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Autologous BMMNC Combined With HA Therapy for PAOD

Primary Purpose

Peripheral Arterial Occlusive Disease, Critical Limb Ischemia

Status

Withdrawn

Phase

Phase 1

Locations

Taiwan

Study Type

Interventional

Intervention

RV-P1501

About this trial

This is an interventional treatment trial for Peripheral Arterial Occlusive Disease focused on measuring Hyaluronan, Bone marrow mononuclear cells

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patient age ≥ 20
Patients with severe PAOD and diagnosed with Rutherford category 3, 4, or 5
Contraindication to angioplasty or bypass surgery, or post-angioplasty or bypass surgery for once but with limited or no effect.
Patient without hypertension or hypertensive patient with adequate-controlled blood pressure.
With signed informed consent

Exclusion Criteria:

Patient undergone any organ transplantation
Inability to undergo bone marrow aspiration
Pregnant woman
Life expectancy < 1 year
Cognitive impairment
Active malignancy in 5 years prior to treatment
Bleeding diathesis or pulmonary embolism
Patient with active major cardiovascular diseases such as unstable angina, arrhythmia, heart failure, impaired cardiac function (ejection fraction < 45%), or stroke
Estimated Glomerular Filtration Rate (eGFR) < 30
Glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) values higher than 80 U/L
Patient with severe diabetes mellitus (HbA1C > 8%)
Patient with alcohol addiction
Patient with drug abuse
Patient with infections or skin disease on the ischemic leg.
Allergic to HA
Patient whose blockage region only occurred in the femoral artery or at foot.

Sites / Locations

National Cheng Kung University Hospital
National Taiwan University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

RV-P1501-4

RV-P1501-5

RV-P1501-6

Arm Description

Gel-like product with 10 thousand BMMNCs in each ml of 1% hyaluronan (HA) solution

Gel-like product with 100 thousand BMMNCs in each ml of 1% hyaluronan (HA) solution

Gel-like product with 1 million BMMNCs in each ml of 1% hyaluronan (HA) solution

Outcomes

Primary Outcome Measures

Ankle Brachial Index (ABI)

The percentage change of ABI from 3 follow-ups with the baseline.

Secondary Outcome Measures

Clinical status (Rutherford category)

Improvement in Rutherford scale was recorded at baseline and each follow-up.

Level of pain at rest

Rest pain was measured using Wong-Baker FACES pain rating scale at baseline and each follow-up visit.

Ulcer size in cm2

Ulcer size was assessed and measured at each follow-up interval and compared to baseline.

Ulcer category

Ulcer status was assessed at each follow-up interval and compared to baseline.

PWT/PFWT in seconds

Peak walking time and pain-free walking time was measured at baseline and compared to W4, W12 and W24 by treadmill walking tests.

Amputation free

Time to below the knee amputation of the ipsilateral leg after the treatment.

Ejection fraction

Ejection fraction was measured by echocardiogram to record the cardiac function at W12 and W24.

CT angiography

CT angiography was performed to record the morphology of blood vessel, location, and the vessel cross section percentage.

Biochemistry

Biochemistry tests were performed to interpret the health assessment at W12 and W24.

Hematology

Hematology tests were performed to interpret the health assessment at W12 and W24.

Full Information

NCT ID

NCT03214887

First Posted

July 5, 2017

Last Updated

March 1, 2022

Sponsor

Academia Sinica, Taiwan

Collaborators

National Taiwan University Hospital, National Cheng-Kung University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03214887

Brief Title

Autologous BMMNC Combined With HA Therapy for PAOD

Official Title

Therapeutic Angiogenesis for Peripheral Artery Occlusive Disease Using Hyaluronan Combined With Autologous Bone Marrow Cell Therapy -- Phase I/II Safety and Efficacy Study

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Withdrawn

Why Stopped

Incomplete enrollment process

Study Start Date

January 17, 2017 (Actual)

Primary Completion Date

June 30, 2018 (Anticipated)

Study Completion Date

July 27, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Academia Sinica, Taiwan

Collaborators

National Taiwan University Hospital, National Cheng-Kung University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of hyaluronan combined with autologous bone marrow mononuclear cells for the treatment of critical PAOD patients.

Detailed Description

This is a multicenter, non-blinded and randomized study to evaluate the safety and efficacy of hyaluronan (HA) combined with autologous bone marrow mononuclear cells (BMMNC) therapy for critical peripheral arterial occlusive disease (PAOD) patients. A total of 30 subjects will be recruited into the study. The subjects will be randomized into 3 different arms. During the Phase I study, 9 subjects recruited while another 21 additional subjects will be recruited in Phase II after the review of DSMB and consultation of Taiwan FDA on the results of the Phase I study. Each subject will be administered 5~10 injections of RV-P1501, the number of injections depends on the size of the subject's ischemic leg. Each subject will receive treatment once. Subjects will be assigned to the treatments in random order. Evaluations including ABI, PWT/PFWT, clinical status, EF, CTA, biochemistry and hematology checked during the inclusion and exclusion evaluation, and will be taken at baseline, 1 week, 2 weeks, 4 weeks, 12 weeks, and 24 weeks after the treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Peripheral Arterial Occlusive Disease, Critical Limb Ischemia

