks from study procedure]
Major Adverse Events are: - Death - Major amputation - Procedural related serious adverse events - Investigational product related serious adverse events
- Incidence of Serious Adverse Events [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) [within 4 weeks from study procedure]
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.
- Maintenance of Primary Patency of Superficial Femoral Artery (SFA) [within 24 weeks from study procedure]
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.
- Maintenance of Primary Patency of Superficial Femoral Artery (SFA) [within 48 weeks from study procedure]
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.
- Rate of Binary In-stent Restenosis [within 4 weeks from study procedure]
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.
- Rate of Binary In-stent Restenosis [within 24 weeks from study procedure]
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.
- Rate of Binary In-stent Restenosis [within 48 weeks from study procedure]
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.
- Number of Patients Requiring Reintervention of Target Lesion / Target Vessel [up to 48 Weeks from study procedure]
Survival analysis - outcome reported as patients requiring reintervention of the target lesion / vessel
- Resting Ankle-brachial Index [within 4, 24 and 48 weeks from study procedure]
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.
- Changes in Physical Exam [within 4, 24 and 48 weeks from baseline]
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
- The Fontaine Class of Peripheral Artery Disease [change from baseline to 4 weeks]
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
- The Fontaine Class of Peripheral Artery Disease [change from baseline to 24 weeks]
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
- The Fontaine Class of Peripheral Artery Disease [change from baseline to 48 weeks]
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
Eligibility Criteria
Criteria
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:
-
Stenosis of ≥ 50% or occlusion of the superficial femoral artery, and
-
Target lesion length of ≤ 150 mm, and
-
At least one patent (< 50 % stenosis) tibioperoneal runoff vessel
-
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:
-
Subject has acute limb ischemia.
-
Subject has had prior revascularization of the target lesion.
-
Subject has untreated inflow disease of the ipsilateral pelvic arteries (> 50% stenosis or occlusion).
-
The target lesion is located within an aneurysm or associated with an aneurysm in the vessel segment either proximal or distal to the target lesion(s).
-
Subject has an unresolved thrombus within the target vessel.
-
Additional percutaneous interventional procedures (cardiac/peripheral) are planned ≤ 30 days following the study procedure.
-
Subject has suffered a hemorrhagic stroke ≤ 6 mo prior to the study procedure.
-
Subject has a history of bleeding diatheses or coagulopathy.
-
Subject is diagnosed with septicemia at the time of the study procedure.
-
Subject is known to be seropositive for HIV.
-
Subject has some other medical illness that may cause the subject to be non-compliant with the protocol.
-
Subject has a known allergy to bovine or porcine products (i.e., heparin).
-
Subject has a known allergy to collagen/gelatin products.
-
Subject has had a severe reaction to contrast media.
-
Subject has a known allergy or intolerance to anti-platelet medication (e.g., acetylsalicylic acid or clopidogrel) or statin therapy.
-
Subject has a history of IV drug use within 6 months prior to screening.
-
Subject has a documented diagnosis of cancer within 2 years (24 months) prior to screening.
-
Subject is a female who is pregnant, breast-feeding, or plans to become pregnant during the study.
-
Subject is currently participating in another investigational drug, biologic or device trial, plans to participate in another investigational drug, biologic or device study during participation in this study, or has completed participation in another investigational drug, biologic or device trial within the last 30 days. Note: Subjects involved in extended follow-up trials for products that are currently commercially available and used as approved are not considered to be participating investigational trials.
