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

Sponsor

Ixaka Ltd (Industry)

Overall Status

Terminated

CT.gov ID

NCT03111238

Collaborator

Andalusian Network for Design and Translation of Advanced Therapies (Other)

Enrollment

Locations

Arms

47.8

Actual Duration (Months)

0.2

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Peripheral Arterial Disease (PAD) Diabetes Mellitus (DM) Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Cardiovascular Disease Critical Limb Ischemia (CLI)	Drug: REX-001 Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

3 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 5, 2017

Actual Primary Completion Date :

Mar 31, 2021

Actual Study Completion Date :

Mar 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: REX-001 REX-001 is a cell suspension of autologous BM-MNCs composed of several mature cell types.	Drug: REX-001 REX-001 is administered through an intra-arterial catheter.
Placebo Comparator: Placebo The final formulation of the placebo will be a diluted suspension of red blood cells.	Drug: Placebo Placebo is administered through an intra-arterial catheter.

Arm

Intervention/Treatment

Experimental: REX-001

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

Drug: REX-001

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

Placebo Comparator: Placebo

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

Drug: Placebo

Placebo is administered through an intra-arterial catheter.

Outcome Measures

Primary Outcome Measures

Complete relief of ischemic rest pain without developing ischemic lesions on the index leg. [The primary endpoint for this trial will be assessed at 12 months.]
Change in Rutherford classification from CLI Category 4 to Category 3 or lower 12 months after administration of REX-001 or placebo.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country
1	Fakultní nemocnice Ostrava	Ostrava		Czechia
2	Vitkovicka nemocnice a. s. Vaskularni centrum	Ostrava		Czechia
3	Klinikum der Goethe-Universität Frankfurt	Frankfurt		Germany
4	Pécsi Tudományegyetem, PTE-KK I. sz Belgyógyászati Klinika	Pécs		Hungary
5	Instytut Hematologii i Transfuzjologii	Warsaw		Poland
6	Centro Hospitalar de São João	Porto		Portugal
7	Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona	Spain
8	Hospital Universitari de Bellvitge	L'Hospitalet De Llobregat	Barcelona	Spain
9	Hospital Universitari Vall d'Hebron	Barcelona		Spain
10	Hospital Universitario Puerta del Mar	Cadiz		Spain
11	First site: Hospital Universitario Reina Sofía	Córdoba		Spain
12	Complejo Hospitalario Universitario de Granada, Hospital del Campus de la Salud	Granada		Spain
13	Hospital Universitario de la Princesa	Madrid		Spain
14	Hospital General Universitario Morales Meseguer	Murcia		Spain
15	Hospital Universitario Virgen de Valme	Sevilla		Spain