Industry Update: Clinical trials
Latest clinical trial developments compiled from March 01 — 31, 2016.
Latest business developments in the field of stem cell research and
regenerative medicine compiled from publicly available information and
press releases from non-academic institutions from March 01 — 31 2016, scheduled to be published in Volume 11 Issue 5 of Regenerative Medicine.
BioLineRx
BioLineRx (Israel; www.biolinerx.com) has initiated a Phase 2 trial for BL-8040, a C-X-C chemokine receptor type 4 (CXCR4) antagonist, as a novel approach for the mobilization and collection of bone marrow stem cells from the peripheral blood circulation. The Phase 2 open-label study will be conducted in collaboration with the Washington University School of Medicine, Division of Oncology and Hematology (MO, USA; http://oncology.wustl.edu), and will enroll up to 24 donor/recipient pairs, aged 18-70. The trial is designed to evaluate the ability of BL-8040, as a single agent, to promote stem cell mobilization for allogeneic transplantation. On the donor side, the primary endpoint of the study is the ability of a single injection of BL-8040 to mobilize sufficient amounts of cells for transplantation following up to two leukapheresis collections. On the recipient side, the study aims to evaluate the functionality and engraftment following transplantation of the BL-8040 collected graft. The study will also evaluate the safety and tolerability of BL-8040 in healthy donors, as well as graft durability, the incidence of grade 2-4 acute graft versus host disease (GvHD), and other recipient related parameters in patients who have undergone transplantation of hematopoietic cells mobilized with BL-8040.
In an independent press release, BioLineRX announced positive top-line results from BL-8040’s Phase 2 clinical trial in relapsed or refractory acute myeloid leukemia (r/r AML). Results of the Phase 2 clinical trial showed that BL-8040, as a single agent and in combination with Cytarabine (Ara-C), was safe and well tolerated at all doses tested up to and including the highest dose level of 2.0 mg/kg, with no major adverse events (n=45). The composite complete remission rate, including both complete remission (CR) and complete remission with incomplete blood count recovery (CRi), was 38% in subjects receiving up to two cycles of BL-8040 treatment at doses of 1 mg/kg and higher (n=39). Patients included in the study were patients that had undergone a significant number of prior treatments or that were refractory to induction treatment.
Capricor
California Institute for Regenerative Medicine (CA, USA; www.cirm.ca.gov) has approved a grant award to Capricor Therapeutics (CA, US; www.capricor.com)for approximately US$ 3.38 million to support the Company’s Phase I/II HOPE-Duchenne (Halt cardiomyOPathy progrEssion in Duchenne) clinical trial investigating CAP-1002, a cardiac cell therapy, in patients with Duchenne muscular dystrophy-associated cardiomyopathy. CAP-1002, Capricor’s lead product candidate, is an allogeneic, intracoronary-delivered, cardiosphere-derived cell treatment. This investigational therapy is an “off-the-shelf” cell therapy which comes from donor heart tissue and is infused directly into a patient’s coronary artery during a catheterization procedure. CAP-1002 received orphan drug designation from the US FDA for the treatment of Duchenne muscular dystrophy. The award was granted under the CIRM 2.0 program, a comprehensive collaborative initiative designed to accelerate the development of stem cell-based treatments for people with unmet medical needs. Capricor also reported the completion of enrollment of the pre-specified first patient cohort in the HOPE-Duchenne trial. Additional information about this clinical trial is available at http://clinicaltrials.gov (ID: NCT02485938).
Immunocore
Immunocore (UK; www.immunocore.com) has recruited the first patient into a Phase I monotherapy trial of its lead program, IMCgp100, for the treatment of uveal melanoma. The trial will include three Phase I escalation cohorts to determine the optimal dose for the pivotal Phase II study, which is expected to start in 2016, and will take place at a number of leading centers around the world. In January 2016, the US FDA granted Orphan Drug Designation to IMCgp100 for the treatment of uveal melanoma. IMCgp100 is Immunocore’s wholly-owned and most advanced Immune Mobilizing Monoclonal T-Cell Receptor Against Cancer (ImmTAC), currently in Phase I/IIa clinical trials for the treatment of late stage metastatic melanoma. Promising results from the Phase I/IIa clinical trial of IMCgp100 in advanced cutaneous and uveal melanoma patients demonstrated that responses were durable, with five objective responses to date, two of which are partial responders in patients with uveal melanoma. To date, more than 85 patients have been treated with IMCgp100. Additional information about this clinical trial is available at http://clinicaltrials.gov (ID: NCT02570308).
