Gerard J. Criner, MD, FACP, FACCP, outlines the details of the Gala Therapeutics RheSolve Study for treating patients with chronic bronchitis.
below. Like to describe to you the gallo therapeutics resolve study which is an important study for treating patients with chronic bronchitis. My name's drawer Criner and that professor and charity department of forensic medicine and surgery at Temple University. These are my disclosures. As one of the disclosures. I am a funded investigator for one of the resolve trials. So the intention of this study is to treat patients with chronic bronchitis. It's estimated that about 60% of patients with COPD suffer from chronic bronchitis and chronic bronchitis as you know, is characterized by persistent excessive mucus production and a cough. And the importance of chronic bronchitis is that it can contribute heavily to the frequency and severity of exacerbations which can market markedly in pay our patient's quality of life. They can contribute to patients mortality. Despite this, the importance of chronic bronchitis. There's no currently accepted therapy that targets the path of physiology and mucus hyper secretion nor effectively medically treats it well. The gallery ox study is intended to treat that by using the redox catheter in patients with chronic bronchitis. And in this study a non thermal pulse electric field is used to blake the airway epithelium to decrease goblet cell hyperplasia and function and to improve patient symptoms. And this procedure is called bronchi oh rio plasticity. There's a little video that shows um in detail how the procedure is done. The patient is provided with general anesthesia under regular fashion through the endotracheal tube, flexible fiber optic bronchoscopes is placed and the airways are treated from the segmental and sub segmental regions on one lung at a time over two visits during this period of time, the catheter is placed into the targeted portion of the airway and as you'll see a basket is inflated to adhere to the airway wall. About five seconds of pulse electrical activity is applied to oblate the airway epithelium and uh specifically targeting gobbled cells and limiting their ability to create mucus hyper secretion. The other portions of the airway wall preserved such as the structures below the sub mucosa. So the integrity of the airway wall function is maintained over a period of time. Repopulation airway wall with more appearing more normal appearing airway epithelium can occur. And hopefully this restores more normal airway function. So the redox chronic bronchitis clinical program has had several components to it. Uh Several of these studies have been completed. The out of the US first in human studies, which was a first a man uh 30 patients study done in Austria Chile in Australia has been published and I'll describe some of the detail to you. A Canadian first in human study was done in 10 subjects and it's been completed and its data is currently being analyzed And ongoing is a European registry which is a open label study, including up to 100 subjects of 10 sites with two years. Follow up. So at this point more than 85 patients have been treated worldwide. That shows consistent data in these first inhuman and this European registry of showing a favorable safety profile profile and also indicators of patient benefit In the US there's been two studies in early feasibility study which was a single cohort, 21 patients study and 10 centers with five year follow up that has been completed And has been uh process of being published and then a pivotal trial is currently ongoing. And this will be the study that will be submitted for FDA approval. This is a 2-1 trial blinded study, both for the patient as well as the uh the procedural lists. It will have a controlled parallel group. It will be up to 270 patients that have been enrolled, followed for up to two years at 40 sites throughout the us Canada and some European centers. This is some of the data for the first in human studies, 30 patient European uh and uh study that was published in Austria Chile and Australia. And this was the patient population that made up this group 67 years of age, more males than females. B. M. I. was 27. The smoking histories about 40 pack years. But the as you can see the severity of airflow obstruction was really the mean level was at a moderate category. And most of these patients, 70% of them had gold stages zero through two for which only 30% of the patients had severe airflow obstruction stage three. As a result of that, few of the patients had emphysema. The minority 9%. These patients tended to be hyper inflated not only because of the presence in the minority of emphysema, but also of airway while thickening. That lead to increased airways resistance in gas traffic. And despite this more moderate level of airflow obstruction, these patients were highly symptomatic. As you can see. Cat and sTR Q scores were very elevated, signifying a significantly symptomatic patient group and as you can see the outline of therapies that are shown down below the percentage of the patients that were on inhaled bronchodilators, steroids or use of reflective glass. These are the outcome of the study of the major out comes were changing sTR. Q. And the cat score. And as you can see with the minimal important clinical difference of a four point reduction in the ST George respiratory questionnaire. The patients in this study at 36 and 12 months exceeded the minimum important clinical difference By at least 3-4fold throughout the study phase. And in terms of the cat score that also improved with a minimal important clinical difference of two patients. They again 36 and 12 months basically had 3 to 4 fold the improvement in the cat score similar to what they experience with the change in str Kiev. Looking at these patients changes in the cat score that I just reported to you over all. These patients had a decrease in cough chest tightness as well as sputum production but they also had an improvement in their sleep quality and tended to be less breathless and more likely to have more social engagement in a higher reported energy level. And although this study was small pilot, 30 patients following for one year which was seen was a decrease in the incidence or prevalence of moderate as well severe exacerbations when patients were followed up for a period of time. So signal that perhaps this treatment may be favorable and improving only patient symptoms but resulting in a decrease in the frequency and the severity of exacerbations. Here's some of the history pathology results that were shown in the study looking at goblet cell hyperplasia. And as you can see in this pre treatment patient who had a significant amount of Goblet cells that are present Large in size. There's about 39% reduction. Uh three months in patients being gobbled score in 54 lungs that were examined from these investigators. And it's also correlated with an improvement in air flow as measured by examination of dynamic cT scans that were performed at baseline in the three months after treatment. And as you can see here shown to the right there's about a 20% increase in distal airway volume by H. R. C. T. In patients following treatment. So what was the safety profile was pretty uh pretty substantial. There was only four adverse events and seen in three patients. Uh One of the patients had to adverse events exacerbations made up half of them. Uh Most of these are in a recovery period of time, pneumonia, mucosal scarring with general anesthesia and exacerbation was later phase in one of the subjects. So this has led to resolve study which is a prospective randomized double shot sham controlled parallel group study of treatment phase 2 to 1 of Rio's procedures. Energy delivery versus the shamrocks procedure without energy delivery. Again, 270 patients 2 to 1 treatment that control 40 sites in the US and outside U. S. Centers. These are the key eligibility criteria cigarette smoking of at least 10 pack years. Stop smoking in the last six months significant cough and mucus hyper secretion. Is president caused by chronic bronchitis. Gold stages 123 similar to the other studies that I told you about with an F. E. V. One greater than 30% of predicted severe emphysema is excluded. And because of this pulse electrical activity that's provided pacemakers and patients with I. C. D. S are excluded. So if you have any questions about this study or any patients that you like to refer to us, this is our contact information that you can either contact us by email or by phone. Thanks very much for your attention and I hope to see if we can help any of your patients