E-CEL UVEC Cell Therapy for Anal Fistulas

Overseen By Jordan Augsburger

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Weill Medical College of Cornell University

Must not be taking: Steroids, Investigational drugs

Disqualifiers: Abscess, Active infections, Renal impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: Up to 4 treatments

39 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using special cells from umbilical veins, known as E-CEL UVEC cell therapy, to heal simple anal fistulas. These are small tunnels that can form between the end of the bowel and the skin near the anus. The main goal is to determine if these cells are safe and if they improve healing when combined with other procedures. Participants may receive different treatments, such as injections alone or with additional surgical steps, to compare outcomes. This trial is suitable for adults with a simple anal fistula with two or fewer tracts and no history of Crohn's disease or ulcerative colitis. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on ongoing steroid treatment or have been treated with steroids in the last 4 weeks.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research is investigating the safety of using E-CEL UVEC cells, derived from the inner lining of blood vessels, to treat anal fistulas. As this treatment remains in the early stages, solid data on its safety is not yet available. Researchers are primarily focused on determining its safety for humans.

Due to its early phase, information on tolerance and potential side effects is limited. During this phase, scientists closely monitor how the treatment affects participants, watching for any issues. Current studies aim to assess the safety of E-CEL UVEC cells, but further research is necessary for confirmation.

For those considering joining this trial, the main goal is to determine if this new treatment can safely aid in healing anal fistulas. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

E-CEL UVEC is unique because it offers a novel cell therapy approach for treating anal fistulas, which are typically managed with surgery, like fistulotomy, or other methods such as setons or fibrin glue. This treatment uses viable E-CEL UVEC cells, which are injected directly into the fistula tract and its internal opening to promote healing from within. Researchers are excited about this therapy because it targets the problem at a cellular level, potentially enhancing tissue regeneration and reducing the need for more invasive surgical procedures. Additionally, the option for multiple treatments and varying doses provides flexibility in tailoring the therapy to individual patient needs, which could lead to better outcomes.

What evidence suggests that E-CEL UVEC cell therapy could be an effective treatment for anal fistulas?

Research has shown that stem cells from fat tissue may help treat complex perianal fistulas, which resemble anal fistulas. This trial will investigate the potential of E-CEL UVEC, which uses cells from the lining of blood vessels in human umbilical veins, to heal anal fistulas. Participants will receive E-CEL UVEC cell therapy through different treatment arms, each with specific procedures and dosing regimens. These cells may assist in repairing damaged tissue and promoting healing. Although few direct studies exist on E-CEL UVEC for anal fistulas, the method builds on other successful treatments. Early results appear promising, but further research is needed to confirm its effectiveness. ^{2 3 4 6 7}

Who Is on the Research Team?

Jeffrey W Milsom, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

Adults with simple anal fistulas, not exceeding 2 tracts or 3 inches in length, without Crohn's disease/Ulcerative Colitis. Participants must be able to consent and agree to a fistulotomy surgery. They should not have certain health conditions like severe renal or hepatic impairment, active infections, or recent major surgeries. Contraception use is required for those who can conceive.

Inclusion Criteria

Maximum tract length of 3 inches

Subject must be willing to use a highly effective method of contraception from the start of the screening period throughout the study period

For female subjects of childbearing potential: A negative serum or urine pregnancy test at screening is required prior to enrollment

Exclusion Criteria

I do not have setons or they will be removed before treatment.

My kidney function is reduced, with creatinine clearance below 90 mL/min or serum creatinine ≥ 1.5 times the normal upper limit.

I have an immune system condition, such as HIV or AIDS.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive E-CEL UVEC cell therapy in conjunction with fistulotomy or curettage for anal fistula treatment

Up to 4 treatments

1-4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of healing and adverse events

24 weeks

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• E-CEL UVEC

Trial Overview The trial tests if endothelial cells from human umbilical veins (E-CEL UVEC) are safe when used alongside standard surgical treatment (fistulotomy) for healing simple anal fistulas.

How Is the Trial Designed?

Group I: Cell Therapy Treatment Part BS2 Experimental Treatment 1 Intervention

Subjects in Part B2-S will have the same eligibility criteria and would undergo the same procedure as described in Part B1, except that B2-S subjects will also have suturing and injection of the internal opening.

Group II: Cell Therapy Treatment Part BS1 Experimental Treatment 1 Intervention

Adult subjects with simple perianal fistula who meet all eligibility criteria to participate in Part B of the study will be treated in the outpatient setting with curettage and E-CEL UVEC cells without fistulotomy. E-CEL UVEC cells will be injected along the two sides (180 degrees apart from each other) of the whole length of the curetted anal fistula tract.

Group III: Cell Therapy Treatment Part BM2 Experimental Treatment 1 Intervention

This cohort comprises of multiple (M) treatments with E-CEL UVEC injections. The difference between Part BM1 and Part BM2, is that the subjects in the latter cohort receive double the dose of E-CEL UVEC cells per treatment. Subjects in Part BM2 will have the same eligibility criteria as Part BS1, BS2 and BM1 cohorts and would undergo the same treatment procedure as described in Parts BS1, BS2 and BM1. Every treatment consists of the percutaneous injection along both sides of the fistula tract plus injection of the internal opening via direct anoscopic visualization (described in the next paragraph). Dosing is 30 x 106 viable E-CEL UVEC cells into the area of the internal opening and minimum 30 x 106 viable E-CEL UVEC cells per centimeter along the fistula tract (15x106 viable E-CEL UVEC cells, each side per centimeter of the tract). All subjects in this cohort receive up to 6 treatments over 6 months. The six treatments are administered on visits WK 0, 3. 6, 9, 12 and 24.

