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The Efficacy and Safety of REX-001 to Treat Ischemic Rest Pain in Subjects With CLI Rutherford Category 4 and DM

Primary Purpose

Peripheral Arterial Disease (PAD), Diabetes Mellitus (DM), Diabetes Mellitus, Type 1

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
REX-001
Placebo
Sponsored by
Ixaka Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peripheral Arterial Disease (PAD) focused on measuring Autologous, Bone Marrow-derived Mononuclear Cells (BM-MNCs), Advanced Therapy Medicinal Product (ATMP), Tissue-engineered Medicinal Product, Revascularization, Angiogenesis, Vasculogenesis, Arteriogenesis

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Aged ≥ 18 to ≤ 85 years.
  2. Diagnosis of Type I or II DM, established more than one year ago.
  3. Glycosylated hemoglobin (HbA1c) < 9%.
  4. Subjects with poor or no (surgical or endovascular) revascularization option classified as CLI Rutherford Category 4. The blood circulation in these subjects must be compromised at screening, defined as:

    • Ankle systolic pressure < 50 mm Hg, or
    • Toe systolic pressure < 30 mm Hg, or
    • TcpO2 < 30 mm Hg, and
    • Flat or barely pulsatile ankle or metatarsal PVR
  5. In the opinion of the Investigator, the subject is controlled on medical therapy indicated for CLI (unless there is a documented contraindication or intolerance) and pain management is optimized.
  6. Women of childbearing potential (i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile) must have a negative pregnancy test at screening. Men and women who are sexually active shall use effective contraceptive methods for the duration of their participation in this study if the partner of the male participant, or if the female participant is of childbearing potential.

Exclusion Criteria:

  1. Advanced CLI defined as presence of major tissue loss as significant ulceration/gangrene proximal to the metatarsal heads (CLI Rutherford Category 6). Significant ulceration/gangrene means any ulceration that extends beyond the subcutaneous tissue layer, or any gangrene or tissue necrosis proximal to the metatarsal heads.
  2. CLI Rutherford Category 5.
  3. Uncontrolled or untreated proliferative retinopathy.
  4. Failed surgical or endovascular revascularization on the index leg within 10 days after the procedure.
  5. Subjects in whom arterial insufficiency in the lower extremity is the result of acute limb ischemia or an immunological or inflammatory or non-atherosclerotic disorder (e.g., thromboangiitis obliterans (Buerger's Disease), systemic sclerosis (both limited and diffuse forms).
  6. Clinical evidence of invasive infection on index leg defined as major tissue loss at the mid-foot or heel involving tendon and/or bone, and/or when intravenous antibiotics are required to treat the infection according to the Investigator.
  7. At screening, the presence of only neuropathic ulcers on the index leg.
  8. Amputation at or above the talus on the index leg.
  9. Planned major amputation within the first month after randomization.
  10. On the index leg, use of concomitant wound treatments not currently approved for ischemic wound-healing within 30 days prior to screening or plans to initiate new, nonstandard-of-care treatments to the index leg during the trial.
  11. Blood clotting disorder not caused by medication (e.g., thrombophilia).
  12. Severe hypertension according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.
  13. A platelet count < 50,000/ μL.
  14. International normalised ratio (INR) > 1.5. For patients on anticoagulant medication an INR > 1.5 is allowed, provided that the Investigator and the haematologist consider the patient eligible to collect BM.
  15. Evidence of moderate to severe hepatocellular dysfunction according to the treating physician.
  16. Positive test for human immunodeficiency virus 1 (HIV 1), HIV 2, hepatitis B virus (HBV), hepatitis C virus (HCV) or Treponema pallidum.
  17. Subjects who may not be healthy enough to successfully complete all protocol requirements including BM collection, or who are not expected to survive more than 12 months, or in whom results may be particularly difficult to assess, as assessed by the Investigator.
  18. Subjects who participate in another clinical interventional trial.
  19. Subjects who have been treated with experimental medication within 30 days of screening.
  20. Subjects who were treated with other cell therapies for CLI within the last 12 months preceding the screening visit.

