Clinical Trials

Cytori Therapeutics’ clinical development program consists of rigorous, well-designed, controlled studies targeted to clinical indications with high medical needs inadequately addressed by currently available therapeutic options. As a part of clinical data acquisition with Cytori Cell TherapyTM we also support promising investigator initiated studies.

Adipose-based therapeutic formulations are derived from ADRCs and specifically adapted to individual indications or clinical situations. For example, formulation ECCS-50 has been developed for the treatment of rheumatologic diseases such as scleroderma and the associated hand dysfunction.


Scleroderma:

Cytori has received approval to begin the STAR Trial, a randomized, double blind, placebo-controlled, Phase III pivotal clinical trial of 80 patients with impaired hand function from scleroderma in up to 12 US sites. The trial will evaluate the one-year safety and efficacy of a single administration of Cytori Cell Therapy: ECCS-50 in patients with scleroderma affecting the hands. More than 90 percent of scleroderma patients have hand involvement, which is typically progressive with substantial pain, blood flow changes, and severe dysfunction. The primary endpoint of the study is the Cochin Hand Function Score—a validated measure of hand function—measured six months after a single administration of ECCS-50 or placebo. Other key efficacy endpoints include assessments of Raynaud’s Phenomena and health-related quality of life. After all patients have completed 48 weeks of follow up, patients in the placebo group will be eligible for crossover to the active arm of the trial. The trial is anticipated to begin enrollment in 2015.

This trial is based on the previously published trial, SCLERADEC I, conducted at Hospital de la Conception in France that demonstrated significant improvement in hand function, pain, and Raynaud’s severity in patients with scleroderma affecting the hands.1 Cytori supported this trial in the form of devices, consumables, and training. Cytori is co-sponsoring SCLERADEC II, a follow on multi-center, controlled study in France.


Osteoarthritis:

Cytori has initiated ACT-OA, a US IDE Phase IIA/B clinical trial of the ECCO-50 therapeutics in patients with osteoarthritis affecting the knees. A total of 90 patients will be enrolled in this randomized, double-blind, placebo controlled clinical trial. The study, which will begin enrollment early in 2015, will examine the safety and efficacy (symptom relief, function, and activity level) of ECCO-50 at multiple time points through 48 weeks. Data should be available in 2016.


Thermal Burn and Radiation Injury – BARDA Contract:

In August 2014, Cytori received formal notification that BARDA* executed a contract option to fund research, development, regulatory, clinical, and other tasks required for initiation of a pilot clinical trial of Cytori Cell Therapy in thermal burn injury for a total of approximately $12.1 million. In December 2014 BARDA added $2 million in supplementary funding to this option by contract modification. Upon IDE approval by the FDA, BARDA anticipates exercising Option 2 funding in order to cover costs associated with execution of a pilot clinical trial, currently estimated at approximately $8.3 million, bringing the combined value to up to $22.4 million. In addition to development and clinical activities in Options 1 and 2, BARDA may later choose to fund a thermal burn pivotal trial through the FDA approval submission process (Option 3), as well as to fund further development activities related to thermal burn compromised by concomitant radiation exposure (Option 4).


Urinary Incontinence:

Cytori has agreed to provide partial support to a planned Japanese investigator/government sponsored trial of Cytori Cell Therapy for male urinary incontinence following radical prostatectomy. This trial is based on a previously published2 feasibility trial conducted at Nagoya University in Japan. This trial demonstrated improvements in leakage, urethral closure, and patient quality-of-life assessment in men with urinary incontinence following radical prostatectomy for prostate cancer. The primary funding and support of the trial will come from the Japanese Ministry of Health, Labor and Welfare and Nagoya University. We will report when the protocol is finalized and the timetable for the trial is available. If efficacy is shown is this trial, the intention is to seek regulatory claims for this indication and reimbursement for the therapy.


