Industry Update: Clinical trials

Latest clinical trial developments compiled from January 1 — February 29 2016

Latest business developments in the field of stem cell research and
regenerative medicine compiled from publicly available information and
press releases from non-academic institutions from January 1 — February 29 2016, scheduled to be published in Volume 11 Issue 4 of Regenerative Medicine.

Athersys

Data presented by Athersys (CA, US; www.athersys.com) indicates that stroke patients treated by an adult stem cell therapy called MultiStem® did significantly better than others who received a placebo one year after treatment. The results are from a Phase 2 study involving clinical sites in the USA and the UK. The study examined the safety and effectiveness of the new therapy developed for the treatment of ischemic stroke. Of the 65 patients treated with MultiStem, 23.1% achieved a complete or near full recovery from their stroke after one year. Only 8.2% of the 61 placebo patients achieved that level of recovery. Patients who received the cell therapy within 36 hours after the onset of stroke did even better, with 29% of those 31 patients achieving an excellent outcome. Additional information about the clinical trial is available at http://clinicaltrials.gov (ID: NCT01436487).

Bone Therapeutics

Bone Therapeutics (Belgium; www.bonetherapeutics.com) initiated a Phase IIA study for the treatment of multiple delayed-union fractures with ALLOB®, its novel allogeneic bone cell therapy product. The new Phase IIA study aims to extend the ongoing trial from the treatment of single fractures to multiple fractures. The study will enroll 12 patients, diagnosed with multiple delayed-union fractures of long bones, across six sites in Belgium and four sites in Germany. Patients will receive two to four percutaneous injections of ALLOB at two, three or four fracture sites on the same or different long bones, while a single dose at one site is used in the initial delayed-union study. The study will thus allow the evaluation of the safety and efficacy of higher doses of ALLOB. Patients will be recruited in cohorts of four and initial safety data of each cohort will be analyzed by the Safety Monitoring Committee before recruitment of the next patients to ensure maximum patient safety. Fracture healing in the ALLOB-treated patients will be evaluated over a six-month period using clinical and radiological parameters.

Caladrius

Caladrius BioSciences (NY, US; www.caladrius.com) discontinued its Phase 3 clinical trial evaluating a novel cell therapy for patients with metastatic melanoma, a potentially lethal form of skin cancer. Caladrius indicated the project was terminated because outcomes for patients with the disease had improved so much since the product entered development that enrolling a sufficient number of patients in a timely manner to demonstrate a statistical benefit had become very difficult. The product has been in development since 1990. Additional information about the clinical trial is available at http://clinicaltrials.gov (ID: NCT01875653).

Capricor

Capricor Therapeutics (CA, US; www.capricor.com) announced continuing enrollment of and the treatment of the first patient with Duchenne Muscular Dystrophy (DMD)-related cardiomyopathy with CAP1002 in the HOPE-Duchenne Phase I/II clinical trial (Halt cardiomyOPathy progrEssion in Duchenne). CAP1002 is Capricor’s allogeneic, cardio-sphere-derived stem cell (CDC) therapy. The patient was treated at the Cincinnati Children’s Hospital Medical Center. Enrollment is now ongoing at Cincinnati Children’s Hospital Medical Center in Cincinnati, Ohio and at Cedars-Sinai Heart Institute in Los Angeles, California. The HOPE-Duchenne trial is designed to enroll 24 patients in a randomized, multicenter study evaluating the safety and efficacy of CAP1002. Patients randomized to receive the cells will receive CAP1002 in all three coronary arteries which will enable delivery extensively across the myocardium. Improvement in cardiac function was recently reported using this approach in Capricor’s DYNAMIC trial for adult patients with Class III Heart Failure. Cardiomyopathy is currently the leading cause of death in patients with DMD now that other treatments are available to mitigate other aspects of the disease process. Additional information about these clinical trials is available at http://clinicaltrials.gov (ID: NCT02485938 and NCT02293603).

Cellular Biomedicine Group

Cellular Biomedicine Group (CA, US; www.cellbiomedgroup.com) has launched a Phase I clinical trial of an off-the-shelf allogeneic adipose-derived mesenchymal progenitor cell AlloJoinTM therapy for Knee Osteoarthritis. Additional information about the clinical trial is available at http://clinicaltrials.gov (ID: NCT02641860).

Cytori

Cytori Therapeutics (CA, US; www.cytori.com) enrolled the first two patients in an investigator-initiated clinical trial of Cytori Cell Therapyâ„¢ for the treatment of the orphan indication, fistula-in-ano associated with Crohn’s Disease. This 10 patient open label trial is being performed at the Hôpital Nord, Marseille, France under the authority of the Agence Nationale de Sécurité du Médicament (ANSM; http://ansm.sante.fr/), the French equivalent of the US FDA. As with the SCLERADEC I trial of Cytori Cell Therapy performed by a different group in Marseille, this trial is being executed in an indication that has been recognized as orphan by both the European Medicines Agency and the US FDA. Fistula-in-ano is an abnormal tunnel linking the interior of the lower intestine to the skin adjacent to the anus such that the contents of the intestines can leak through bypassing the anal sphincter. They are associated with substantial pain, risk of infection, and reduced quality of life. Fistulas occur in 20-40% of patients with Crohn’s Disease with approximately 90% of these requiring surgical intervention. More than 20% of patients do not achieve complete healing and recurrence is common, occurring in 20-35% of cases.

Stemedica Cell Technologies

Stemedica Cell Technologies (CA, US; www.stemedica.com) has completed enrollment into “A Phase I/IIa, Multi-Center, Open-Label Study to Assess the Safety, Tolerability, and Preliminary Efficacy of a Single Intravenous Dose of Allogeneic Mesenchymal Bone Marrow Cells to Subjects with Ischemic Stroke.” This study focused on patients who were at least six months post-stroke with significant functional or neurologic impairment. Inclusion criteria specified that patients have no substantial improvement in neurologic or functional deficits for the two months prior to enrollment in the study. The primary goal of this study is to evaluate the safety and tolerability of Stemedica’s ischemia-tolerant allogeneic mesenchymal bone marrow cells (itMBMC) administered intravenously. Patient status is assessed at specified time points over a period of 12 months using the following assessment scales: National Institutes of Health Stroke Scale (NIHSS), Mini Mental Status Exam (MMSE), Barthel Index (BI) and The Geriatric Depression Scale (GDS). Phase I of this trial was a dose-escalation study evaluating three doses of stem cells, with five subjects per dose receiving itMBMC based on weight: 0.5, 1.0 and 1.5 million cells/kg per of body weight. At the completion of the treatment of each dose cohort, a safety review was conducted by a Data Safety Monitoring Board (DSMB) prior to treatment at the next dose level. Fifteen patients were treated in Phase I of this study and the DSMB unanimously recommended continuing the study into Phase IIa. An additional 21 patients were treated at a dose of 1.5 million cells/kg body weight. Of the 36 patients treated in this study, 14 patients have already completed a 12-month follow-up. Only one mild adverse event was attributed to the investigational product. No clinically-significant changes in laboratory or imaging results were reported. Although the cells are allogeneic, the laboratory findings did not indicate an immune response and no immunosuppressive drugs were used in the clinical study. The majority of patients experienced improvement of their conditions in comparison to the baselines as assessed by the NIHSS, MSE, BI and GDS scales. Additional information about the clinical trial is available at http://clinicaltrials.gov (ID: NCT01297413).