Cook MyoSite AMDC Fecal Incontinence Clinical Study 09-025

• Research type

  Research Study

• Full title

  A Prospective Nonrandomized Study of Autologous Muscle Derived cell (AMDC) Transplantation for Treatment of Fecal Incontinence

• IRAS ID

  141522

• Contact name

  Charles Knowles

• Contact email

  c.h.knowles@qmul.ac.uk

• Sponsor organisation

  Cook Myosite, Incorporated

• Eudract number

  2013-004672-35

• Clinicaltrials.gov Identifier

  NCT01600755

• Research summary

  Summary of Research
  This purpose of this study is to to test the safety and feasibility of Autologous Muscle Derived Cells (AMDC) as a treatment for fecal incontinence in men and women. AMDC therapy seeks to allow remodeling of the anal sphincter in patients with fecal incontinence from either defined structural defects to or a generalized weakening of the anal sphincter. This treatment is hypothesized to reduce symptoms of fecal incontinence and improve patient quality of life by strengthening the anal sphincter muscle. The procedure uses Cook MyoSite Incorporated AMDC. AMDC are muscle progenitor cells isolated from a patient’s skeletal muscle. The tissue is collected from a muscle biopsy collected from the patient’s thigh and sent to the manufacturer for processing. The resulting cells are sent back to the physician who injects the cells into the patient’s anal sphincter in an outpatient procedure using a small needle under direct vision. Endoanal ultrasound may be used at the physician’s discretion to visualize the location of the injection needle within the anal sphincter. The study is a prospective nonrandomized study and will treat a total of 30 patients. The primary objective is to determine the incidence of product- or procedure-related adverse events associated with the use of AMDC. The secondary outcome objectives are to study the effect of AMDC treatment for fecal incontinence. Patients will be followed for 12 months.

  Summary of Results
  When a new drug or therapy is being developed it needs to be studied to understand how it works and to determine whether this drug or therapy is safe and effective to treat the condition for which has been developed. It takes a lot of people and many studies around the world to advance medical science. This summary only shows the results from this one study and other studies may find different results.

  1.1. Study name
  • Study of Muscle Cell Injection for the Treatment of Fecal Incontinence
  • A prospective Non-randomized Study of Autologous Muscle Derived Cell (AMDC) Transplantation for Treatment of Fecal Incontinence

  1.2. Protocol number
  • 09-025/GIFI

  1.3. EU Trial number
  • EudraCT Number: 2013-004672-35

  1.4. Other identifiers
  • ClinicalTrials.gov: NCT01600755

  1.5. Abstract
  The purpose of this clinical study was to see if the injection of iltamiocel, a new experimental treatment for fecal incontinence, is safe and effective. This study tested a product called iltamiocel which is a preparation of muscle cells originating from the patient’s body. The study involved 48 patients (45 women and 3 men) with an average age of 61 years who had accidental fecal leakages. The study was performed in two countries (Canada and United Kingdom). The results from the study showed that some patients reported a reduction in the number of accidental fecal leakage at the end of the study. In addition, this study found that injection of iltamiocel is safe with no serious unwanted side effects.

  2. Who sponsored the study?
  This study was financially supported by Cook Myosite Inc, a U.S based biotechnology company focusing on regenerative medicine.

  Contact information:
  Cook MyoSite,
  105 Delta Drive
  Pittsburgh, PA 15238, USA.
  Phone: 412.963.7380
  Fax: 412.967.9729

  3. General information about the clinical trial
  3.1. This study took place in Canada and the United Kingdom.

  3.2. This study started in March 2013 and ended in October 2021. After enrollment patients were followed for 12 months.

  3.3. This was a Phase 1/2 study. In a Phase 1/2 study, a new treatment is tested on a small number of patients to understand how the medicinal product works and if there are any unwanted side effects associated with its use. In this study, researchers injected the iltamiocel cellular product in the muscle of the anal sphincter of patients with accidental fecal leaks (fecal incontinence) to find out if iltamiocel is safe for the patient. The study also tested if the product could improve the symptoms of fecal incontinence by reducing the number of accidental leakage recorded by the patient during a period of 28-day fecal incontinence diary. The effect of the treatment on the quality of life of the patients was also investigated using a questionnaire.

