Industry update: clinical trials
Latest clinical trial developments compiled from 1 April—31 May 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 April—31 May 2015, scheduled
to be published in Volume 10 Issue 6 of Regenerative Medicine.
Athersys
Athersys (OH, USA; www.athersys.com) announced interim results from its exploratory Phase 2 clinical study of the intravenous administration of MultiStem® cell therapy to treat patients who have suffered an ischemic stroke. The study results demonstrate favorable safety and tolerability for MultiStem, consistent with prior studies. With respect to the primary and secondary endpoints, the cell therapy did not show a difference at 90 days compared to placebo. However, MultiStem treatment was associated with lower rates of mortality and life threatening adverse events (AEs), infections and pulmonary events. Furthermore, post-hoc analysis shows that patients who received MultiStem treatment earlier in the treatment window had more robust recovery rates in comparison to placebo and relative to patients who received later MultiStem treatment. The randomized, double-blind, placebo-controlled Phase 2 clinical trial is being conducted at sites in the US and the UK. The study was conducted in two parts – a small dose selection phase, involving 16 patients in two cohorts, followed by larger efficacy phase of 118 patients. The evaluable patient population included 8 patients from cohort 2 and the cohort 3 patients, which all received a high dose of treatment or placebo. The study enrolled subjects who received either MultiStem treatment or placebo one to two days following the stroke. The primary endpoints for the study include safety over the first seven days following treatment and global stroke recovery at day 90, which assesses disability (modified Rankin Score ≤2) neurological deficit (NIG stroke scale, delta ≥75%) and activities of daily living (Barthel Index ≥95%). Additionally, there are secondary and exploratory endpoints evaluating elements of recovery and dysfunction, including biomarkers associated with subject condition and recovery, and safety variables over the study period. Of the patients evaluated in the study, 65 patients were in the MultiStem treatment group and 61 patients were in the placebo group. Further information about this clinical trial are available at http://clinicaltrials.gov (ID: NCT01436487).
Bellicum
Bellicum Pharmaceuticals (TX, USA; www.bellicum.com) has published the clinical results from a study using the Company’s Caspase-9 safety switch CaspaCIDe [1]. The study assessed immune reconstitution, safety and anti-viral response in patients undergoing T cell-depleted, haploidentical hematopoietic stem cell transplant (haplo-HSCT), followed by administration of donor T cells that were engineered with CaspaCIDe. Twelve patients undergoing haplo-HSCT to treat blood cancers were treated in dose escalating cohorts with donor T cells engineered with the CaspaCIDe safety switch. The engineered T cells were infused 30 to 90 days following stem cell transplant. Patients were monitored for safety, immune reconstitution and ability of transplanted T cells to fight viral infections. Rimiducid was infused in patients presenting with confirmed Grade I or II Graft vs. Host Disease (GvHD). Four of the 12 patients developed acute GvHD, and all were successfully treated with rimiducid with no GvHD recurrence. Results also showed that the transplanted engineered T cells provided rapid protection from the viruses EBV, CMV, VZV, HHV6, and BKV. Although administration of rimiducid resulted in a temporary reduction in circulating virus-specific T cells, those cells subsequently recovered and anti-viral activity was maintained.
Based on the encouraging findings from the Phase 2 study, Caladrius (NY, USA; www.caladrius.com) designed a randomized, double blind, placebo-controlled Phase 3 trial to confirm the benefit of CLBS20 (formerly known as NBS20) in patients with recurrent Stage III or Stage IV metastatic melanoma. The Phase 3 trial has been granted Special Protocol Assessment stating that the Phase 3 clinical trial is adequately designed to provide the necessary data that, depending on outcome, could support a Biologics License Application seeking marketing approval of CLBS20. CLBS20 has received Fast Track and Orphan Drug designation by the US FDA as well as Advanced Therapeutic Medicinal Product classification by the European Medicines Agency (EMA). The first patient for this study was randomized in April 2015, and enrollment is targeted for completion by Q4 of 2016. Interim analysis of the data is targeted in Q4 of 2017. The study will enroll 250 patients in 60 cities in the US, Canada, Australia and New Zealand. CLBS20 are autologous dendritic cells loaded with antigens from autologous cancer-initiating cells. Further information about this clinical trial are available at http://clinicaltrials.gov (ID: NCT01875653).
Reference
[1] Zhou X, Dotti G, Krance RA et al. Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation. Blood (Epub ahead of print) (2015).