-
Subject is a staff member of any of the participating institutions or relative of a staff member.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Centre Hospitalier Universitaire d'Amiens | Amiens | France | ||
| 2 | Hopital Europeen Georges Pompidou | Paris | France | 75015 | |
| 3 | Hopital Bichat | Paris | France | 75018 |
Sponsors and Collaborators
- Shire
Investigators
- Study Director: Study Director, Takeda
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PVS 03-001
- 2009-011998-32
Study Results
Participant Flow
| Recruitment Details | 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 |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Low Dose PVS-10200 (Cohort A) | High Dose PVS-10200 (Cohort B) |
|---|---|---|
| Arm/Group Description | Low dose PVS-10200 (6×10^5 cells/cm lesion) | High dose PVS-10200 (15×10^5 cells/cm lesion) |
| Period Title: Overall Study | ||
| STARTED | 11 | 10 |
| COMPLETED | 10 | 9 |
| NOT COMPLETED | 1 | 1 |
Baseline Characteristics
| Arm/Group Title | Cohort A | Cohort B | Total |
|---|---|---|---|
| Arm/Group Description | Low dose PVS-10200 (6×10^5 cells/cm lesion) | High dose PVS-10200 (15×10^5 cells/cm lesion) | Total of all reporting groups |
| Overall Participants | 11 | 10 | 21 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
61.6
(10.11)
|
70.7
(7.67)
|
66.0
(9.96)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
2
18.2%
|
4
40%
|
6
28.6%
|
| Male |
9
81.8%
|
6
60%
|
15
71.4%
|
| Region of Enrollment (Count of Participants) | |||
| France |
11
100%
|
10
100%
|
21
100%
|
| Resting Ankle Brachial Index, Leg with Target Lesion (ratio) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [ratio] |
0.954
(0.164)
|
0.851
(0.258)
|
0.902
(0.217)
|
| Fontaine Classification (Count of Participants) | |||
| STAGE IIB-MODERATE TO SEVERE CLAUDICATION(<200M) |
10
90.9%
|
6
60%
|
16
76.2%
|
| STAGE IV - ULCERATION OR GANGRENE |
1
9.1%
|
4
40%
|
5
23.8%
|
Outcome Measures
| Title | Incidence of Major Adverse Events (MAEs) |
|---|---|
| Description | Major Adverse Events are: - Death - Major amputation - Procedural related serious adverse events - Investigational product related serious adverse events |
| Time Frame | within 4 weeks after study procedure |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat Population Analysis |
| Arm/Group Title | Cohort A | Cohort B |
|---|---|---|
| Arm/Group Description | Low dose PVS-10200 (6×10^5 cells/cm lesion) | High dose PVS-10200 (15×10^5 cells/cm lesion) |
| Measure Participants | 11 | 10 |
| Number [participants] |
0
0%
|
0
0%
|
| Title | Incidence of Major Adverse Events (MAEs) |
|---|---|
| Description | Major Adverse Events are: - Death - Major amputation - Procedural related serious adverse events - Investigational product related serious adverse events |
| Time Frame | within 24 and 48 weeks from study procedure |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat Population Analysis |
| Arm/Group Title | Cohort A | Cohort B |
|---|---|---|
| Arm/Group Description | Low dose PVS-10200 (6×10^5 cells/cm lesion) | High dose PVS-10200 (15×10^5 cells/cm lesion) |
| Measure Participants | 11 | 10 |
| Week 24 |
0
0%
|
0
0%
|
| Week 48 |
0
0%
|
1
10%
|
| Title | Incidence of Serious Adverse Events |
|---|---|
| Description | |
| Time Frame | Up to 48 weeks from study procedure |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat Population Analysis |
| Arm/Group Title | Cohort A | Cohort B |
|---|---|---|
| Arm/Group Description | Low dose PVS-10200 (6×10^5 cells/cm lesion) | High dose PVS-10200 (15×10^5 cells/cm lesion) |
