Clinical Trials
Critical Limb Ischemia (CLI)
PI - Prof. Timothy O' Brien
This trial was a Phase 1b, open label, uncontrolled and non-randomised dose-escalation stem cell clinical trial to treat Critical Limb Ischemia (CLI). The trial funded by the research partnership SFI-HRB and was approved by the HPRA (Health Products Regulatory Authority) in 2014.
Critical limb ischemia (CLI) is a severe blockage in the arteries of the lower extremities, which markedly reduces blood-flow. It is a serious form of peripheral arterial disease, or PAD. It is caused by atherosclerosis, the hardening and narrowing of the arteries over time due to the build-up of fatty deposits called plaque. CLI is a chronic condition severe pain in the feet or toes, even while resting. Complications of poor circulation can include sores and wounds that will not heal in the legs and feet. If left untreated, the complications of CLI may result in amputation of the affected limb.
The study examined the safety of intramuscular autologous transplantation of escalating doses of mesenchymal stem cells to patients with no-option critical limb ischemia (CLI).
Patient enrolment has finished and CCMI manufactured all batches for this trial.
A scientific paper detailing the outcomes of the clinical trial was recently published in the Journal, Cytotherapy (February 2020).
Adipoa-2
PI - Prof. Frank Barry
ADIPOA-2 is a clinical trial to treat people with mild to moderate osteoarthritis of the knee using autologous adult adipose-derived stromal cells (ASCs). The project is funded by the European Union’s Horizon 2020 programme involving CCMI and other facilities throughout Europe.
Osteoarthritis (OA) is an incurable and debilitating disease particularly affecting the joints of hands, knees, hips, and spines. It occurs when the protective cartilage that cushions the ends of bones wears down over time. It has been identified as the world’s eleventh highest contributor to disability and affects over 70 million Europeans. There is currently no treatment to prevent the progression of the disease.
ADIPOA-2 is a multi-centre, randomized clinical trial comparing the use of culture-expanded, autologous adult adipose-derived stromal cells (ASCs) in subjects with knee OA with injected Hyaluronan (another widely used therapeutic approach for knee degeneration). This study will involve two major elements: the production of consistent batches of high-quality autologous ASCs under GMP-compliant conditions and the delivery of these cell doses to patients in the trial. These doses have to meet all national and European regulatory and ethical standards, which will provide a definitive demonstration of the safety and efficacy of ASCs as a therapy for osteoarthritis.
The objective of the clinical trial is to generate efficacy and tolerability profiles of single injections of 2 dosages of autologous ASCs versus standard of care (placebo) when administered locally into a knee joint affected by OA after in vitro cell expansion. The potential of ASC to lead to a disease-modifying therapeutic option for the treatment of this chronic and debilitating disease will be assessed by MRI after 1 and 2 years.
Nephstrom
PI's - Prof. Timothy O'Brien & Prof. Matthew Griffin
NEPHSTROM is a clinical trial which is exploring the use of stem cells to treat diabetic kidney disease (DKD). The project is funded by the European Union’s Horizon 2020 programme involving CCMI and 11 European partners from Ireland, the UK, Germany, Italy, Belgium, and the Netherlands. It builds on the EU-funded project REDDSTAR which used stromal cells to treat diabetes mellitus.
Diabetes affects more the 400 million globally and its frequency is rapidly increasing. Diabetic kidney disease (DKD) or diabetic nephropathy is a serious complication of diabetes that commonly results in kidney failure requiring dialysis or kidney transplantation and greatly increases the risk of premature death due to heart and vascular disease. Approximately 25-30% of people with diabetes eventually develop DKD and, in most of them, the condition worsens over time resulting in a progressive loss of kidney function. Although lifestyle changes and a number of drug treatments can slow the progression of DKD, there is no curative or universally effective therapy. As a result, DKD had become the commonest cause of kidney failure worldwide and is a major contributor to early death among people with diabetes.
The NEPHSTROM project is focussed on carrying out an early-stage (Phase 1b/2a) clinical trial in which patients with DKD that is progressing toward kidney failure receive a single dose of an intravenous stem cell product manufactured at CCMI and three other European GMP cell manufacturing facilities. The cell therapy for the NEPHSTROM trial is called ORBCEL-M. It is a mesenchymal stem cell (MSC) product developed by the Galway-based Cell Technology company Orbsen Therapeutics Ltd. The product is manufactured from a specific type of MSC that is purified from bone marrow of healthy human volunteers. After purification, the cells are cultured to numbers large enough to treat several trial patients using the Terumo BCT Quantum Bioreactor. After being harvested from the bioreactor, the cells are cryopreserved (frozen) in single dose infusion bags and stored in a freezer until needed.
