Iltamiocel for Bowel Incontinence

(DigniFI Trial)

Recruiting at27 trial locations

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Cook MyoSite

Disqualifiers: Pregnancy, Cancer, Inflammatory bowel disease, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests if injecting muscle cells can help women who have chronic fecal incontinence due to childbirth injuries. The goal is to see if these injections can repair and strengthen their anal muscles, reducing incontinence episodes. Previous studies have shown that injecting muscle cells into the anal muscles can significantly improve fecal incontinence, particularly in patients with childbirth-related injuries.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, since participants must have failed conservative treatments like antidiarrheal medications for at least 6 months, it seems you may continue with those treatments.

What data supports the effectiveness of the treatment Iltamiocel for bowel incontinence?

Research shows that injecting muscle-derived cells, like those in Iltamiocel, has helped improve bowel control in people with fecal incontinence. Similar treatments have also shown promise in improving muscle function in urinary incontinence, suggesting potential benefits for bowel issues too. ^{1 2 3 4 5}

Is Iltamiocel safe for humans?

Research on Iltamiocel, also known as autologous muscle-derived cells, shows it is generally safe for humans. Studies for different conditions, like urinary incontinence and underactive bladder, reported no serious side effects. ^{1 2 6 7 8}

How is the treatment Iltamiocel different from other treatments for bowel incontinence?

Iltamiocel is unique because it uses autologous muscle-derived cells (cells taken from the patient's own muscle) to help repair and strengthen the muscles involved in bowel control. This approach is different from other treatments as it focuses on regenerating muscle tissue rather than just managing symptoms. ^{1 2 3 4 6}

Research Team

Ron Jankowski, PhD

Principal Investigator

Cook Myosite, Inc.

Eligibility Criteria

This trial is for adult women over 18 with chronic fecal incontinence due to childbirth injuries. They must have tried other treatments like diet changes or pelvic exercises for at least 6 months without success and score ≥9 on a specific incontinence scale.

Inclusion Criteria

I have tried treatments like diet changes and medications for my condition for over 6 months without success.

You have had a serious tear during childbirth.

You have a Cleveland Clinic Florida Incontinence Score (CCFIS) of 9 or higher at the beginning of the study.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single injection of iltamiocel or placebo

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants who received placebo may opt to receive an injection with their cells

Not specified

Treatment Details

Interventions

• Iltamiocel (Cell Therapy)
• Placebo (Other)

Trial Overview The study tests the effectiveness of a single injection of Iltamiocel (a cell therapy) versus a placebo in reducing episodes of bowel leakage. Participants are randomly divided into two groups, one receiving Iltamiocel and the other a placebo.

Participant Groups

Group I: Iltamiocel Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Cook MyoSite

Lead Sponsor

Trials

14

Recruited

1,100+

Findings from Research

Iltamiocel, a cellular therapy using autologous muscle-derived cells, was found to be safe with no serious adverse events reported in a study of 48 adults with fecal incontinence.

At 12 months post-treatment, participants experienced a significant reduction in fecal incontinence episodes and improved quality of life, with over half of the participants showing a ≥50% reduction in episodes and nearly a quarter achieving complete continence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Iltamiocel Cellular Therapy for the Treatment of Fecal Incontinence. Results of a Phase 1/2 Study. Knowles, CH., Canestrari, E., Jankowski, RJ., et al.[2023]

In a phase I clinical trial involving 10 patients with intrinsic sphincter deficiency (ISD), periurethral implantation of myofibres containing muscle precursor cells (MPCs) significantly increased intraurethral pressure and improved continence, with four out of five women experiencing notable improvements over 12 months.

The procedure was found to be safe, with no serious side effects reported, indicating that myofibre implantation could be a promising one-step treatment for urinary incontinence due to ISD, although further research is needed to enhance its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Periurethral skeletal myofibre implantation in patients with urinary incontinence and intrinsic sphincter deficiency: a phase I clinical trial. Yiou, R., Hogrel, JY., Loche, CM., et al.[2015]

A multicenter, placebo-controlled study showed that injecting high doses of autologous skeletal muscle-derived cells significantly improved fecal incontinence (FI) symptoms, particularly in patients with a shorter duration of FI and higher baseline incontinence episode frequency.