| Measure Participants | 11 | 10 |
| Number [participants] |
7
63.6%
|
7
70%
|
| Title | Incidence of Adverse Events, Laboratory Abnormalities |
|---|---|
| Description | |
| Time Frame | Up to 48 weeks from study procedure |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population Analysis |
| Arm/Group Title | Cohort A | Cohort B |
|---|---|---|
| Arm/Group Description | Low dose PVS-10200 (6×10^5 cells/cm lesion) | High dose PVS-10200 (15×10^5 cells/cm lesion) |
| Measure Participants | 11 | 10 |
| Treatment Emergent Adverse Events |
11
100%
|
10
100%
|
| Clinically Significant Laboratory |
1
9.1%
|
5
50%
|
| Title | Maintenance of Primary Patency of Superficial Femoral Artery (SFA) |
|---|---|
| Description | 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. |
| Time Frame | within 4 weeks from study procedure |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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) |
| Arm/Group Title | Cohort A | Cohort B |
|---|---|---|
| Arm/Group Description | Low dose PVS-10200 (6×10^5 cells/cm lesion) | High dose PVS-10200 (15×10^5 cells/cm lesion) |
| Measure Participants | 11 | 10 |
| NO |
0
0%
|
0
0%
|
| YES |
9
81.8%
|
9
90%
|
| Title | Maintenance of Primary Patency of Superficial Femoral Artery (SFA) |
|---|---|
| Description | 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. |
| Time Frame | within 24 weeks from study procedure |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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) |
| Arm/Group Title | Cohort A | Cohort B |
|---|---|---|
| Arm/Group Description | Low dose PVS-10200 (6×10^5 cells/cm lesion) | High dose PVS-10200 (15×10^5 cells/cm lesion) |
| Measure Participants | 11 | 10 |
| NO |
4
36.4%
|
4
40%
|
| YES |
5
45.5%
|
4
40%
|
| Title | Maintenance of Primary Patency of Superficial Femoral Artery (SFA) |
|---|---|
| Description | 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. |
| Time Frame | within 48 weeks from study procedure |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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) |
| Arm/Group Title | Cohort A | Cohort B |
|---|---|---|
| Arm/Group Description | Low dose PVS-10200 (6×10^5 cells/cm lesion) | High dose PVS-10200 (15×10^5 cells/cm lesion) |
| Measure Participants | 11 | 10 |
| NO |
3
27.3%
|
3
30%
|
| YES |
4
36.4%
|
3
30%
|
| Title | Rate of Binary In-stent Restenosis |
|---|---|
| Description | 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. |
| Time Frame | within 4 weeks from study procedure |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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) |
| Arm/Group Title | Cohort A | Cohort B |
|---|---|---|
| Arm/Group Description | Low dose PVS-10200 (6×10^5 cells/cm lesion) | High dose PVS-10200 (15×10^5 cells/cm lesion) |
| Measure Participants | 11 | 10 |
| NO |
9
81.8%
|
9
90%
|
| YES |
0
0%
|
0
0%
|
| Title | Rate of Binary In-stent Restenosis |
|---|---|
| Description | 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. |
| Time Frame | within 24 weeks from study procedure |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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) |
| Arm/Group Title | Cohort A | Cohort B |
|---|---|---|
| Arm/Group Description | Low dose PVS-10200 (6×10^5 cells/cm lesion) | High dose PVS-10200 (15×10^5 cells/cm lesion) |
| Measure Participants | 11 | 10 |
| NO |
9
81.8%
|
8
80%
|
| YES |
0
0%
|
0
0%
|
| Title | Rate of Binary In-stent Restenosis |
|---|---|