Osiris
Osiris Therapeutics (MD, USA; www.osiris.com) announced the results of its prospective, multi-center, single-arm clinical trial evaluating the clinical outcomes of Grafix® in patients with complex chronic diabetic foot ulcers with exposed tendon and bone. Grafix is a cryopreserved placental membrane intended to be used as a wound cover for patients suffering from chronic wounds. A total of 31 patients were enrolled, 27 of whom completed the protocol. The patient group had significant co-morbidity, with over 80% having hypertension, over 60% being current or former smokers, 55% having heart disease and 45% having had a previous partial amputation. The mean wound area at baseline was 14.6 cm2, all wounds were present for at least 4 weeks with a mean wound duration of 7.5 months. The proportion of patients meeting the primary end-point of complete (100%) granulation at 16 weeks was 96.3%. The mean time to 100% granulation was 6.8 weeks with a mean of 6.8 applications of Grafix. The proportion of patients meeting the secondary endpoint of complete (100%) wound closure at 16 weeks was 59.3%, whereas the mean percentage area reduction of all wounds at 16 weeks was 92.3%. There were no Grafix-related adverse events recorded. Additional information about this clinical trial is available at http://clinicaltrials.gov (ID: NCT02260609).
TiGenix
TiGenix (Belgium; www.tigenix.com) has presented 24-week results from the Phase III ADMIRE-CD pivotal trial of Cx601 for complex perianal fistulas in Crohn’s disease patients, in a plenary session at the 11th Annual Congress of the European Crohn’s and Colitis Organisation (ECCO; www.ecco-ibd.eu) in Amsterdam, The Netherlands. ADMIRE-CD is a randomized, double-blind, placebo-controlled, Phase III study, designed to investigate the efficacy and safety of a single injection of Cx601 for the treatment of complex perianal fistulas in Crohn’s disease patients. Cx601 is a suspension of allogeneic, expanded, adipose-derived stem cells for intralesional injection. A single injection of Cx601 achieved statistically significant superiority vs. placebo in the primary efficacy endpoint of combined remission at week 24 (defined as clinical assessment of closure of all treated external openings draining at baseline, despite gentle finger compression, and absence of collections >2cm confirmed by MRI; p=0.024). This definition of remission is more stringent than those commonly used in clinical trials on perianal fistulizing disease, as it includes both clinical and radiological assessment by MRI.
In parallel, independently of ECCO meeting, the company announced that a single injection of Cx601 was statistically superior to placebo in achieving combined remission at week 52 in the treatment of complex perianal fistulas in Crohn’s disease patients with inadequate response to previous therapies: 54.2% of patients treated with Cx601 achieved combined remission at week 52 compared to 37.1% in the placebo arm. Additionally, 75.0% of Cx601 treated patients who achieved combined remission at week 24 remained in combined remission at week 52 compared to only 55.9% in the placebo arm. The results confirm the favorable safety and tolerability profile of Cx601 already reported at week 24.
Vericel
Vericel Corporation (MA, USA; www.vcel.com) released results from the company’s Phase 2b ixCELL-DCM clinical trial of ixmyelocel-T in patients with advanced heart failure due to ischemic dilated cardiomyopathy (DCM). Ixmyelocel-T is a patient-specific, expanded multicellular therapy manufactured from the patient’s own bone marrow using Vericel’s proprietary, highly automated, fully closed cell-processing system. This process selectively expands the population of mesenchymal stromal cells and alternatively activated macrophages, which are responsible for production of anti-inflammatory and pro-angiogenic factors known to be important for repair of damaged tissue. Ixmyelocel-T has been designated as an orphan drug by the US FDA for use in the treatment of DCM. The Phase 2b ixCELL-DCM clinical trial is a multicenter, randomized, double-blind, placebo-controlled Phase 2b study designed to assess the efficacy, safety and tolerability of ixmyelocel-T compared to placebo when administered via transendocardial catheter-based injections to subjects with end-stage heart failure due to ischemic DCM, who have no reasonable revascularization options, either surgical or percutaneous interventional, likely to provide clinical benefit. The trial was designed to provide approximately 80% power to show a 46% difference in cardiac events for ischemic DCM patients treated with ixmyelocel-T compared to placebo. A total of 114 patients were treated in the ixCELL-DCM clinical trial at 28 sites in the USA. The trial met its primary endpoint of demonstrating a reduction in the total number of deaths, cardiovascular hospitalizations or unplanned outpatient and emergency department visits to treat acute decompensated heart failure during the 12 months following treatment with ixmyelocel-T compared to placebo.All clinical events in the primary and secondary endpoints were adjudicated in a blinded fashion by an independent adjudication committee. The incidence of adverse events, including serious adverse events, in patients treated with ixmyelocel-T was comparable to patients in the placebo group. Additional information about this clinical trial is available at http://clinicaltrials.gov (ID: NCT01020968).