REX-001 to treat ischaemic ulcers in diabetic adults (Category 5)
Research type
Research Study
Full title
The Efficacy and Safety of Intra-Arterial Administration of REX-001 to treat ischaemic ulcers in subjects with critical limb ischaemia Rutherford Category 5 and diabetes mellitus: a pivotal, placebo-controlled, double-blind, parallel group, adaptive trial.
IRAS ID
219960
Contact name
Edwin Wagena
Contact email
Sponsor organisation
Rexgenero Limited
Eudract number
2016-003980-21
ISRCTN Number
ISRCTN00000000
Duration of Study in the UK
2 years, 9 months, 1 days
Research summary
This is a research study in patients with diabetes mellitus aged between 18 years and 85 years who have critical limb ischaemia (CLI) Rutherford Category 5, a condition which reduces blood flow to the lower limbs and feet. Pain can occur while at rest and which most often occurs at night, but in severe cases can be continuous and/or when walking. Leg ulcers or gangrene may also be present. The study involves an experimental product called Rexmyelocel-T (a cell therapy produced from autologous bone marrow). All participants will have a bone marrow sample taken and this will be processed in a laboratory. Participants will receive either Rexmyelocel-T or placebo, a look-alike treatment that has no active compound infused into their diseased arteries. The study will last 24 months; after the 12-month follow up visit has been completed for all participants those on placebo will be given the option to receive Rexmyelocel-T. It is hoped Rexmyelocel-T may improve wound healing on the leg, support existing arteries and stimulate the formation of new blood vessels to help improve circulation of blood to the leg, reduce pain and make walking easier. Rexmyelocel-T may help avoid disease progression to extended gangrene or amputation.
The information provided is an abbreviated report from a clinical study called "The Efficacy and Safety of Intra-Arterial Administration of REX-001 to Treat Ischaemic Ulcers in Subjects with Critical Limb Ischaemia Rutherford Category 5 and Diabetes Mellitus: A Pivotal, Placebo-Controlled, Double-Blind, Parallel-Group, Adaptive Trial." The study was conducted in accordance with Good Clinical Practice regulations and was a Phase 3 randomized, double-blind, placebo-controlled clinical trial that included patients with chronic limb threatening ischemia (CLTI) and diabetes.
The sample size was calculated based on the efficacy results from a Phase II trial conducted with REX-001 in 60 subjects with CLTI and diabetes. The study had two interim analyses, at 30% and 50%, and the primary endpoint was measured at month 12. The endpoints included the change in Rutherford classification from CLI Category 5 to Category 4 or lower 12 months after administration of REX-001 or placebo, change in Rutherford classification from CLI Category 5 to Category 3 or lower, change from baseline to visit 9 in
TcpO2 (transcutaneous oxygen pressure), partial healing of ischemic ulcers (≥ 50% reduction in size as compared to ulcer size at baseline), and amputation-free survival. Patients were administered with the investigational product or placebo one time at baseline, and then followed for 1-year with periodic visits every ~3 months for safety and efficacy assessment. Additionally, patients were monitored for an additional
12 months for safety assessment. Autologous bone marrow-derived white blood cells (BM-WBCs) isolated from the bone marrow, or placebo, in a 2:1 ratio, were administered to consenting subject one time at baseline. As the product was a biological product with minimal manipulation and autologous, there were no treatment-associated adverse events of any kind during the entire duration of the study.
The study was conducted with informed consent from all subjects before any trial procedure was conducted, and patients could have withdrawn from the study at any time without providing any justification. The primary objective of the study was to confirm the efficacy and safety of a single intra-arterial administration of REX-001 to treat ischemic ulcers in subjects with CLTI Rutherford Category 5 and diabetes.
The study was stopped prematurely by the independent data safety monitoring committee (DSMB) at its predetermined interim analysis at 50% of information due to futility in September of 2022.REC name
East of England - Cambridge Central Research Ethics Committee
REC reference
17/EE/0067
Date of REC Opinion
28 Jun 2017
REC opinion
Further Information Favourable Opinion