E-CEL UVEC Cell Therapy for Anal Fistulas

Overseen By Ananya Sen

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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine if endothelial cells derived from human umbilical vein are safe for use in conjunction with fistulotomy for the treatment of simple anal fistulas. Endothelial cells are a special kind of cell in the body that line the inside surface of blood vessels. The goal of the study is to evaluate the preliminary safety of human umbilical vein cells in anal fistula healing.

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.

What data supports the effectiveness of the treatment E-CEL UVEC, AB-207 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 that E-CEL UVEC, which may involve similar cell therapy, could be effective for anal fistulas. ^{1 2 3 4 5}

Research Team

Jeffrey W Milsom, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. England 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. [2018]

2. Italy 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. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Long-term follow-up of patients undergoing adipose-derived adult stem cell administration to treat complex perianal fistulas. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Risk factors for recurrence after repair of enterocutaneous fistula. [2014]

5. England pubmed.ncbi.nlm.nih.gov

Teduglutide for the treatment of low-output enterocutaneous fistula - A pilot randomized controlled study. [2022]