Group IV: Cell Therapy Treatment Part BM1 Experimental Treatment 1 Intervention

Subjects in Part BM1 will have the same eligibility criteria and would undergo the same procedure as described in Part B1, except that B2-M subjects in this cohort are eligible for up to 4 treatments (versus 1 in Part BS2).

Group V: Cell Therapy Treatment Experimental Treatment 1 Intervention

Patients who present with simple anal fistula and elect to undergo fistulotomy for treatment will be eligible to have E-CEL UVEC injected into the fistula at the time of fistulotomy to aid in healing.

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Angiocrine Bioscience

Industry Sponsor

Trials

6

Recruited

250+

Published Research Related to This Trial

The use of adult stem cells (ASCs) combined with fibrin glue for treating perianal fistulas demonstrated a strong safety profile, with only two unrelated adverse events reported among 34 patients over a follow-up period averaging 38 to 42 months.

However, only 7 out of 12 patients treated with ASCs plus fibrin glue remained free of fistula recurrence after more than 3 years, indicating that while the treatment is safe, its long-term efficacy in preventing recurrences may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of patients undergoing adipose-derived adult stem cell administration to treat complex perianal fistulas. Guadalajara, H., Herreros, D., De-La-Quintana, P., et al.[2022]

Teduglutide treatment for enterocutaneous fistula (ECF) was found to be feasible and well-tolerated, with 5 out of 6 subjects showing a significant decrease in fistula drainage during the treatment period, which was not observed during standard-of-care alone.

One subject experienced complete closure of the fistula while on teduglutide, indicating its potential efficacy, although the study was limited by small sample size and early termination due to slow enrollment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teduglutide for the treatment of low-output enterocutaneous fistula - A pilot randomized controlled study. Yeh, DD., Vasileiou, G., Abdul Jawad, K., et al.[2022]

In a study of 8 patients with complex fistulas, all 4 enterocutaneous fistulas (ECFs) treated with vacuum-assisted closure (VAC) therapy closed spontaneously, demonstrating its efficacy in managing this challenging condition.

VAC therapy not only promotes skin healing but also aids in the management of enteroatmospheric fistulas (EAFs), with 3 out of 4 EAFs transitioning to ECFs and one closing spontaneously, suggesting its versatility in treating different types of fistulas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vacuum Assisted Closure (VAC) therapyTM as a swiss knife multi-tool for enteric fistula closure: tips and tricks: a pilot study. Pepe, G., Magalini, S., Callari, C., et al.[2022]

In a study of 135 patients who underwent surgery for enterocutaneous fistulae (ECF), the overall mortality rate was 8%, while 84% of patients survived with a closed fistula, indicating that surgical repair can be effective.

The main factor predicting mortality was ECF recurrence, with significant risk factors for recurrence including inflammatory bowel disease, a diagnosis-to-surgery interval of 36 weeks or longer, and the location of the fistula in the small intestine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors for recurrence after repair of enterocutaneous fistula. Brenner, M., Clayton, JL., Tillou, A., et al.[2014]

Mesenchymal stromal cells (MSCs) from adipose tissue can effectively adhere to suture filaments, promoting better healing of enterocutaneous fistulas (EF) in a rat model, as confirmed by microscopy techniques.

In a study involving 22 Wistar rats, the group treated with suture filaments attached to MSCs showed a significantly greater reduction in fistula size (90.34%) compared to those receiving MSC injections (71.80%) or no treatment (46.54%), suggesting that this method could be a promising new approach for EF treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cells from adipose tissue attached to suture material enhance the closure of enterocutaneous fistulas in a rat model. Volpe, BB., Santos Duarte, Ada S., Ribeiro, TB., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04190862

E-CEL UVEC as an Adjunct Cell Therapy for Treatment ... The purpose of this study is to test the safety of E-CEL UVEC® cells and see what effects (good and bad) it has on your anal fistula. It is hoped, that the E- ...

2. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/239450

E-CEL UVEC as an Adjunct Cell Therapy for Treatment of ... The purpose of this study is to determine if endothelial cells derived from human umbilical vein are safe for use in conjunction with ...

3. withpower.com withpower.com/trial/phase-1-rectal-fistula-2020-49d75

E-CEL UVEC Cell Therapy for Anal Fistulas Research shows that using stem cells from fat tissue has been promising in treating complex perianal fistulas, which are similar to anal fistulas. This suggests ...

4. jcto.weill.cornell.edu jcto.weill.cornell.edu/open_clinical_trials/an-open-label-single-center-investigator-initiated-phase-1b-trial-of-e-cel-uvec-as-an-adjunct-cell-therapy-for-treatment-of-anal-fistulas

An Open-Label, Single-Center, Investigator Initiated Phase ... The goal of the study is to evaluate the preliminary safety of human umbilical vein cells in anal fistula healing. Participants will receive injections of the ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06456073

NCT06456073 | E-CEL UVEC Treatment for Anal Fissures The study is being conducted to determine if E-CEL UVEC cell injections will be safe and would have any effects on healing of the anal fissure. Detailed ...

6. trialx.com trialx.com/clinical-trials/listings/241552/e-cel-uvec-as-an-adjunct-cell-therapy-for-treatment-of-anal-fistulas/

E-CEL UVEC as an Adjunct Cell Therapy for Treatment ... The purpose of this study is to test the safety of E-CEL UVEC® cells and see what effects (good and bad) it has on your anal fistula. It is ...

7. datamed.org datamed.org/dataset/c8d8fedd-d2d9-4788-8dbf-f448f935c8c2

Metadata - DataMed Data Discovery Index E-CEL UVEC as an Adjunct Cell Therapy for Treatment of Anal Fistulas ... cells anal study endothelial human umbilical vein fistulas cell safe use line. This ...