The treatment was safe, with no unexpected adverse events reported, and the benefits were sustained or increased over 12 months in the high cell count group, suggesting potential for this therapy in managing FI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skeletal Muscle-Derived Cell Implantation for the Treatment of Fecal Incontinence: A Randomized, Placebo-Controlled Study. Frudinger, A., Gauruder-Burmester, A., Graf, W., et al.[2023]

In a clinical trial involving 39 patients (average age 60.6 years), ultrasound-guided injection of autologous skeletal muscle-derived cells (SMDC) into the external anal sphincter significantly reduced weekly incontinence episodes by at least 50% in 80.6% of males and 78.4% of females after 12 months.

The procedure was well tolerated with no serious adverse events reported, suggesting it is a safe and effective treatment for fecal incontinence due to external anal sphincter damage or atrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skeletal muscle-derived cell implantation for the treatment of sphincter-related faecal incontinence. Frudinger, A., Marksteiner, R., Pfeifer, J., et al.[2019]

Skeletal muscle-derived mononuclear cells (SMDMCs) were successfully incorporated into the urethra of female rats, promoting recovery of the damaged urethral sphincter after stress urinary incontinence surgery.

The SMDMC treatment led to a significant reduction in connective tissue deposition and an increase in muscle content compared to the saline control group, indicating potential efficacy for this novel cell-based therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Periurethral muscle-derived mononuclear cell injection improves urethral sphincter restoration in rats. Turco, MP., de Souza, AB., de Campos Sousa, I., et al.[2018]

The study found that autologous muscle-derived cells for urinary sphincter repair (AMDC-USR) were safe and well-tolerated, with no serious adverse events reported among female subjects with stress urinary incontinence.

Although the primary efficacy results were inconclusive due to a high placebo response rate (90%), post hoc analyses indicated that stricter endpoints might reveal a potential treatment effect, suggesting the need for refined trial designs in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, placebo-controlled clinical trial evaluating the safety and efficacy of autologous muscle derived cells in female subjects with stress urinary incontinence. Jankowski, RJ., Tu, LM., Carlson, C., et al.[2021]

In a study of 58 participants, both autologous muscle-derived cell (AMDC) injections and placebo injections led to significant increases in urethral sphincter volumes and reductions in stress incontinence episode frequency (IEF) after 12 months, but there were no significant differences between the two groups.

Factors such as longer urethral length and larger external sphincter volume at baseline were associated with better responses to AMDC injections, suggesting these may be important predictors of treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the effects of autologous muscle-derived cell injections on urethral sphincter morphometry using 3D/4D ultrasound. Ismail, S., Morin, M., Tu, LM.[2021]

The first clinical trial using autologous muscle-derived stem cells (AMDC) for treating underactive bladder (UAB) showed no adverse events, indicating that the treatment is safe.

After one year, while the patient still required self-catheterization, there was a notable reduction in maximum bladder capacity, suggesting that AMDC injections may improve bladder function in UAB patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder: pilot study. Levanovich, PE., Diokno, A., Hasenau, DL., et al.[2018]

References

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

Safety and Efficacy of Iltamiocel Cellular Therapy for the Treatment of Fecal Incontinence. Results of a Phase 1/2 Study. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Periurethral skeletal myofibre implantation in patients with urinary incontinence and intrinsic sphincter deficiency: a phase I clinical trial. [2015]

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

Skeletal Muscle-Derived Cell Implantation for the Treatment of Fecal Incontinence: A Randomized, Placebo-Controlled Study. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Skeletal muscle-derived cell implantation for the treatment of sphincter-related faecal incontinence. [2019]

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

Periurethral muscle-derived mononuclear cell injection improves urethral sphincter restoration in rats. [2018]

6. Netherlands pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, placebo-controlled clinical trial evaluating the safety and efficacy of autologous muscle derived cells in female subjects with stress urinary incontinence. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Assessment of the effects of autologous muscle-derived cell injections on urethral sphincter morphometry using 3D/4D ultrasound. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder: pilot study. [2018]