| Description | 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. |
| Time Frame | within 48 weeks from study procedure |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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) |
| Arm/Group Title | Cohort A | Cohort B |
|---|---|---|
| Arm/Group Description | Low dose PVS-10200 (6×10^5 cells/cm lesion) | High dose PVS-10200 (15×10^5 cells/cm lesion) |
| Measure Participants | 11 | 10 |
| NO |
8
72.7%
|
7
70%
|
| YES |
0
0%
|
0
0%
|
| Title | Number of Patients Requiring Reintervention of Target Lesion / Target Vessel |
|---|---|
| Description | Survival analysis - outcome reported as patients requiring reintervention of the target lesion / vessel |
| Time Frame | up to 48 Weeks from study procedure |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat Population Analysis |
| Arm/Group Title | Cohort A | Cohort B |
|---|---|---|
| Arm/Group Description | Low dose PVS-10200 (6×10^5 cells/cm lesion) | High dose PVS-10200 (15×10^5 cells/cm lesion) |
| Measure Participants | 11 | 10 |
| Number [participants] |
4
(15.4%)
36.4%
|
2
(12.6%)
20%
|
| Title | Resting Ankle-brachial Index |
|---|---|
| Description | 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. |
| Time Frame | within 4, 24 and 48 weeks from study procedure |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat Population Analysis |
| Arm/Group Title | Cohort A | Cohort B |
|---|---|---|
| Arm/Group Description | Low dose PVS-10200 (6×10^5 cells/cm lesion) | High dose PVS-10200 (15×10^5 cells/cm lesion) |
| Measure Participants | 11 | 10 |
| Week 4 |
0.984
(0.128)
|
0.887
(0.237)
|
| Week 24 |
0.948
(0.172)
|
0.842
(0.204)
|
| Week 48 |
0.931
(0.193)
|
0.857
(0.226)
|
| Title | Changes in Physical Exam |
|---|---|
| Description | 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 |
| Time Frame | within 4, 24 and 48 weeks from baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population Analysis |
| Arm/Group Title | Cohort A | Cohort B |
|---|---|---|
| Arm/Group Description | Low dose PVS-10200 (6×10^5 cells/cm lesion) | High dose PVS-10200 (15×10^5 cells/cm lesion) |
| Measure Participants | 11 | 10 |
| Week 4 |
0
0%
|
3
30%
|
| Week 24 |
5
45.5%
|
1
10%
|
| Week 48 |
3
27.3%
|
3
30%
|
| Title | The Fontaine Class of Peripheral Artery Disease |
|---|---|
| Description | 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 |
| Time Frame | change from baseline to 4 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat Population Analysis |
| Arm/Group Title | Cohort A | Cohort B |
|---|---|---|
| Arm/Group Description | Low dose PVS-10200 (6×10^5 cells/cm lesion) | High dose PVS-10200 (15×10^5 cells/cm lesion) |
| Measure Participants | 11 | 10 |
| STAGE IIB (Baseline) to STAGE I (Week 4) |
9
81.8%
|
5
50%
|
| STAGE IIB (Baseline) to STAGE IIA (Week 4) |
1
9.1%
|
1
10%
|
| STAGE IV (Baseline) to STAGE I (Week 4) |
1
9.1%
|
0
0%
|
| STAGE IV (Baseline) to STAGE IV (Week 4) |
0
0%
|
4
40%
|
| Title | The Fontaine Class of Peripheral Artery Disease |
|---|---|
| Description | 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 |
| Time Frame | change from baseline to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat Population Analysis |
| Arm/Group Title | Cohort A | Cohort B |
|---|---|---|
| Arm/Group Description | Low dose PVS-10200 (6×10^5 cells/cm lesion) | High dose PVS-10200 (15×10^5 cells/cm lesion) |
| Measure Participants | 11 | 10 |
| STAGE IIB (Baseline) to STAGE I (Week 24) |
4
36.4%
|
3
30%
|
| STAGE IIB (Baseline) to STAGE IIA (Week 24) |
4
36.4%
|
1
10%
