RANCHO CORDOVA, Calif., June 01, 2016 (GLOBE NEWSWIRE) -- Cesca Therapeutics Inc. (NASDAQ:KOOL), an autologous cell-based regenerative medicine company, today announced that the Company has submitted an Investigational Device Exemption (IDE) Supplement to the U.S. Food and Drug Administration (FDA) for its previously approved pivotal trial for the treatment of patients with critical limb ischemia (CLI), using the Company’s SurgWerksTM system. The Company expects the FDA to submit its response to the IDE supplement within 30 days of submission.
After careful review of both current literature and data available from earlier studies, and in conjunction with expert independent advisors, the Company concluded that Amputation-Free Survival (AFS) would not be a practical primary endpoint for a successful pivotal trial. Limb revascularization procedures are not specifically intended to improve survival and, as a result, endpoints that couple limb-related outcomes with all-cause mortality over time (such as Amputation Free Survival) are inherently compromised as specific measures of the effectiveness of revascularization. The Company concluded that adequately powering a study using AFS as the primary endpoint would be prohibitively time consuming and costly and that adequate statistical power could only be practically generated if data was produced from every treated limb.
Alternative endpoints considered included (i) Clinically Meaningful Endpoints such as Complete Wound/Ulcer Healing and the 6 Minute Walk Test, (ii) Patient Reported Outcome Measures such as Rest Pain and Quality of Life, and (iii) Surrogate Endpoints such as Ankle Brachial Index, Toe Brachial Index, Transcutaneous Oxygen Pressure, Hyperspectral Imaging, Skin Perfusion Pressure and Blood Oxygenation Level dependent MRI.
In the supplement, the Company proposed Transcutaneous Oxygen Pressure (TcPO2) as a surrogate endpoint. TcPO2 is a non-invasive, clinically-accepted method for measuring the amount of oxygen diffused from capillaries through the skin, and reflects both the oxygen supply and the metabolic demand in a specific region. The Company believes that ample clinical evidence exists to support the claim that (i) TcPO2 predicts the risk of major amputation, (ii) endovascular interventions, including cell therapy, increase (improve) TcPO2 values, and (iii) cell therapy significantly reduces the risk of major amputation.
The revised Phase III trial design will focus on the mean difference in TcPO2 measured at 12 months between a treatment arm and a control arm. The general design of the study will include 3:1 randomization, a 12 month follow-up program, and Rutherford category 5 CLI patients. The estimated sample size needed to successfully demonstrate safety and a statistically powered efficacy result is 148 patients (100 patients in the treatment arm, 33 patients in the control arm with a further 10% assumed to cover dropouts).
The supplement also details changes to the protocol that are expected to improve both patient enrollment and study flow. These include expanding the cohort to include both “no option” and “poor option” CLI patients, removing unnecessary patient testing requirements, improving the mapping and injection procedure, and eliminating the Blinded Independent Review Committee for enrollment and endpoint analysis. The supplement also expands the number of secondary endpoints and extends the follow-up period beyond an observational phase to facilitate collection of additional data in support of reimbursement from The Centers for Medicare and Medicaid Services (CMS).
“We believe that the submission of this IDE supplement for our pivotal trial for the treatment of CLI patients with SurgWerksTM is highly significant,” said Robin Stracey, Cesca’s Chief Executive Officer. “The change in primary endpoint and the proposed amendments to the protocol dramatically improve the probability of a successful outcome compared to past trial designs. The historical reliance on AFS as a clinical endpoint has prohibited new regenerative technologies from having an achievable pathway to regulatory approval. If cell or gene-based therapies are to be available to US physicians, an alternative endpoint has to be used for establishing efficacy. We look forward to working with the FDA throughout the review process and will continue to provide updates in the coming weeks.”
About Cesca Therapeutics Inc.
Cesca Therapeutics Inc. (www.cescatherapeutics.com) is engaged in the research, development, and commercialization of cellular therapies and delivery systems for use in regenerative medicine. The Company is a leader in the development and manufacture of automated blood and bone marrow processing systems that enable the separation, processing and preservation of cell and tissue therapeutics. These include:
- The SurgWerks™ System (in development) - a proprietary system comprised of the SurgWerks Processing Platform, including devices and analytics, and indication-specific SurgWerks Procedure Kits for use in regenerative stem cell therapy at the point-of-care for vascular and orthopedic diseases.
- The CellWerks™ System (in development) - a proprietary cell processing system with associated analytics for intra-laboratory preparation of adult stem cells from bone marrow or blood.
- The AutoXpress® System (AXP®) - a proprietary automated device and companion sterile disposable for concentrating hematopoietic stem cells from cord blood.
- The MarrowXpress™ System (MXP™) - a derivative product of the AXP and its accompanying sterile disposable for the isolation and concentration of hematopoietic stem cells from bone marrow.
- The BioArchive® System - an automated cryogenic device used by cord blood banks for the cryopreservation and storage of cord blood stem cell concentrate for future use.
- Manual bag sets for use in the processing and cryogenic storage of cord blood.
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Source:Cesca Therapeutics Inc.