The NEPHSTROM trial is placebo-controlled, randomised, and blinded – meaning that the outcomes for patients that have received ORBCEL-M therapy can be compared without bias to those of similar patients that have received an inactive placebo. It is being carried out simultaneously at academic hospitals in Galway, Bergamo, Italy and Birmingham, UK. In total, it will treat 32 patients with ORBCEL-M and 16 with placebo. The main aim of the trial is to demonstrate the safety and feasibility of three different doses of ORBCEL-M in adults with DKD. In addition, each patient enrolled in the trial will have a range of clinical and research tests carried out during the 18 month follow-up period in order to investigate for signals of a therapeutic effect of ORBCEL-M and for evidence of the mechanisms of such an effect in patients that received the cell therapy compared to those that received placebo. Administration of ORBCEL-M/placebo to first of three groups of 16 patients (low, medium, and high dose groups) was completed in 2019 and the safety data from this group was favourably reviewed by the trial’s Drug Safety Monitoring Board. Enrolment in the second group of 16 patients starts in 2020. If the outcomes of the trial are encouraging, a larger, Phase 2 trial will be designed to build further evidence for the benefits of this cell therapy in DKD.
Visicort
PI's - Prof. Matthew Griffin
VISICORT is an EU funded clinical trial that aims to improve the success of corneal transplantation by better understanding the immune system responses that cause corneal transplant failure and by testing whether these adverse immune responses can be modulated with a stem cell therapy. The project is coordinated at NUI Galway and includes 11 other research and innovation partners in Ireland, the UK, Germany, France, and Denmark.
Corneal disease is a leading cause of blindness worldwide and affects individuals of both genders and of all age groups. Diseases of the cornea (the clear part of the front of the eye that allows light through the pupil to the retina) are one of the most common causes of visual loss and blindness worldwide and, when severe, require a corneal transplant to restore sight. Although the healthy cornea is protected from damage by the immune system, corneal transplants may be damaged by immune-mediated rejection, which remains the leading cause of corneal transplant failure. This is a particularly challenging problem in high-risk corneal transplant recipients, such as those with previous transplant failures due to rejection or those with eye diseases that cause intense inflammation of the cornea and/or growth of blood vessels into the cornea.
The VISICORT project incorporates the performance of an early-stage (Phase 1b) clinical trial of a mesenchymal stem cell (MSC) therapeutic product manufactured at CCMI from the bone marrow of healthy adult volunteers and given intravenously to patients who are receiving a second or greater full-thickness corneal transplant for loss of vision due to failure of a previous transplant at the Charité University Hospital in Berlin, Germany. Once manufactured, the VISICORT cell product (allogeneic human bone marrow-derived MSC – allo-hBM-MSC) will be stored as frozen doses at CCMI then transported to Berlin to be thawed and administered to trial patients as intravenous infusions 7 days and 1 day before the corneal transplant procedure. The trial is an open-label trial in which two groups of 4 corneal re-transplant recipients each will receive intravenous infusions of allo-hBM-MSC. The first group will receive lower doses and the second group higher doses. Trial patients will be followed closely for 12 weeks after transplantation to determine the safety of the cell therapy. Continued clinical follow-up will be performed to learn the longer-term outcomes of the transplants.
The main aim of the VISICORT clinical trial project is to test the safety and feasibility of intravenous allo-hBM-MSC in patients receiving a full-thickness corneal transplant who are at high risk for rejection. Through extensive clinical examination and research tests of blood and other samples collected through the trial, it will also be possible to gather preliminary information about the potential benefits of the cell therapy on corneal transplant rejection risk and immune responses.
In 2019, CCMI received regulatory approval for the production of allo-hBM-MSC for the VISICORT using the Terumo BCT Quantum Bioreactor. Regulatory and ethical approval was also received in 2019 for initiation of the VISICORT clinical trial at Charité University Hospital and Charité Research Organisation. Cell manufacturing for the trial will begin in 2020.
