Industry Update: Clinical trials

Latest developments compiled from 01 — 31 January 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 01 — 31 January 2015, scheduled to be published in Volume 10 Issue 4 of Regenerative Medicine.

Bellicum

Bellicum Pharmaceuticals (TX, USA; www.bellicum.com) announced that the first cohort of patients in the BP-004 trial has completed dosing with the Company’s genetically engineered donor T cells (BPX-501), after receiving a partial T depleted haploidentical allogeneic hematopoietic stem cell transplant (haplo-HSCT). The trial in pediatric patients is evaluating whether BPX-501 T cells from partially mis-matched donors administered following HSCT are safe and can help speed immune reconstitution. BPX-501 contains the CaspaCIDe® safety switch, giving doctors the ability to eliminate the T cells should they cause Graft-versus-host disease (GvHD), a more common occurrence with a haplo-HSCT than with a matched procedure. BPX-501 is designed to allow study doctors to restore patient immunity earlier with increasingly higher doses of haplo-identical T cells, in an effort to improve infection control and overall transplant outcomes.

The Phase 1 arm consists of three cohorts of 3-6 patients, each receiving escalating doses of BPX-501 T cells following haplo-HSCT. A Phase 2 extension arm will use the highest tolerated Phase 1 dose, with a maximum of 30 patients in both phases. The trial is enrolling pediatric patients, ages three months to 21 years, diagnosed with blood cancers, immune deficiencies or inherited hematologic disorders, where HSCT are historically curative. The trial will also evaluate the treatment of GvHD in transplant patients who have received BPX-501 by infusion of the small molecule, dimerizer drug rimiducid (formerly AP1903). Rimiducid is designed to trigger rapid apoptosis and elimination of allo-reactive T cells. Patients who develop Grade III-IV acute GvHD, Grade II gut/liver GvHD, or Grade I-II acute GvHD (skin only) who progress or do not respond to standard treatment, will receive rimiducid. Primary study endpoints include safety and optimal dosing of BPX-501 T cells, safety of rimiducid infusion in those patients who receive it to trigger elimination of BPX-501 T cells, and time to immune reconstitution. Primary endpoints for the Phase 2 extension also includes cumulative incidence of non-relapse mortality at 180 days and one year. Additional information about the clinical trial is available at http://clinicaltrials.gov (ID: NCT01744223)

BioLineRx

BioLineRx (Israel; www.biolinerx.com) has completed the dose escalation stage of a Phase 1 trial for its novel oncology platform, BL-8040, as a novel treatment for the mobilization of stem cells from the bone marrow to the peripheral blood circulation. All healthy volunteers completed the treatment phase and results are expected within 2015. The Phase 1 study consists of two parts. The first part is a randomized, double blind, placebo-controlled dose escalation study exploring the safety and tolerability of escalating repeated doses of BL-8040 in healthy volunteers. Secondary objectives include assessment of the efficacy of BL-8040 in mobilizing stem cells as a stand-alone therapy, as well as determining the pharmacodynamic and pharmacokinetic profile of the drug. This part was performed in three cohorts, with eight healthy volunteers in each cohort. Following analysis of the data, the optimal safe and efficacious dose of BL-8040 will be selected for use as a stand-alone therapy in the second part of the study. The second part of the study is an open-label study designed to assess BL-8040’s stem cell mobilization capacity, as well as the yield of cells collected by apheresis. Secondary endpoints of the study include evaluation of the viability and biological activity of cells mobilized by BL-8040 and collected by apheresis. This part will be performed in a single cohort of eight healthy volunteers who will receive the selected dose regimen of BL-8040 based on the data from the first part of the study. Additional information about the clinical trial is available at http://clinicaltrials.gov (ID: NCT02073019)

Bone Therapeutics

Bone Therapeutics (Belgium; www.bonetherapeutics.com) announced positive efficacy results for the first cohort of four patients enrolled in the Phase I/IIA delayed-union trial with its allogeneic bone-forming cell product ALLOB®. Results from the initial four patients showed that all four ALLOB-treated patients met the primary endpoints of the study and three patients have completely healed. The ongoing Phase I/IIA study is a six month open-label trial to evaluate the safety and efficacy of ALLOB in the treatment of delayed-union fractures of long bones. In the first cohort of four patients with a fracture that had not consolidated after a minimum of three and a maximum of seven months each patient has received a single percutaneous administration of ALLOB directly into the fracture site. Fracture healing of ALLOB-treated patients is assessed in comparison to baseline at two weeks, one, three and six months using clinical (e.g., pain, weight bearing) and radiological evaluation. Treatment success will have been achieved when the health status of the patient has improved by at least 25% and the radiological score, as assessed by CT scan, has increased by at least two points versus baseline. Additional information about the clinical trial is available at http://clinicaltrials.gov (ID: NCT02020590).

BrainStorm

Brainstorm Cell Therapeutics (Israel; www.brainstormcell.com) announced positive final results from its phase 2a clinical trial of NurOwnâ„¢ in amyotrophic lateral sclerosis (ALS) patients, which enrolled 14 subjects at Hadassah Medical Center in Jerusalem. The study achieved its primary endpoint in demonstrating that NurOwnâ„¢ is safe and well-tolerated at doses up to 2 million cells per kilogram administered intrathecally (IT) and 48 million cells administered intramuscularly (IM). The study enrolled 14 early-stage ALS patients into three ascending dose cohorts; each subject received NurOwn cells via IT and IM administration after a three-month run-in period, and was then followed for six additional months after treatment. Subjects in this study were assessed at monthly visits by ALS Functional Rating Score-Revised (ALSFRS) and for respiratory function by forced vital capacity (FVC). The rate of decline for these measures was determined by calculating the slope of the linear regression line for the run-in period, the three-month follow-up period, and the six-month follow-up period. On ALSFRS, NurOwn slowed the rate of progression by 45%, from 1.41 points per month during the run-in period to 0.78 points per month for the three months following treatment, and by 57% to 0.60 per month for the six months following treatment. NurOwnâ„¢ had a similarly strong effect on the progressive loss of lung function — the rate of decline in percent-predicted FVC was reduced by 73%, from an average of 2.60% per month during the run-in period to just 0.70% per month for the three months after treatment, and by 67% to 0.86% per month for the six months following treatment. Additional information about the clinical trial is available at http://clinicaltrials.gov (ID: NCT01777646).

INSERM

On the 21 October 2014, Professor Philippe Menasché and his team from the cardiovascular surgery service of the Georges Pompidou European Hospital, AP-HP (France; www.aphp.fr/hopital/hegp), carried out a transplant of cardiac cells derived from hESC, according to a method developed by the Department of Cell and Tissue Biotherapies of the Saint-Louis hospital, directed by Professor Jérôme Larghero and through research led by this group within Inserm. The surgery, coupled with a coronary bypass, was carried out on a woman of 68 years suffering from severe heart failure. Ten weeks after the intervention, the patient is feeling well, her condition has improved markedly, with no complications having been observed.