Industry Update: Clinical trials

Latest clinical trial developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from non-academic institutions June 01 — June 30, 2017.

Latest clinical trial developments compiled from June 01 — June 30, 2017, scheduled to be published in Volume 12 Issue 7 of Regenerative Medicine.

Asterias

Asterias Biotherapeutics (CA, USA; www.asteriasbiotherapeutics.com) has announced that new 9-month follow-up data from the AIS-A 10 million cell cohort in the company’s ongoing SCiStar Phase 1/2a clinical trial (https://clinicaltrials.gov : NCT02302157; www.SCiStar-study.com) shows three of six (50%) patients have now achieved two motor levels of improvement over baseline on at least one side and previously-announced improvements in arm, hand and finger function at 3-months and 6-months following administration of AST-OPC1. All six patients (100%) achieved at least one motor level of improvement on at least one side. Improvements in upper extremity motor function are being measured using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) scale, widely used to quantify functional status of patients with spinal cord injuries. The SCiStar trial is an open-label, single-arm trial testing three sequential escalating doses of AST-OPC1 administered at up to 20 million AST-OPC1 cells in as many as 35 patients with sub-acute, C-5 to C-7, motor complete (AIS-A or AIS-B) cervical SCI. These individuals have essentially lost all movement below their injury site and experience severe paralysis of the upper and lower limbs. AIS-A patients have lost all motor and sensory function below their injury site, while AIS-B patients have lost all motor function but may retain some minimal sensory function below their injury site. AST-OPC1 is being administered 14 to 30 days post-injury. The study is being conducted at six centers in the U.S. and the company plans to increase this to up to 12 sites to accommodate the expanded patient enrollment.

BioTime

BioTime (CA, USA; www.biotimeinc.com) has reported that, based on the analysis of top line data, the Renevia® pivotal trial in Europe has met its primary endpoint. The primary endpoint was the change in hemifacial volume at six months in the treated patients compared to patients in the delayed treatment arm as measured by 3D photographic volumetric assessment. Treated patients received approximately 5cc of Renevia in each side of the face. On average, 5.1cc of hemifacial volume was measured after six months, which represents an approximate 100% retention of transplanted volume. Untreated patients had no incremental hemifacial volume after six months. Comparison of the two trial arms had a statistical p value <.001. All Renevia transplants were shown to be safe and well tolerated. There were no serious adverse events during the trial. Renevia is an investigational medical device that is being developed as a replacement for whole adipose tissue in cell assisted lipotransfer (CAL) procedures. Renevia’s hydrogel polymer network provides the requisite amino acid sequences for adipose stromal vascular cell attachment and may support proliferation, localization and adipogenic differentiation. Renevia is part of the HyStem hydrogel family of proprietary injectable matrices, which are designed to facilitate the survival and growth of transplanted cells.

Cellectis

Cellectis (NY, USA; www.cellectis.com) has announced the first administration in the Phase I clinical study in Acute Myeloid Leukemia (AML) for its investigational product UCART123, one of the Company’s wholly-controlled TALEN® gene-edited product candidates. This marks the first allogeneic, “off-the-shelf” gene-edited CAR T-cell product candidate targeting CD123 to be investigated in clinical trials.

Histogenics

Histogenics (MA, USA; www.histogenics.com) has completed patient enrollment of its NeoCart (www.neocartimplant.com) Phase 3 clinical trial in accordance with the Special Protocol Assessment (SPA) agreement with the US FDA. Histogenics expects to report 1-year data in the third quarter of 2018, followed by a potential Biologics License Application (BLA) filing. The randomized Phase 3 clinical trial is designed to evaluate the safety and efficacy in 245 patients, of NeoCart compared to microfracture, the current standard of care for the treatment of articula cartilage defects. The primary endpoint of the trial is a dual-threshold responder analysis measuring the improvement in the pain and function of each patient treated with NeoCart compared to those treated with microfracture one year after treatment. The Phase 3 clinical trial design and primary endpoint is based on Histogenics’ 30-patient Phase 2 clinical trial that demonstrated highly statistically significant superiority results of NeoCart compared to microfracture at one year.