  4. What patients/people were included in this study?
  4.1 Number of subjects included in the trial This study included 48 patients with fecal incontinence. All patients that participated in this study had tried other treatments for fecal incontinence prior to initiating this study.
  The study was run in Canada and the United Kingdom. In Canada, 33 patients were enrolled and in the United Kingdom, 15 patients were enrolled.

  4.2. Age group and gender breakdown
  Of the 48 patients that participated in this study, 45 were female and 3 were male. Twenty-four patients (50%) were between 18 and 64 years old, 23 (47.9%) were between 65 and 84 years old and one patient (2.1%) was 85 years old.

  4.3. Inclusion and exclusion criteria
  • Patients enrolled in this study were at least 18 years old and had frequent accidental leakage of feces (fecal incontinence) due to a weakened or damaged anal sphincter (the muscle around the anus).

  • Patients had to have tried other treatments for fecal incontinence for at least one month before enrolling in this study and had failed to see improvements in their symptoms. These treatments included modification of their diet, medications for diarrhea, and exercise programs aimed to reinforce the muscle of the pelvis.

  • Patients that had conditions that affected the nerves that send electrical signals to the muscle (neuromuscular disorders) could not participate in this study.

  • Patients that had their anal sphincter replaced with an artificial one or had surgery in which the anus or the rectum was damaged or removed could not participate in this study.

  • Patients with chronic inflammation of the digestive tract which can cause severe diarrhea like Crohn’s disease or ulcerative colitis could not participate in this study.

  5. Which medicines were studied?
  The treatment investigated in this study is called iltamiocel. Iltamiocel is a research product consisting of Autologous Muscle Derived Cells (AMDC) which is a preparation of muscle cells originating from the patient’s own body. To make iltamiocel, a sample of muscle cells is taken from the patient’s thigh using a typical biopsy procedure. These cells are then grown in a laboratory to produce the research product. This product is then injected into the muscle tissue of the anal sphincter. In this study, approximately 250 million cells were injected into the anal sphincter of the patient. It is believed that these cells will become part of the tissue where they have been injected and it is hoped that the cells will strengthen the anal sphincter and thereby help prevent future leakage.

  6. What were the side effects?
  Side effects are unwanted medical events that happen during the study and are reported because the doctor conducting the study (investigator) believes the side effects were related to the treatment. Not all patients in this study had side effects.

  None of the patients participating in this study reported serious side effects. Serious side effects are reactions to the treatment that are life-threatening or require the patient to have to go to the hospital.

  One patient (2.1%) reported a side effect consisting of inflammation of the area where the experimental product was injected (injection site inflammation) which was believed to be caused by the iltamiocel product.

  Five patients (10.4%) reported side effects that were believed to be caused by the injection procedure itself. Each of the five subjects reported one of the following side effects: discoloration of the area where the product was injected (injection site discoloration), inflammation of the injected area (injection site inflammation), pain at the injected area (injection site pain), dizziness and pain due to the injection procedure (procedural pain).

  Twenty patients (37.7%) reported a total of 27 side effects that were believed to be caused by the biopsy procedure. The two most frequent side effects related to the biopsy procedure were pain (procedural pain) which was reported by 13 patients (19.7%), and bruising in the area where the tissue sample was obtained (procedural contusion) which was reported by 5 patients (7.6%).

  7. What were the overall results of the study?
  The study was completed as planned. Of the 48 patients who started the study only one (2.1%) withdrew from the study before completing the last visit (12 months visit).
  In this study, it was found that 12 months after the injection of the iltamiocel experimental product, some patients reported fewer fecal leakages during the 28-day diary compared to the leakage they reported at the beginning of the study. This does not mean that everyone that participated in this study had these results.

  The following are the main results of this study:
  • After 12 months after the start of the study, patients reported in median a lower number of fecal leakages compared to the number of leakages they had at the beginning of the study during the 28-day diary (7 leakages vs 16 leakages). This does not mean that all patients had a decrease in leakages at the end of the study.

  • Similarly, after 12 months, patients reported in median a lower number of days with fecal leakages during the 28-day diary compared to the beginning of the study (5 days vs 12 days). As for the number of leakages, this does not mean that all patients had a reduction in the number of days with leakages.