Sites / Locations

  • Fakultní nemocnice Ostrava
  • Vitkovicka nemocnice a. s. Vaskularni centrum
  • Klinikum der Goethe-Universität Frankfurt
  • Pécsi Tudományegyetem, PTE-KK I. sz Belgyógyászati Klinika
  • Instytut Hematologii i Transfuzjologii
  • Centro Hospitalar de São João
  • Hospital Universitari Germans Trias i Pujol
  • Hospital Universitari de Bellvitge
  • Hospital Universitari Vall d'Hebron
  • Hospital Universitario Puerta del Mar
  • First site: Hospital Universitario Reina Sofía
  • Complejo Hospitalario Universitario de Granada, Hospital del Campus de la Salud
  • Hospital Universitario de la Princesa
  • Hospital General Universitario Morales Meseguer
  • Hospital Universitario Virgen de Valme

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

REX-001

Placebo

Arm Description

REX-001 is a cell suspension of autologous BM-MNCs composed of several mature cell types.

The final formulation of the placebo will be a diluted suspension of red blood cells.

Outcomes

Primary Outcome Measures

Complete relief of ischemic rest pain without developing ischemic lesions on the index leg.
Change in Rutherford classification from CLI Category 4 to Category 3 or lower 12 months after administration of REX-001 or placebo.

Secondary Outcome Measures

Full Information

First Posted
April 7, 2017
Last Updated
May 5, 2021
Sponsor
Ixaka Ltd
Collaborators
Andalusian Network for Design and Translation of Advanced Therapies
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1. Study Identification

Unique Protocol Identification Number
NCT03111238
Brief Title
The Efficacy and Safety of REX-001 to Treat Ischemic Rest Pain in Subjects With CLI Rutherford Category 4 and DM
Official Title
The Efficacy and Safety of Intra-arterial Administration of REX-001 to Treat Ischemic Rest Pain in Subjects With Critical Limb Ischemia (CLI) Rutherford Category 4 and Diabetes Mellitus (DM): a Pivotal, Placebo-controlled, Double-blind, Parallel-group, Adaptive Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Terminated
Why Stopped
Stopped due to inactivity
Study Start Date
April 5, 2017 (Actual)
Primary Completion Date
March 31, 2021 (Actual)
Study Completion Date
March 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ixaka Ltd
Collaborators
Andalusian Network for Design and Translation of Advanced Therapies