Juno

Juno Therapeutics, Inc. (NASDAQ: JUNO), a biopharmaceutical company developing innovative cellular immunotherapies for the treatment of cancer, today presented data from the TRANSCEND trial of JCAR017 in relapsed and refractory (r/r) aggressive B cell non-Hodgkin lymphoma (NHL; https://clinicaltrials.gov : NCT02631044). JCAR017 is Juno’s investigative chimeric antigen receptor (CAR) T cell product candidate that targets CD19, a protein expressed on the surface of almost all B cell malignancies, and uses a defined composition of CD4 to CD8 T cells and a 4-1BB costimulatory domain, which differentiates it from other current CD19-directed CAR T product candidates. JCAR017 has been granted Breakthrough Therapy designation by the FDA for treatment of r/r aggressive large B cell NHL and PRIME designation by the European Medicines Agency for treatment of r/r diffuse large B cell lymphoma (DLBCL), a type of NHL. A Phase 1 study that has treated a total of 67 patients with r/r aggressive B cell NHL, including those with DLBCL or follicular lymphoma grade 3B, as of a data cutoff date of May 4, 2017. TRANSCEND NHL 001 is a dose-finding study of JCAR017, which is administered following fludarabine/cyclophosphamide lymphodepletion. Patients received one of two dose levels (50 or 100 million cells). They were then evaluated for pharmacokinetics, disease response, and safety outcomes, including common CAR T side effects such as cytokine release syndrome (CRS) and neurotoxicity (NT). Early data do not suggest a dose toxicity relationship at the doses tested. The most frequently reported treatment-emergent adverse events were neutropenia (35%), CRS (35%), and fatigue (31%).

Kite Pharma

Kite Pharma (CA, USA; www.kitepharma.com) has announced that 73% of patients achieved complete remission, including those with incomplete or partial recovery of bone marrow, in an updated analysis of the Phase 1 ZUMA-3 trial of KTE-C19 in adults with high burden relapsed/refractory acute lymphoblastic leukemia (r/r ALL; https://clinicaltrials.gov : NCT02614066). All responders tested negative for minimal residual disease (MRD). Kite’s lead product candidate KTE-C19, also known as axicabtagene ciloleucel, is an investigational therapy in which a patient’s T cells are engineered to express a CAR to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T cells to kill cancer cells. KTE-C19 has been granted Breakthrough Therapy Designation status for DLBCL, transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL) by the US FDA and Priority Medicines (PRIME) regulatory support for DLBCL in the EU.

Mallinckrodt

Mallinckrodt (UK; www.mallinckrodt.com) has confirmed enrollment of the first patient in the company’s Phase 3 study (https://clinicaltrials.gov : NCT03005106) assessing the efficacy and safety of StrataGraft regenerative skin tissue in the promotion of autologous skin regeneration of complex skin defects due to thermal burns that contain intact dermal elements. The study will include patients with 3-49% total body surface area complex skin defects due to thermal burns with intact dermal elements for which excision and autografting are clinically indicated. This project has been funded in whole or in part with federal funds from the Biomedical Advanced Research and Development Authority (BARDA; www.phe.gov/about/barda/Pages/default.aspx).

Sentien

Sentien Biotechnologies, Inc., has opened enrollment in its Phase 1/2 trial of SBI-101 for adult patients with acute kidney injury (AKI; https://clinicaltrials.gov : NCT03015623). This trial is Sentien’s first clinical program. SBI-101 is a combination product that combines mesenchymal stromal cells (MSCs) within a blood-filtration device, allowing for controlled, dynamic interaction of MSCs with a patient’s bloodstream. SBI-101 offers two major advantages over traditional, intravenous cell therapy: (1) The duration of cell therapeutic bioactivity is significantly extended by maintaining the MSCs outside the body, in an extracorporeal device; and (2) the MSC cell dose can be increased beyond intravenous limits because the cells are immobilized in the device. To treat AKI, SBI-101 integrates seamlessly into a continuous renal replacement therapy (CRRT) circuit, thereby providing patients with both standard-of-care and MSC-mediated blood conditioning in a single session. The primary objective of the trial is to evaluate the safety and tolerability of SBI-101 in patients with AKI. Endpoints for efficacy and pharmacodynamic responses to SBI-101 therapy will also be evaluated. Patient recruitment is expected to continue into 2018, with an estimated enrollment of 24 patients.