Rexmyelocel-T (REX-001) has been administered to over 100 patients in three clinical trials: a phase I/II study in patients with critical limb ischemia (CLI and diabetes and two phase II studies, one in patients with CLI and diabetes patients and another in patients with CLI without diabetes. Two of these studies have been completed with the remaining study expected to complete during 2016. Rexgenero is also optimising the manufacturing process and plans to commence two confirmatory phase III studies in late 2016/early 2017. These studies are confirmatory Phase III clinical trials and the designs have been endorsed by CHMP of EMA including the two primary endpoints as well as the possibility to increase sample size at the interim analysis (adaptive design). CHMP/EMA have also confirmed that these two confirmatory studies would be sufficient for marketing authorisation. Both studies are double blind placebo-controlled trials; the first in patients with Rutherford category 4 CLI and diabetes and a second in patients with Rutherford category 5 CLI with diabetes. Both studies are expected to complete in late 2018.
Results from the first two clinical trials with diabetic patients have been highly encouraging. At the beginning of these studies patients were classified according to the severity of their disease according to the Rutherford scale. Patients were either Rutherford category 4 (rest pain without ulceration), category 5 (ulcers) or category 6 (severe ulcers/gangrene). Following treatment with Rexmyelocel-T, the majority of patients experienced a significant improvement in their clinical condition (as assessed by change in Rutherford category) with partial or complete ulcer healing and alleviation of rest pain.
Angiographic imaging was used to assess revascularisation following treatment. In the majority of treated patients there was a major improvement in blood vessels in the limb, which is likely to be responsible for the corresponding improvement in patient’s clinical condition.
> Angiograms showing blood vessels prior to treatment (left) and after 6 months
following treatment with REX-001 (Rexmyelocel-T) (right)
Patients with CLI often experience painful ischemic ulcers which may partially resolve with intensive wound management, but are rarely completely healed. Following treatment with REX-001 Rexmyelocel-T), the majority of patients with ulcers experienced complete or partial healing.
> Diabetic ulcer at baseline (left) and after 6 months following treatment with REX-001 (Rexmyelocel-T) (right)
Phase III diabetes study (NCT03174522/NCT03111238)
Two pivotal placebo-controlled double-blind parallel-group adaptive design Phase III clinical trial
– Efficacy and safety of Rexmyelocel-T to Treat Ischemic Rest Pain in Subjects With CLI Rutherford Category 4 and DM (NCT03111238/EudraCT2016-000240-34)
– Efficacy and safety of Rexmyelocel-T to Treat Ischemic Ulcers in Subjects With CLI Rutherford Category 5 and DM (EudraCT2016-003980-21)
Patient number: 138
Phase II diabetes study (NCT00987363)
Multi-centre phase II, randomized open-label clinical trial on the therapeutic use of intra-arterial infusion of autologous bone marrow mononuclear cells in diabetic patients with critical chronic ischemia of lower limbs
Patient number: 60
Phase II non-diabetes study (NCT01408381)
Multi-centre phase II, randomized open-label clinical trial on the therapeutic use of intra-arterial infusion of autologous bone marrow mononuclear cells in non-diabetic patients with critical chronic ischemia of lower limbs
Patient number: 33
Phase I/II diabetes study (NCT00872326)
Phase II clinical trial – Autologous Bone Marrow Derived Mononuclear Cells in Treating Diabetic Patients With Critical Limb Ischemia
Patient number: 20
Phase II diabetes study
Use of stem cell tissue mesenchymal adipose cell regeneration therapy in chronic lower limb critical limb ischemia in non-revascularizable diabetic patients
Patient number: 38
Completion: Q4 2016
Phase II non-diabetes study
Multi-centre, open label, randomized phase I/II clinical of the use of mesenchymal stem cells from adipose tissue as cellular regeneration therapy in chronic critical limb ischemia non-diabetes patients
Patient number: 30
Completion: Q1 2017
Phase II diabetes study
Multi-centre, open-label, randomized and controlled phase I/II clinical trial of stem cells as therapy for critical ischemia in lower limbs in insulinized type 2 diabetic patients
Patient number: 48