Industry Update: Clinical trials

Latest clinical trial developments compiled from October 01 — November 30 2016

Latest clinical trial developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from non-academic institutions from October 01 — November 30 2016, scheduled to be published in Volume 12 Issue 2 of Regenerative Medicine.

Clinical trials

Asterias

Asterias Biotherapeutics (CA, USA; www.asteriasbiotherapeutics.com) announced that the first patient with the American Spinal Injury Association Impairment Scale (AIS)-A complete cervical spinal cord injury was successfully administered the highest dose of 20 million cells of AST-OPC1 (oligodendrocyte progenitor cells) in the SCiStar clinical trial (https://clinicaltrials.gov; ID: NCT02302157) at Santa Clara Valley Medical Center (CA, USA; www.scvmc.org). The SCiStar trial is an open-label, single-arm trial testing three sequential escalating doses of AST-OPC1 administered at up to 20 million in 35 patients with sub-acute, C-5 to C-7, motor complete (AIS-A patients, who have lost all motor and sensory function below their injury site, or AIS-B patients, who lost all motor functions but retain some sensory function) cervical SCI at day 14 to day 30 post-injury. Asterias is continuing enrollment in the AIS-B 10 million cells cohort with a second patient now dosed. No serious or unexpected adverse events related to AST-OPC1 have been reported so far.

BioTime

BioTime (CA, USA; www.biotimeinc.com) announced data from its Renevia® pivotal trial. Developed as an alternative for whole adipose tissue fat transfer procedures for facial HIV-lipoatrophy patients, Renevia is designed to mimic the naturally-occuring extracellular matrix and provide a 3-D scaffold that enables effective cell transplant and engraftment. In the run-in portion of this trial, the Renevia administration procedure was found to be reproducible, and the pivotal trial is now into its controlled phase. Encouraging signs of Renevia being able to promote new tissue generation were seen with the run-in practice patients

Capricor

Capricor Therapeutics (CA, USA; http://capricor.com) announced that its Phase II ALLogeneic Heart STem Cells to Achieve Myocardial Regeneration, ALLSTAR, clinical trial has completed patient enrollment (www.clinicaltrials.gov, ID: NCT01458405). ALLSTAR is a randomized, double-blind, placebo-controlled Phase II trial testing allogeneic cardiosphere-derived cells (CDCs — called CAP-1002) in adults with cardiac dysfunction following a myocardial infarction. At 30 centers in the U.S. and Canada, 142 subjects were randomized to the active or control treatment groups in a 2:1 ratio, respectively, of whom 134 received a single infusion of either CAP-1002 or placebo into the infarct-associated coronary artery. Patients were stratified according to time between infarct event and study medication infusion (Recent MI = 30 — 90 days; Chronic MI = 91 — 365 days). Following infusion, patients will be followed for periodic evaluations over the course of one year. At 12-month post-infusion, infarct size will be assessed by magnetic resonance imaging. As well as evaluate the safety and tolerability of CAP-1002, ALLSTAR will also explore additional efficacy parameters, such as ejection fraction and cardiac volumes.

In unrelated press release, Capricor announced that it intends to expand its CAP-1002 clinical development program in Duchenne muscular dystrophy (DMD) to encompass the skeletal muscle aspects of the disease, in addition to the cardiac complications. In the planned study, the medication will be given by systemic intra-vascular administration. This trial is expected to begin in 2017 subject to regulatory approval, and is intended to enroll people with DMD irrespective of their mutation or ambulatory status. Capricor is currently conducting the randomized, controlled Phase I/II HOPE clinical trial (www.clinicaltrials.gov, ID: NCT02485938) of CAP-1002 in DMD-associated cardiomyopathy. In HOPE, 13 patients received a single dose of CAP-1002 via intra-coronary triple-vessel infusion and 12 patients are receiving usual care, with those randomized to the control arm to be eligible to receive CAP-1002 following the completion of their 12-month follow-up. Subject to regulatory review, Capricor is exploring the possibility of re-dosing patients in the active arm who complete the 12-month trial period. It is hoped that patients who initially respond to CAP-1002 will become eligible for repeat dosing.

InGeneron

InGeneron (TX, USA; www.ingeneron.com) presented initial data from an investigator initiated case series using its proprietary adipose-derived regenerative cell (ADRC) technology for the treatment of facet joint syndrome, one of the major causes of chronic back pain. The case series comprised 19 male patients ranging in age from 31 to 71 years presenting with facet joint syndrome and treated with autologous ADRCs prepared at point of care through InGeneron’s proprietary technology. Patients reported a significant average pain decrease from 7.2 to 1.8 on a Visual Analogue Scale (VAS) and an Oswestry Disability Index (ODI) reduction from 74.3% to 19.1%. Over the average follow-up period of 13.2-months post treatment, patients reported continued pain reduction and no adverse events, demonstrating good overall safety and tolerability.

jCyte

jCyte (CA, USA; www.jcyte.com) has completed enrollment in a phase I/IIa trial to study the safety of its stem cell therapy candidate for retinitis pigmentosa (https://clinicaltrials.gov; ID: NCT02320812). The company’s investigational therapy, called jCell, uses injected retinal progenitor cells, which are intended to rescue dying retinal cells (rods and cones) and possibly regenerate new ones. The non-surgical treatment requires a single intravitreal injection, which can be performed in an ophthalmologist’s office under local anesthesia. The trial included 28 patients with advanced retinitis pigmentosa, eight of whom have completed the one-year study. Early safety results have been promising.

Stemedica

Stemedica International, a subsidiary of Stemedica Cell Technologies (CA, USA, www.stemedica.com), that uses its proprietary allogeneic stem-cell therapies for Alzheimer’s disease, enrolled its first patient at the University of California, Irvine (UCI; CA, USA; www.uci.edu). The study is a Phase IIa Multicenter, Randomized, Single-blind, Placebo-controlled, crossover study to assess the safety, tolerability, and preliminary efficacy of a single intravenous dose of allogeneic human Mesenchymal Stem Cells (MSC) in subjects with mild to moderate dementia due to Alzheimer’s disease (STEM4ADTMâ„¢; https://clinicaltrials.gov; ID: NCT02833792). The study will enroll approximately 40 subjects diagnosed at least 3 months prior to enrollment, based on the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s disease and Related Disorders Association (NINCDS-ADRDA) Alzheimer’s criteria. Stemedica’s bone marrow-derived, allogeneic ischemic-tolerant MSC (itMSCs) are grown under hypoxic conditions, and, compared to other MSCs, they secrete higher levels of growth factors associated with angiogenesis and healing.

Zimmer Biomet

Zimmer Biomet (IN, USA, www.zimmerbiomet.com) has updated its Investigational Device Exemption (IDE) clinical trial evaluating the use of autologous concentrated bone marrow aspirate (cBMA), prepared utilizing the MarrowStim^TM PAD Kit device, for the treatment of critical limb ischemia (CLI). The trial (https://clinicaltrials.gov; ID: NCT01049919), known as MOBILE (MarrOwStimTM PAD Kit for the Treatment of Critical LimB IschemIa in Subjects with Severe Peripheral ArteriaL DiseasE; www.padstudy.org/trials), is a prospective, randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of cBMA, injected intramuscularly into the affected limb, in preventing or delaying major amputation and/or death in patients with CLI who are unsuitable for revascularization. The primary efficacy endpoint of the study is amputation free survival, time to major amputation and/or all cause mortality, at 1 year. A preliminary analysis of a partial data set found that treatment with cBMA improved amputation-free survival compared to placebo, while maintaining a safety profile comparable to placebo.