  • When the response to the treatment was defined as at least 50% reduction in the number of fecal leakages at 12 months compared with before the treatment, 22 out 48 (45.8%) patients injected with the iltamiocel experimental product met such definition. When the response was defined as at least 75% reduction in the number of leakages at 12 months compared with before the treatment, 10 out 48 (33.3%) patients met such definition. At the end of the study, 10 patients (20.8%) reported zero leakage during the 28-day diary period.

  • During this study, patients were asked 5 questions as part of a questionnaire called Cleveland Clinic Incontinence Score (CCIS). CCIS assesses the frequency and type of incontinence episodes (solid, liquid, gas, wears pad, lifestyle alterations). In this questionnaire, the frequency with which each type of incontinence occurs is rated on a scale from 0 (never) to 4 (always or to 1/day). The sum of the frequencies is added to yield a total score that can range from 0 to 20, with higher scores indicating higher levels of incontinence. Twelve months after receiving iltamiocel injection, patients reported on average a 2.9 points reduction of CCIS score which represents a general improvement of incontinence symptoms compared with before the treatment.
  
  • To evaluate the impact of the treatment on the quality of life, patients were asked to fill out the Fecal Incontinence Quality of Life questionnaire (FIQL). The questionnaire consisted of 29 questions pertaining to different aspects of the patient’s quality of life and which form four scales: lifestyle, coping/behavior, depression/self-perception, and embarrassment. Each scale is scored from 0 to 4, with a higher score representing a better quality of life. Twelve months after receiving iltamiocel injection, patients reported an increased score for all four scales compared with the beginning of the study. The average increase for the lifestyle scale was +0.6 points, for the coping/behavior scale was +0.5 points, for the depression/self-perception was +0.4 points, and for the embarrassment scale was +0.6 point. Overall, based on the FIQL questionnaire, patients reported an improvement in quality of life compared with the beginning of the study however this does not mean that all patients had the same level of improvement.

  8. How has this study helped patients and researchers?
  This was the first study that investigated the use of the iltamiocel experimental cellular therapy for the treatment of patients with fecal incontinence.

  The main objective of this study was to evaluate if the iltamiocel treatment is safe. The iltamiocel experimental product, the biopsy procedure, and the injection procedures were all safe with no severe side effects reported. However, due to the limited number of patients participating in this study, it is not possible to rule out the possibility that severe side effects may occur when many more patients are treated with this product, although this is unlikely.

  Since this was the first study in which this new treatment was tested in patients with fecal incontinence, patients with different characteristics including age, sex, the severity of the condition (number of fecal leakages), cause of the fecal incontinence (obstetric injury or other cause), and duration of the condition have all been included in the study. This diverse population of patients may in part explain why some patients had a better response compared to others.

  Findings from this study will be therefore used to inform the researchers on how to design the next studies and how to define which patients with fecal incontinence may benefit the most from this new cellular treatment.

  9. Are there plans for other studies?
  Further clinical trials with the iltamiocel cellular therapy are planned. In the next study, iltamiocel will be tested in a larger number of patients with fecal incontinence and the researchers will compare the iltamiocel experimental product with a placebo (identical-looking product but with no cells).

  10. Where can I find more information about this study?
  To learn more about this study, you can find more detailed information on this website:
  https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agba4yu73OCS9U-2BkKS40W1kfatiYvtk1-2B2gi1K6vKImual9G6VG4-2FeFhNKGHEnJKTVSoK0vvfBrn1LTIPSnlRmIT9S9nLmzX1XYQx-2FhON4WvFYStzuHwbAd3iiHr9N33lWoA-3D-3Dbfhg_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YIYQfeMRLcXhxJAjALSvJ6MBPxpXfKJzG3WJ1TidGG-2BMmf-2B0EqlL1-2FHK9wP-2FG3NZ97jxuePUPiRPDNax5Tnq00-2FhfgTOe9fKQ-2BBWvVAT8ju5tvQz3Mm9GD4F4pGKL7Q7TFtgOd9fFfky0yQVqn0AFgbUHCIx87sEzFPSMrWwjKbzA-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C286a3e92f6df4b570da608db037aad93%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638107597650538598%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=cKSdhnZ1emNkYOfs9FDF4t5znzHVBOdgDDHOY8FbRXE%3D&reserved=0

• REC name

  London - Brighton & Sussex Research Ethics Committee

• REC reference

  14/LO/0438

• Date of REC Opinion

  25 Apr 2014

• REC opinion

  Further Information Favourable Opinion