Industry Update: Clinical trials

Latest clinical trial developments compiled from 1—31 July 2015

Latest developments in the field of stem cell research and regenerative
medicine compiled from publicly available information and press releases
from non-academic institutions 1—31 July 2015, scheduled to be
published in Volume 10 Issue 8 of Regenerative Medicine.

Bavarian Nordic

Bavarian Nordic (Denmark; www.bavarian-nordic.com) announced that the first patient has been enrolled in a new phase 2 clinical study of PROSTVAC, the Company’s active prostate cancer immunotherapy candidate. The study is designed as a randomized, double blind, placebo controlled study for men who have localized prostate cancer, and are undergoing active surveillance. These patients are not experiencing symptoms related to their cancer, and are not being treated with other therapies. The National Cancer Institute (NCI) sponsored the study as part of a Collaborative Research and Development Agreement (CRADA) and Clinical Supply Agreement between Bavarian Nordic and the NCI. The study will be conducted across 6 sites, and is designed to enroll 90 patients with the potential to expand up to 150 patients. The primary endpoint of the study is to determine how well PROSTVAC works in eliciting an immune response in patients with prostate cancer that is found only in the prostate and has not yet metastasized. Changes in CD8 and CD4 T cells in tissue adjacent to the tumor and within malignant portion of prostate biopsies will be measured, as will changes in prostate-specific antigen (PSA). Secondary endpoints include effects of PROSTVAC on changes in CD274 or programmed death-ligand 1 (PD-L1) expression, PSA doubling time, and change in tumor grade (Gleason score). Additional information on this study can be found at www.clinicaltrials.gov (ID: NCT02326805).

BioLinex and Bellerophon

BioLineRx (Israel; www.biolinerx.com) and its partner, Bellerophon (NJ, USA; www.bellerophon.com) reported top-line results from its PRESERVATION I clinical trial for bioabsorbable cardiac matrix, also known as IK-5001 or BL-1040. BL-1040 is an investigational, implantable medical device being studied for the prevention of heart failure following an acute myocardial infarction. The 303-patient, randomized, double-blinded, placebo-controlled study showed no statistically significant difference between patients treated with BCM versus placebo for both the primary and the secondary endpoints. BL-1040 was licensed to Bellerophon, known then as Ikaria, in 2009. Prior to partnering the project, BioLineRx invested slightly over US$ 10 million in the development of BL-1040. To date, BioLineRx has received a total of $17 million for this asset under the license agreement. Additional information on this study can be found at www.clinicaltrials.gov (ID: NCT01226563).

Cord Blood Registry

Cord Blood Registry (CA, USA; www.cordblood.com) has launched an FDA-regulated clinical trial to investigate autologous stem cell therapy in children diagnosed as having had a prenatal or perinatal pediatric stroke. To be conducted at the Florida Hospital for Children (FL, USA; www.floridahospital.com/children), the Phase 1 trial is the first to examine the use of newborn autologous stem cell therapy in the treatment of pediatric stroke. Following this trial, the goal is to develop Phase 2 studies that will further assess safety and measure efficacy in the use of stem cells to improve common symptoms of this condition. According to the American Stroke Association, a stroke occurs in about one in every 3,500 live births and is one of the leading causes of death in children between ages 1 and 19. Of children surviving a stroke, approximately 60 percent will have permanent neurological deficits, most commonly cerebral palsy and hemiparesis or hemiplegia — total or partial paralysis on one side of the body. Other long-term disabilities caused by a stroke occurring around the time of birth can include epileptic seizures, spasticity and bladder control issues. The risk of a stroke in children is greatest in the first year of life, and peaks during the perinatal period, roughly the weeks before and immediately after birth. Recruitment is underway to enroll 10 children between the ages of 6 weeks and 6 years who have experienced a stroke in utero or immediately after birth, and who have a CBR-processed cord blood unit, which was collected at birth. Subjects will first receive a baseline neurologic evaluation, which includes brain imaging, evaluation of epilepsy, nerve impulses, and bladder control issues, which will help assess the overall severity of the stroke’s impact prior to treatment. After this evaluation is complete, eligible patients will receive a single autologous stem cell infusion, with follow-up testing to occur after six and 12 months. Additional information on this study can be found at www.clinicaltrials.gov (ID: NCT02460484).

Mesoblast

Mesoblast (Australia; www.mesoblast.com) has published results of the Phase 2 trial of its intravenously delivered mesenchymal precursor cells (MPCs) therapy rexlemestrocel-L for the treatment of type 2 diabetes [1]. The Phase 2 randomized, single blind, placebo-controlled trial was conducted across 18 sites in the USA and evaluated the effects of a single intravenous infusion of 0.3, 1.0 or 2.0 million MPCs/kg or placebo over 12 weeks in 61 patients with a mean diabetes duration of 10 years. The treatment was safe and well tolerated with no immune responses against MPC donor HLA antigens identified in any subject. There was an improvement in glycemic control as evidenced by a decrease at all time points after week 1 in hemoglobin A1c (HbA1c) measurements in MPC-treated patients compared with an increase in HbA1c in placebo-controlled patients. The highest dose (2.0 million MPCs/kg) showed the greatest overall reduction in HbA1c, with a peak decrease of 0.4% at 8 weeks compared with placebo (p<0.05). The clinical target of good glycemic control, HbA1c <7%, was achieved by 5/15 (33%) subjects in the MPC 2.0 million/kg group vs. 0/15 (0%) in the placebo group, (p<0.05). Additional information on this study can be found at www.clinicaltrials.gov (ID: NCT01576328).

The company also published Phase 2 trial results of its cell therapy product candidate for the treatment of congestive heart failure [2]. Sixty patients were sequentially allocated into three dosing cohorts, 20 per dose-group. Each cohort was randomized to receive either mock procedure (n=5) or transendocardial injection of 25, 75, or 150 million MPCs (n=15). Safety and major adverse cardiac events (MACE) were evaluated for up to three years. The investigators found no differences between MPC-treated and control patients in survival probability, MACE-free probability, and all-cause mortality. However, heart failure-related MACE events were significantly reduced in the 150 million group (0/15) versus control (5/15; 33%), 25 million (3/15; 20%), and 75 million (6/15; 40%); the 150 million group differed significantly from all groups according to Kaplan-Meyer statistics over 3 years (P=0.025 for 150 million vs. control). Taken together the data suggest that transendocardial injections of allogeneic MPCs were feasible and safe in chronic heart failure patients and that high-dose allogeneic MPCs may provide benefits in this population. Additional information on this study can be found at www.clinicaltrials.gov (ID: NCT00721045).

References

1. Skyler JS, Fonseca VA, Segal KR, Rosenstock J; MSB-DM003 Investigators. Allogeneic mesenchymal precursor cells in type 2 diabetes: A randomized, placebo-controlled, dose escalation safety and tolerability pilot study. Diabetes Care Epub ahead of print (2015).

2. Perin EC, Borow KM, Silva GV et al. A Phase II Dose-Escalation Study of Allogeneic Mesenchymal Precursor Cells in Patients With Ischemic or Non-Ischemic Heart Failure. Circ. Res. Epub ahead of print (2015).