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This trial is a pivotal, placebo-controlled, double-blind, parallel-group, adaptive trial conducted in subjects with DM and CLI Rutherford Category 4. Minimisation will be used to assign eligible subjects in a 2:1 ratio to receive a single intra-arterial administration of REX-001 or matching placebo into the index limb.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral Arterial Disease (PAD), Diabetes Mellitus (DM), Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Cardiovascular Disease, Critical Limb Ischemia (CLI)
Keywords
Autologous, Bone Marrow-derived Mononuclear Cells (BM-MNCs), Advanced Therapy Medicinal Product (ATMP), Tissue-engineered Medicinal Product, Revascularization, Angiogenesis, Vasculogenesis, Arteriogenesis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
REX-001
Arm Type
Experimental
Arm Description
REX-001 is a cell suspension of autologous BM-MNCs composed of several mature cell types.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
The final formulation of the placebo will be a diluted suspension of red blood cells.
Intervention Type
Drug
Intervention Name(s)
REX-001
Intervention Description
REX-001 is administered through an intra-arterial catheter.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo is administered through an intra-arterial catheter.
Primary Outcome Measure Information:
Title
Complete relief of ischemic rest pain without developing ischemic lesions on the index leg.
Description
Change in Rutherford classification from CLI Category 4 to Category 3 or lower 12 months after administration of REX-001 or placebo.
Time Frame
The primary endpoint for this trial will be assessed at 12 months.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Aged ≥ 18 to ≤ 85 years. Diagnosis of Type I or II DM, established more than one year ago. Glycosylated hemoglobin (HbA1c) < 9%. Subjects with poor or no (surgical or endovascular) revascularization option classified as CLI Rutherford Category 4. The blood circulation in these subjects must be compromised at screening, defined as: Ankle systolic pressure < 50 mm Hg, or Toe systolic pressure < 30 mm Hg, or TcpO2 < 30 mm Hg, and Flat or barely pulsatile ankle or metatarsal PVR In the opinion of the Investigator, the subject is controlled on medical therapy indicated for CLI (unless there is a documented contraindication or intolerance) and pain management is optimized. Women of childbearing potential (i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile) must have a negative pregnancy test at screening. Men and women who are sexually active shall use effective contraceptive methods for the duration of their participation in this study if the partner of the male participant, or if the female participant is of childbearing potential. Exclusion Criteria: Advanced CLI defined as presence of major tissue loss as significant ulceration/gangrene proximal to the metatarsal heads (CLI Rutherford Category 6). Significant ulceration/gangrene means any ulceration that extends beyond the subcutaneous tissue layer, or any gangrene or tissue necrosis proximal to the metatarsal heads. CLI Rutherford Category 5. Uncontrolled or untreated proliferative retinopathy. Failed surgical or endovascular revascularization on the index leg within 10 days after the procedure. Subjects in whom arterial insufficiency in the lower extremity is the result of acute limb ischemia or an immunological or inflammatory or non-atherosclerotic disorder (e.g., thromboangiitis obliterans (Buerger's Disease), systemic sclerosis (both limited and diffuse forms). Clinical evidence of invasive infection on index leg defined as major tissue loss at the mid-foot or heel involving tendon and/or bone, and/or when intravenous antibiotics are required to treat the infection according to the Investigator. At screening, the presence of only neuropathic ulcers on the index leg. Amputation at or above the talus on the index leg. Planned major amputation within the first month after randomization. On the index leg, use of concomitant wound treatments not currently approved for ischemic wound-healing within 30 days prior to screening or plans to initiate new, nonstandard-of-care treatments to the index leg during the trial. Blood clotting disorder not caused by medication (e.g., thrombophilia). Severe hypertension according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. A platelet count < 50,000/ μL. International normalised ratio (INR) > 1.5. For patients on anticoagulant medication an INR > 1.5 is allowed, provided that the Investigator and the haematologist consider the patient eligible to collect BM. Evidence of moderate to severe hepatocellular dysfunction according to the treating physician. Positive test for human immunodeficiency virus 1 (HIV 1), HIV 2, hepatitis B virus (HBV), hepatitis C virus (HCV) or Treponema pallidum. Subjects who may not be healthy enough to successfully complete all protocol requirements including BM collection, or who are not expected to survive more than 12 months, or in whom results may be particularly difficult to assess, as assessed by the Investigator. Subjects who participate in another clinical interventional trial. Subjects who have been treated with experimental medication within 30 days of screening. Subjects who were treated with other cell therapies for CLI within the last 12 months preceding the screening visit.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilbert Wagener, MD
Organizational Affiliation
Ixaka Limited
Official's Role
Study Director
Facility Information:
Facility Name
Fakultní nemocnice Ostrava
City
Ostrava
Country
Czechia
Facility Name
Vitkovicka nemocnice a. s. Vaskularni centrum
City
Ostrava
Country
Czechia
Facility Name
Klinikum der Goethe-Universität Frankfurt
City
Frankfurt
Country
Germany
Facility Name
Pécsi Tudományegyetem, PTE-KK I. sz Belgyógyászati Klinika
City
Pécs
Country
Hungary
Facility Name
Instytut Hematologii i Transfuzjologii
City
Warsaw
Country
Poland
Facility Name
Centro Hospitalar de São João
City
Porto
Country
Portugal
Facility Name
Hospital Universitari Germans Trias i Pujol
City
Badalona
State/Province
Barcelona
Country
Spain
Facility Name
Hospital Universitari de Bellvitge
City
L'Hospitalet De Llobregat
State/Province
Barcelona
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario Puerta del Mar
City
Cadiz
Country
Spain
Facility Name
First site: Hospital Universitario Reina Sofía
City
Córdoba
Country
Spain
Facility Name
Complejo Hospitalario Universitario de Granada, Hospital del Campus de la Salud
City
Granada
Country
Spain
Facility Name
Hospital Universitario de la Princesa
City
Madrid
Country
Spain
Facility Name
Hospital General Universitario Morales Meseguer
City
Murcia
Country
Spain
Facility Name
Hospital Universitario Virgen de Valme
City
Sevilla
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

The Efficacy and Safety of REX-001 to Treat Ischemic Rest Pain in Subjects With CLI Rutherford Category 4 and DM

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