A Phase IB/IIA Study of ExoFlo, an Ex Vivo Culture-expanded Adult Allogeneic Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicle Isolate Product, for the Treatment of Perianal Fistulizing Crohn’s Disease
Published: 09/06/2023
General Information:
To evaluate the safety and effectiveness of ExoFlo in patients with perianal fistula(s) due to Crohn’s disease.
Eligibility:
Inclusion Criteria:
- Adults 18-75 years old with Crohn's disease for at least 6 months
- Single or multiple perianal fistula(s)
- Patients must have failed at least one medical therapy within the last year (antibiotics, 6-MP, methotrexate, azathioprine, infliximab, adalimumab, certolizumab, ustekinumab, golimumab, vedolizumab, or small molecule inhibitors
- Patients must have failed surgery, including seton placement at least 2 weeks before the trial, or are not a surgical candidate or do not want to have surgery for the fistula(s)
- The medications used for Crohn's disease must have kept the disease stable for at least 2 months before receiving the study treatment (changes in dose of the medication or how often the medications is received is permitted)
- Patient must be willing to follow the study protocol
- Patient must be competent and able to provide written consent
Exclusion Criteria:
Any patient who meets any of the following will be unable to participate in this study:
- Heart, liver, kidney, or other diseases which may make it unsafe to participate in the study
- Presence of perianal abscess or infection, severe proctitis, ileal anal pouch, proctectomy, or rectovaginal fistula
- Significant changes in health status within six months before receiving the study drug would make it unsafe to receive the treatment
- Women who are pregnant or breastfeeding or trying to become pregnant
Study Details:
Study description/explanation of participation:
Patients who have perianal fistula(s) due to Crohn’s disease and have failed medications and surgery (or are unable to have surgery or not interested in surgery) with be treated with the study drug, ExoFlo, or a placebo (normal saline) via injection in the fistula site. If there is not healing within 3 months for the patients receiving a higher dose of the study drug or the placebo, a second dose will be given of the higher dose. Patients will be followed for a period of 12 months.
Description of treatment or intervention (mechanism of action):
The study drug, ExoFlo, decreases inflammation and promotes wound healing. ExoFlo may heal the fistula tract and reduce or prevent the need for additional surgeries, decrease symptoms, and improve quality of life.
Participation requirements:
Patients with perianal fistula(s) due to Crohn’s disease will be screened to make sure they meet the qualifications for the trial. The screening will include medical history, physical examination, vital signs, height and weight, electrocardiogram (ECG), and MRI if not done within 90 days of the trial, and blood work. If they are appropriate for the trial, patients will give their consent to participate. Patients will receive 1-2 doses of the study drug (ExoFlo), or the placebo (Normal Saline) by injection into the fistula. A total of 15 mL or 30 mL of the study drug or placebo will be given.
The day of the ExoFlo or normal saline injection procedure, the patient will then be given anesthesia so that the rectum and the fistula can be examined by the physician. A needle will then be used for injection of the study drug or normal saline. Patients will be watched closely following the injection the post-procedure area. Patients will return for physician visits the day after the procedure then the week following the procedure, then 6 weeks after the procedure, and 3 months, 6 months, and 12 months after the procedure. Tests will include general health assessment and blood work during weeks 2 & 6, and months 3, 6, and 12. For those patients receiving the higher dose of the study drug or normal saline, if the fistula is not healed and they have had no significant changes in condition during the trial, they will receive a second dose of the study drug and will have additional physician visits 1 day, 1 week, and 6 weeks after the treatment. General health assessments, physical examinations, and blood work will be done with each visit. The patient will be asked to complete questionnaires during each visit to evaluate symptoms associated with Crohn’s disease.
Possible risks and side effects:
There are no known risks of the IP on safety and efficacy as it has not been tested in perianal Crohn’s fistulas before. This does not mean that the investigational product has been proven to be a safe treatment for perianal fistulizing Crohn’s disease. One purpose of the current study is to assess the safety of the investigational product as a subcutaneous treatment for perianal fistulizing Crohn’s.
Theoretical or possible risks of the IP include injection site reactions in addition to other adverse reactions such as skin rash, swelling, blood in the urine, and/or significant changes in vital signs and heart rhythm. There may be side effects that the researchers do not expect or do not know about, which could be serious and/or life threatening. Tell your study doctor immediately about any new or unusual symptoms that you notice. The treatment of the side effects will depend on the symptoms.
Additional Risks Associated with Procedures:
Blood Samples: Blood sampling is taken by single needle-sticks or by a tube that is left in your arm. It has minimal risks which include bruising, dizziness, or pain. There may be side effects of having blood drawn such as:
- Fainting
- Redness
- Pain
- Bruising
- Bleeding
- Infection
- Blood clots, which may cause inflammation, swelling and pain
MRI: The patient will undergo a diagnostic imaging procedure known as magnetic resonance imaging (MRI) which uses a magnetic field and radio waves to create an image of internal body structures, to obtain additional information that may aid in diagnosing and treating your medical condition. Studies have shown that getting a lot of radiation at one time or getting many small doses over time may cause cancer. The risk of getting cancer from the one small radiation dose in this study is small.
Examination of Rectum Under Anesthesia: It usually involves a rigid sigmoidoscopy and/or proctoscopy and examination of the back passage while you are pain free and under a regional (spinal) or general anesthetic. After the procedure the patient will be taken to the recovery room. This is normally performed as a day case procedure but sometimes you may need to spend a night in hospital. The risks include complications common to all surgical procedures such as infection, bleeding, blood clots, heart problems, pneumonia, urinary retention, development of hernia and anesthetic risks.