|
| STAGE IIB (Baseline) to STAGE IIB (Week 24) |
2
18.2%
|
1
10%
|
| STAGE IV (Baseline) to STAGE I (Week 24) |
0
0%
|
1
10%
|
| STAGE IV (Baseline) to STAGE IV (Week 24) |
0
0%
|
2
20%
|
| Missing |
1
9.1%
|
2
20%
|
| Title | The Fontaine Class of Peripheral Artery Disease |
|---|---|
| Description | 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 |
| Time Frame | change from baseline to 48 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat Population Analysis |
| Arm/Group Title | Cohort A | Cohort B |
|---|---|---|
| Arm/Group Description | Low dose PVS-10200 (6×10^5 cells/cm lesion) | High dose PVS-10200 (15×10^5 cells/cm lesion) |
| Measure Participants | 11 | 10 |
| STAGE IIB (Baseline) to STAGE I (Week 48) |
6
54.5%
|
4
40%
|
| STAGE IIB (Baseline) to STAGE IIA (Week 48) |
1
9.1%
|
1
10%
|
| STAGE IIB (Baseline) to STAGE IIB (Week 48) |
3
27.3%
|
1
10%
|
| STAGE IV (Baseline) to STAGE I (Week 48) |
0
0%
|
1
10%
|
| STAGE IV (Baseline) to STAGE IIB (Week 48) |
0
0%
|
1
10%
|
| STAGE IV (Baseline) to STAGE IV (Week 48) |
0
0%
|
1
10%
|
| Missing |
1
9.1%
|
1
10%
|
Adverse Events
| Time Frame | 30 March 2010 (first patient's screening visit) to 19 June 2012 (last patient's Week 48 visit) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | 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. | |||
| Arm/Group Title | Cohort A | Cohort B | ||
| Arm/Group Description | Low dose PVS-10200 (6×10^5 cells/cm lesion) | High dose PVS-10200 (15×10^5 cells/cm lesion) | ||
All Cause Mortality |
||||
| Cohort A | Cohort B | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Cohort A | Cohort B | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/11 (63.6%) | 7/10 (70%) | ||
| Gastrointestinal disorders | ||||
| PANCREATITIS ACUTE | 1/11 (9.1%) | 0/10 (0%) | ||
| General disorders | ||||
| WOUND NECROSIS | 0/11 (0%) | 1/10 (10%) | ||
| Infections and infestations | ||||
| ERYSIPELAS | 0/11 (0%) | 1/10 (10%) | ||
| PYELONEPHRITIS | 0/11 (0%) | 1/10 (10%) | ||
| Injury, poisoning and procedural complications | ||||
| ARTERIAL RESTENOSIS | 2/11 (18.2%) | 0/10 (0%) | ||
| IN-STENT ARTERIAL RESTENOSIS | 3/11 (27.3%) | 3/10 (30%) | ||
| Surgical and medical procedures | ||||
| ANGIOPLASTY | 1/11 (9.1%) | 0/10 (0%) | ||
| LEG AMPUTATION | 0/11 (0%) | 1/10 (10%) | ||
| PERIPHERAL ARTERY ANGIOPLASTY | 1/11 (9.1%) | 0/10 (0%) | ||
| TOE AMPUTATION | 0/11 (0%) | 2/10 (20%) | ||
| Vascular disorders | ||||
| ARTERIAL STENOSIS | 1/11 (9.1%) | 0/10 (0%) | ||
| FEMORAL ARTERY OCCLUSION | 0/11 (0%) | 1/10 (10%) | ||
| INTERMITTENT CLAUDICATION | 6/11 (54.5%) | 2/10 (20%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Cohort A | Cohort B | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/11 (100%) | 10/10 (100%) | ||
| General disorders | ||||
| Injection Site Haemorrhage | 2/11 (18.2%) | 0/10 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Arterial Restenosis | 2/11 (18.2%) | 0/10 (0%) | ||
| In-Stent Arterial Restenosis | 3/11 (27.3%) | 3/10 (30%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Ecchymosis | 1/11 (9.1%) | 3/10 (30%) | ||
| Surgical and medical procedures | ||||
| Toe Amputation | 0/11 (0%) | 2/10 (20%) | ||
| Vascular disorders | ||||
| Hypertension | 4/11 (36.4%) | 0/10 (0%) | ||
| Intermittent Claudication | 6/11 (54.5%) | 2/10 (20%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Company-specific confidentiality agreement
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Shire |
| Phone | +1 866 842 5335 |
| ClinicalTransparency@shire.com |
- PVS 03-001
- 2009-011998-32