Keywords

Hyaluronan, Bone marrow mononuclear cells

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Model Description

RV-P1501-4: Gel-like product with 10 thousand BMMNCs in each ml of 1% hyaluronan (HA) solution RV-P1501-5: Gel-like product with 100 thousand BMMNCs in each ml of 1% hyaluronan (HA) solution RV-P1501-6: Gel-like product with 1 million BMMNCs in each ml of 1% hyaluronan (HA) solution

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

RV-P1501-4

Arm Type

Experimental

Arm Description

Gel-like product with 10 thousand BMMNCs in each ml of 1% hyaluronan (HA) solution

Arm Title

RV-P1501-5

Arm Type

Experimental

Arm Description

Gel-like product with 100 thousand BMMNCs in each ml of 1% hyaluronan (HA) solution

Arm Title

RV-P1501-6

Arm Type

Experimental

Arm Description

Gel-like product with 1 million BMMNCs in each ml of 1% hyaluronan (HA) solution

Intervention Type

Biological

Intervention Name(s)

RV-P1501

Intervention Description

Gel-like product with BMMNCs in each ml of hyaluronan (HA) solution

Primary Outcome Measure Information:

Title

Ankle Brachial Index (ABI)

Description

The percentage change of ABI from 3 follow-ups with the baseline.

Time Frame

Day 0, Week 4, Week 12, Week 24

Secondary Outcome Measure Information:

Title

Clinical status (Rutherford category)

Description

Improvement in Rutherford scale was recorded at baseline and each follow-up.

Time Frame

Day 0, Week 1, Week 2, Week 4, Week 12, Week 24

Title

Level of pain at rest

Description

Rest pain was measured using Wong-Baker FACES pain rating scale at baseline and each follow-up visit.

Time Frame

Day 0, Week 1, Week 2, Week 4, Week 12, Week 24

Title

Ulcer size in cm2

Description

Ulcer size was assessed and measured at each follow-up interval and compared to baseline.

Time Frame

Day 0, Week 1, Week 2, Week 4, Week 12, Week 24

Title

Ulcer category

Description

Ulcer status was assessed at each follow-up interval and compared to baseline.

Time Frame

Day 0, Week 1, Week 2, Week 4, Week 12, Week 24

Title

PWT/PFWT in seconds

Description

Peak walking time and pain-free walking time was measured at baseline and compared to W4, W12 and W24 by treadmill walking tests.

Time Frame

Day 0, Week 4, Week 12, Week 24

Title

Amputation free

Description

Time to below the knee amputation of the ipsilateral leg after the treatment.

Time Frame

Week 1, Week 2, Week 4, Week 12, Week 24

Title

Ejection fraction

Description

Ejection fraction was measured by echocardiogram to record the cardiac function at W12 and W24.

Time Frame

Week 12, Week 24

Title

CT angiography

Description

CT angiography was performed to record the morphology of blood vessel, location, and the vessel cross section percentage.

Time Frame

Week 12, Week 24

Title

Biochemistry

Description

Biochemistry tests were performed to interpret the health assessment at W12 and W24.

Time Frame

Week 12, Week 24

Title

Hematology

Description

Hematology tests were performed to interpret the health assessment at W12 and W24.

Time Frame

Week 12, Week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patient age ≥ 20 Patients with severe PAOD and diagnosed with Rutherford category 3, 4, or 5 Contraindication to angioplasty or bypass surgery, or post-angioplasty or bypass surgery for once but with limited or no effect. Patient without hypertension or hypertensive patient with adequate-controlled blood pressure. With signed informed consent Exclusion Criteria: Patient undergone any organ transplantation Inability to undergo bone marrow aspiration Pregnant woman Life expectancy < 1 year Cognitive impairment Active malignancy in 5 years prior to treatment Bleeding diathesis or pulmonary embolism Patient with active major cardiovascular diseases such as unstable angina, arrhythmia, heart failure, impaired cardiac function (ejection fraction < 45%), or stroke Estimated Glomerular Filtration Rate (eGFR) < 30 Glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) values higher than 80 U/L Patient with severe diabetes mellitus (HbA1C > 8%) Patient with alcohol addiction Patient with drug abuse Patient with infections or skin disease on the ischemic leg. Allergic to HA Patient whose blockage region only occurred in the femoral artery or at foot.

Facility Information:

Facility Name

National Cheng Kung University Hospital

City

Tainan

ZIP/Postal Code

704

Country

Taiwan

Facility Name

National Taiwan University Hospital

City

Taipei

ZIP/Postal Code

100

Country

Taiwan

12. IPD Sharing Statement

Plan to Share IPD

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Autologous BMMNC Combined With HA Therapy for PAOD

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