Industry Update: Clinical Trials

Written by Dusko ILIC

Latest developments compiled from 1 October until 30 November 2014

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 October until 30 November 2014, scheduled to be published in Volume 10 Issue 2 of Regenerative Medicine.


Beta-O2 (Israel; announced that the first patient participating in the company’s first broad study of the bAir Bio-Artificial Pancreas has been successfully implanted. Eight participants who meet the study criteria will be enrolled in the trial at Uppsala University Hospital in Sweden. In September 2014, JDRF ( awarded Beta-O2 a grant to fund half of the US$ 1 million, two-year, open label, pilot investigation, which will evaluate the safety and efficacy of implanting the bAir macro-encapsulation with human islets of Langerhans. The implant procedure took less than an hour. The patient remained hospitalized for four days thereafter for observation and was then discharged. Until day 180 following implantation, the patient will, among other protocol duties, be required to return to the clinic for monthly check-ups. On day 181, bAir will be explanted from the patient, who will continue to be followed for another 180 days. bAir is composed of an immune protection unit, 68 mm in diameter and 18 mm wide, connected to two ports, also implanted under the skin, just under and to the right of the naval. The encapsulation contains islets of Langerhans, with its main constituent the b-cells, which provide the insulin production in the body. Insulin is a hormone that is needed to transport sugar into cells, and thereby provide energy needed for daily life. Patients are to inject oxygen, once daily, into one of the two ports connected to the implant. This is done using bAir’s oxygenation system, which automatically measures and calculates the required amount of oxygen. Oxygen is essential for the survival of the enclosed b-cells as well as their ability to sense and produce the necessary quantity of insulin. Additional information about the clinical trial is available at (ID: NCT02064309), and


Cytori Therapeutics (CA, USA; reported the 6 months results from the first 20 patients enrolled in a clinical study of Cytori Cell Therapyâ„¢ in patients with anterior cruciate ligament tears. The procedure was feasible and not associated with safety issues above that seen with a standard small volume liposuction. All patients recovered without any complications. The results were compared to a historical control group of patients who had the same surgical procedure by the same surgical team but without other interventions. Overall, recovery from pain and ability to return to the field appeared to be accelerated as a result of the adipose-derived regenerative cells enriched bone-patellar tendon-bone transplant The patient questionnaires and serial magnetic resonance imaging scans of the knees following cell therapy were consistent with accelerated healing of the graft.


Geron Corporation (CA, USA; has launched a phase I clinical trial of a human embryonic stem cell (hESC)-based therapy for spinal cord injury (SCI) in October 2010 and stopped the trial just a year later after transplanting only 4 of the planned 10 patients. Two ethicists from the Center for Biomedical Ethics at Stanford University (CA, USA; discuss the prominent ethical and social questions raised by the Geron trial [3].


NeoStem (NY, USA; announced initial data from its 161 patient Phase 2 PreSERVE AMI (or acute myocardial infarction) clinical trial. PreSERVE AMI is a randomized, double-blind, placebo-controlled clinical trial of intracoronary infusion of autologous CD34 cells in patients with left ventricular dysfunction post-ST elevation myocardial infarction (STEMI). The trial included 161 subjects at 60 sites in the US, randomized 1:1 between treatment and placebo arms. Eligible patients presented with acute STEMI, had successful stenting of the infarct-related artery and had left ventricular dysfunction 4 days after AMI. Primary endpoints include occurrence of serious adverse events (SAEs) and major adverse cardiac events (MACE; defined as cardiovascular death, re-infarction, heart failure hospitalization, and coronary revascularization) through 3-year follow-up, occurrence of SAEs through 3-year follow-up, and 6-month change in myocardial perfusion (resting total severity score, RTSS) measured quantitatively by gated SPECT myocardial perfusion imaging. Other endpoints include cardiovascular magnetic imaging resonance to measure left ventricular ejection fraction, left ventricular end-systolic volume, left ventricular end-systolic diameter, regional myocardial strain, infarct/peri-infarct regional wall motion abnormalities and infarct size (baseline and 6-months) and quality of life measures. While all 6-month data has been collected, it is subject to ongoing analysis, and results reported at this time, although promising, are preliminary. There can be no assurance that further analysis may not reveal negative, or less promising, results.

Highlights of the initial results include:

·A statistically significant mortality benefit (p<0.05) in patients treated with NBS10 (also known as AMR-001) as compared to the placebo group; there were no deaths in the treatment group.

·A statistically significant dose-dependent reduction in SAEs (p<0.05).

·Observation of a dose-dependent numerical decrease in MACE. MACE occurred in 14% of control subjects, in 17% of subjects of who received less than 14 million CD34 cells, in 10% of subjects who received greater than 14 million CD34 cells, and in 7% of subjects who received greater than 20 million CD34 cells.

