The Efficacy and Safety of REX-001 to Treat Ischemic Ulcers in Subjects With CLI Rutherford Category 5 and DM

NCT03174522 | Terminated Phase 3 DMC

• 1 other identifier: REX-001-005
• Study Type: interventional
• Target: 49
• Locations: 6 countries
• Sites: 15

Brief Summary

This trial is a pivotal, placebo-controlled, double-blind, parallel-group, adaptive trial conducted in subjects with DM and CLI Rutherford Category 5. 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Complete healing of all ischemic ulcers on the index leg.

  Change in Rutherford classification from CLI Category 5 to Category 4 or lower 12 months. after administration of REX-001 or placebo.

  The primary endpoint for this trial will be assessed at 12 months.

Study Arms (2)

REX-001

EXPERIMENTAL

REX-001 is a cell suspension of autologous bone marrow mononuclear cells (BM-MNCs) composed of several mature cell types.

Drug: REX-001

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

REX-001 DRUG

REX-001 is administered through an intra-arterial catheter.

REX-001

Placebo DRUG

Placebo is administered through an intra-arterial catheter.

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 5. For these patients, one of the following must be confirmed and documented at screening:
• Ankle systolic pressure \< 70 mmHg, or
• Toe systolic pressure \< 50 mmHg, or
• TcpO2 \< 30 mmHg (lying down). Subjects with non-compressible or calcified vessels must qualify on toe pressure or tcpO2.
• Poor or no revascularization option means that, in the opinion of the Investigator, revascularization using surgical or endovascular methods are not feasible due to for example the anatomy of existing vessels and/or existing comorbidity and/or previously failed surgical or endovascular revascularization.
• 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 must have a negative pregnancy test at screening. A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. 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. Effective contraceptive methods are e.g.:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal),
• Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable),
• Intrauterine device (IUD),
• Intrauterine hormone-releasing system (IUS),
• Bilateral tubal occlusion,

You may not qualify if:

• Subjects meeting any of the following criteria must not be enrolled in the trial:
• 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 4.
• 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. (34)
• A platelet count \< 50,000/μL.
• International normalized 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.

Sponsors & Collaborators

• Ixaka Ltd: lead
• Andalusian Network for Design and Translation of Advanced Therapies: collaborator

Study Sites (15)

Fakultní nemocnice Ostrava

Ostrava, Czechia

Location

Pécsi Tudományegyetem, PTE-KK I. sz Belgyógyászati Klinika

Pécs, Hungary

Location

Leids Universitair Medisch Centrum

Leiden, Netherlands

Location

Maastricht Universitair Medisch Centrum

Maastricht, Netherlands

Location

Hospital Garcia de Orta, EPE

Almada, Portugal

Location

Centro Hospitalar Lisboa Norte, EPE

Lisbon, Portugal

Location

Centro Hospitalar de São João

Porto, Portugal

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

Location

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Hospital Universitario Puerta del Mar

Cadiz, Spain

Location

First site: Hospital Universitario Reina Sofía

Córdoba, Spain

Location

Hospital Regional Universitario

Málaga, Spain

Location

Hospital General Universitario Morales Meseguer

Murcia, Spain

Location

University Hospital of Wales

Cardiff, United Kingdom

Location

MeSH Terms

Conditions

Peripheral Arterial Disease; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Chronic Limb-Threatening Ischemia

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Peripheral Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia

Study Officials

• Gilbert Wagener, MD

  Ixaka Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2017
• First Posted: June 2, 2017
• Study Start: April 25, 2017
• Primary Completion: February 13, 2023
• Study Completion: February 13, 2023
• Last Updated: March 16, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

PT (3); NL (2); GB (1); CZ (1); ES (7); HU (1)