Autologous BMMNC Combined With HA Therapy for PAOD

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Peripheral Arterial Occlusive Disease; Critical Limb Ischemia
• Intervention / Treatment: Biological: RV-P1501

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.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RV-P1501-4; Gel-like product with 10 thousand BMMNCs in each ml of 1% hyaluronan (HA) solution	Biological: RV-P1501; Gel-like product with BMMNCs in each ml of hyaluronan (HA) solution
Experimental: RV-P1501-5; Gel-like product with 100 thousand BMMNCs in each ml of 1% hyaluronan (HA) solution	Biological: RV-P1501; Gel-like product with BMMNCs in each ml of hyaluronan (HA) solution
Experimental: RV-P1501-6; Gel-like product with 1 million BMMNCs in each ml of 1% hyaluronan (HA) solution	Biological: RV-P1501; Gel-like product with BMMNCs in each ml of hyaluronan (HA) solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ankle Brachial Index (ABI)	The percentage change of ABI from 3 follow-ups with the baseline.	Day 0, Week 4, Week 12, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical status (Rutherford category)	Improvement in Rutherford scale was recorded at baseline and each follow-up.	Day 0, Week 1, Week 2, Week 4, Week 12, Week 24
Level of pain at rest	Rest pain was measured using Wong-Baker FACES pain rating scale at baseline and each follow-up visit.	Day 0, Week 1, Week 2, Week 4, Week 12, Week 24
Ulcer size in cm2	Ulcer size was assessed and measured at each follow-up interval and compared to baseline.	Day 0, Week 1, Week 2, Week 4, Week 12, Week 24
Ulcer category	Ulcer status was assessed at each follow-up interval and compared to baseline.	Day 0, Week 1, Week 2, Week 4, Week 12, Week 24
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.	Day 0, Week 4, Week 12, Week 24
Amputation free	Time to below the knee amputation of the ipsilateral leg after the treatment.	Week 1, Week 2, Week 4, Week 12, Week 24
Ejection fraction	Ejection fraction was measured by echocardiogram to record the cardiac function at W12 and W24.	Week 12, Week 24
CT angiography	CT angiography was performed to record the morphology of blood vessel, location, and the vessel cross section percentage.	Week 12, Week 24
Biochemistry	Biochemistry tests were performed to interpret the health assessment at W12 and W24.	Week 12, Week 24
Hematology	Hematology tests were performed to interpret the health assessment at W12 and W24.	Week 12, Week 24

Collaborators and Investigators

• Sponsor: Academia Sinica, Taiwan
• Collaborators: National Taiwan University Hospital; National Cheng-Kung University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2017
• Primary Completion (Anticipated): June 30, 2018
• Study Completion (Actual): July 27, 2018

Study Registration Dates

• First Submitted: July 5, 2017
• First Submitted That Met QC Criteria: July 10, 2017
• First Posted (Actual): July 12, 2017

Study Record Updates

• Last Update Posted (Actual): March 15, 2022
• Last Update Submitted That Met QC Criteria: March 1, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Hyaluronan; Bone marrow mononuclear cells
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Ischemia; Arterial Occlusive Diseases
• Other Study ID Numbers: AS-IRB-BM-14056

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No