Investigator Initiated Studies

By providing real-time access to Cytori Cell Therapy processing technology in markets where it has class I or CE Mark approval, the Celution® System has become an important research and development tool for physicians. This enables them to study the potential of our technology in Institutional Review Board (IRB) and Medical Ethics Committee (MEC)-approved studies. A number of investigator-led trials have been completed, are in process or are planned for a range of conditions, including the following:

  • Anterior cruciate ligament repair
  • Bone repair
  • Burn scar
  • Chronic wounds
  • Critical limb ischemia
  • Cryptoglandular fistulas
  • Meniscal Repair
  • Stress urinary incontinence
  • Scleroderma hand disease
  • Vocal cord repair

Investigator-led studies are important in that they generate additional data on the potential of Cytori Cell Therapy in conditions where there are distinct medical needs that are not within the current Cytori development plans. Based on early pilot data, Cytori will be able to choose the most promising applications for further development.


COMPLETED TRIALS


Chronic Heart Failure

The ATHENA I and II trials are multi-center, randomized, double-blind safety and feasibility trials to investigate the use of Cytori Cell Therapy in patients with heart failure due to ischemic heart disease. The trials were originally planned to enroll 45 patients each and examine two dosages of the therapeutic formulation OICH-D3.

The trials incorporate several endpoints, including peak oxygen consumption (VO2 max), perfusion defects, heart failure symptoms, health-related quality of life, left ventricle end-systolic and diastolic volume, and ejection fraction at six and 12 months. Enrollment was truncated at 31 patients in 2014 due to a prolonged trial delay in 2014; however, data will be available for review in 2015.

PRECISE is a 27 patient safety and feasibility study in Europe designed to evaluate the use of Cytori Cell Therapy in chronic ischemia patients on maximal medical therapy without other options for revascularization. Data from the PRECISE trial indicated the feasibility of obtaining and delivering Cytori Cell Therapy to patients with significant heart disease. The data provided early indications of efficacy that provided the rationale for the ATHENA trials in the US.


Acute Myocardial Infarction

The ADVANCE Trial is a randomized, placebo controlled, double-blind trial that enrolled 23 patients at four centers and was a confirmatory study to APOLLO (see below). The trial was approved for patients with ST-elevation myocardial infarction (STEMI) and allowed up to 35 centers, predominantly in Europe. The primary endpoint of the trial is reduction in infarct size as measured by cardiac magnetic resonance imaging (MRI). All available data are supportive of the current known safety profile for Cytori Cell Therapy.

The APOLLO Trial is a 14 patient study in Europe designed to assess the safety and feasibility of Cytori Cell Therapy in patients with ST-elevation myocardial infarction (STEMI). Enrollment and 36 month patient follow up is complete. The study demonstrated the feasibility of intracoronary injections of Cytori Cell Therapy in STEMI patients and provided the rationale for the ADVANCE trial.


Breast Cancer Reconstruction

The RESTORE-2 study is a Phase IV (post-market) European study that evaluated safety and efficacy of Cytori Cell Therapy for breast deformities post segmental breast resection (lumpectomy) with or without radiation therapy. This prospective, single-arm, open-label, multi-center study enrolled 71 patients with defects ranging from 25-150 mL at seven European clinical centers. The procedure was shown to be safe and well tolerated. The efficacy data demonstrated high degrees of patient (75%) and investigator (85%) satisfaction following cell enriched fat grafting to treat breast defects post-breast conservation therapy.

References:

1Granel, B, et al. Safety, tolerability and potential efficacy of injection of autologous adipose-derived stromal vascular fraction in the fingers of patients with systemic sclerosis: an open-label phase I trial. Ann Rheum Dis. 2014;0:1–8.
2Gotoh, M, et al. Regenerative treatment of male stress urinary incontinence by periurethral injection of autologous adipose-derived regenerative cells: 1-year outcomes in 11 patients. Intl Journal of Urology. 2013; 10.1111;1–7.

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December 10, 2014
FDA Grants Cytori Conditional Approval for a U.S. Pivotal Clinical Trial in Scleroderma