·When correcting for the time to stent implantation in all subjects, patients treated with CD34 cells were seen to have a statistically significant dose-dependent improvement in their ejection fraction (p<0.05). Independent from time to stent implantation, a statistically significant improvement in ejection fraction (p<0.05) for patients treated with a dose of greater than 20 million CD34 cells compared to placebo was observed.

·No meaningful difference in perfusion, as evidenced by SPECT imaging, between the treatment and the control group from baseline to 6 months in RTSS suggesting this may not be a future suitable tool to assess NBS10, which is consistent with US FDA guidance that mortality and MACE are the appropriate approvable endpoints to determine efficacy of a cellular therapy for cardiac disease as opposed to imaging endpoints.

Ocata (former Advanced Cell Technology)

Ocata Therapeutics (MA, USA;, formerly known as Advanced Cell Technology (MA, USA;, published Phase 1/2 clinical data demonstrating positive long-term safety results using their proprietary hESC-derived Retinal Pigment Epithelium cells for the treatment of Stargardt’s macular degeneration and dry age-related macular degeneration [4]. The publication features data from 18 U.S.-based patients with at least six months of post-transplant follow-up. Further information about company’s clinical trials are available at (ID: NCT01469832, NCT01345006 and NCT01344993).

In unrelated news, Ocata Therapeutics announced that it has been granted Advanced Therapy Medicinal Product (ATMP) designation for its Retinal Pigment Epithelium therapy for macular degeneration. This designation is an essential step in allowing companies to commercialize products effectively across the European Union.


StemCells (CA, USA; has initiated its Pathway® Study, a Phase II proof of concept clinical trial using its proprietary HuCNS-SC® platform of human neural stem cells for the treatment of cervical spinal cord injury (SCI). The Pathway Study is the first clinical study designed to evaluate both the safety and efficacy of transplanting stem cells into patients with traumatic injury to the cervical spinal cord. The trial will be conducted as a randomized, controlled, single-blind study and efficacy will be primarily measured by assessing motor function according to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). The primary efficacy outcome will focus on change in upper extremity strength as measured in the hands, arms, and shoulders. The trial will follow the patients for one year from the time of enrollment. Earlier this year, the Company completed enrollment in an open-label Phase I/II clinical trial in thoracic SCI (, ID: NCT01321333) and reported interim results from this trial on eight patients with at least six months of follow-up post transplantation. Half of the patients transplanted had significant post-transplant gains in sensory function. The interim results also continue to confirm the favorable safety profile of the cells and the surgical procedure. Based upon the strength of the interim data from its thoracic SCI study, the Company made the decision to move forward with the first in human clinical trial to assess the efficacy of stem cell transplants for the treatment of cervical SCI. The first site initiated into the Pathway Study is the University of Miami Miller School of Medicine, home to The Miami Project To Cure Paralysis ( Additional information about the clinical trial is available at and (ID: NCT02163876).


The first patient was successfully implanted with VC-01â„¢ in Viacyte’s (CA, USA; Phase 1/2 study designed to evaluate the VC-01 product candidate directly in patients with type 1 diabetes. VC-01 product candidate delivers hESC-derived pancreatic precursor cells (called PEC-01â„¢ cells) that are designed to further differentiate and mature after surgical implantation, not only to fully functioning insulin-producing beta cells, but also to other endocrine cell types that make up the normal human pancreatic islet. Thus, along with the critically important insulin, the implanted cells are expected to produce other hormones that are important for the regulation of glucose (sugar) in the blood, including, for example, glucagon, somatostatin, and amylin. The PEC-01 cells are delivered under the skin in a proprietary device with a selectively porous cell-impermeable membrane, called the Encaptra® drug delivery system. The Encaptra device is designed to protect the implanted cells from possible immune rejection, to permanently contain the cells and prevent their distribution away from the implantation site, and to provide a platform for product vascularization. The ongoing Phase 1/2 clinical trial is evaluating the VC-01 product candidate directly in patients with type 1 diabetes who have minimal to no insulin-producing b-cell function. In addition to determining the safety of the product candidate in these patients, the study is designed to evaluate the effectiveness of the VC-01 product candidate in replacing the lost endocrine function that is central to the disease. In an open-label, dose-escalating format, ViaCyte expects to enroll approximately 40 patients in the study at multiple clinical sites. Further information about this clinical trial are available at (ID: NCT02239354).


[3]Scott CT, Magnus D. Wrongful termination: lessons from the Geron clinical trial. Stem Cells Transl. Med. 3(12), 1398-1401 (2014).

[4]Schwartz SD, Regillo CD, Lam BL et al. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy: follow-up of two open-label phase 1/2 studies. Lancet. pii: S0140-6736(14)61376-3 (2014).