Cell-Based Therapy for Stress Urinary Incontinence

(CELLEBRATE Trial)

Not currently recruiting at 23 trial locations

Overseen By Ervin Mazniku, M.D., M.Sc.

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Cook MyoSite

Must not be taking: Anticholinergics, Antidepressants, Diuretics, others

Disqualifiers: Urge incontinence, BMI ≥ 35, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AMDC-USR (iltamiocel), which uses cell injections to reduce episodes of stress urinary incontinence (SUI). The goal is to determine if it works better than a placebo (a harmless, inactive treatment) for women who continue to experience SUI after surgery. Women with SUI symptoms for at least six months who have tried surgery but still struggle might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

You may need to stop or adjust your current medications if they affect lower urinary tract function. If you are taking such medications, you must be on a stable dose for at least 2 weeks before the trial and maintain it during the study.

Will I have to stop taking my current medications?

The trial requires that if you are taking medications that affect urinary function, like certain antidepressants or diuretics, you must be on a stable dose for at least 2 weeks before screening and throughout the study. If you can't maintain a stable dose, you may need to stop or adjust your medication.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that AMDC-USR (iltamiocel), which uses a patient's own muscle cells to repair the urinary sphincter, is generally safe. Studies have found no major side effects in those who received this treatment. For example, one study reported that various doses of these cells were well-tolerated, with no significant treatment-related problems. Another study followed patients for 12 months and also found no major safety issues. Overall, the evidence suggests that this cell-based therapy is safe for treating stress urinary incontinence. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for stress urinary incontinence, which typically involve pelvic floor exercises, medications, or surgical interventions, iltamiocel offers a novel approach by using autologous muscle-derived cells to repair the urinary sphincter. This cell-based therapy targets the underlying issue by potentially regenerating damaged muscle tissue, which could provide a more permanent solution compared to temporary symptom management. Researchers are excited about iltamiocel because it harnesses the body's own cells, reducing the risk of rejection and potentially improving long-term outcomes for patients suffering from this condition.

What evidence suggests that AMDC-USR (iltamiocel) might be an effective treatment for stress urinary incontinence?

Research suggests that using a person's own muscle cells (AMDC-USR) might help reduce symptoms of stress urinary incontinence (SUI). Previous studies have shown that these cells can be safely used to repair the muscles controlling urination. In this trial, some participants will receive AMDC-USR. Past studies indicated that some patients experienced fewer incontinence episodes after receiving AMDC-USR. Although one study did not definitively prove its effectiveness, it provided valuable insights for future research. Overall, the outlook is positive, but more data is needed to fully understand its potential. ^{1 2 3 4 6}

Who Is on the Research Team?

Melissa Kaufman, M.D., Ph.D.

Principal Investigator

Vanderbilt University Medical Center, Department of Urologic Surgery

Are You a Good Fit for This Trial?

This trial is for adult women over 18 who have moderate-to-severe stress urinary incontinence despite having surgery for it. They must not be pregnant, planning pregnancy, or breastfeeding, and should not have a BMI of 35 or higher. Participants need to have tried other treatments like pelvic exercises and cannot be on certain medications affecting the bladder.

Inclusion Criteria

I am a woman over 18 with severe bladder control issues for 6+ months.

Must have completed 100% of the screening 3-day diary evening reports

I have had surgery for stress urinary incontinence before.

Exclusion Criteria

My BMI is 35 or higher.

I have experienced stress urinary incontinence for less than 6 months.

My medication for urinary tract issues has been stable for at least 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive injections of either AMDC-USR or placebo for urinary sphincter repair

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 after the blinded portion

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• AMDC-USR (iltamiocel)
• Placebo

Trial Overview The study tests Autologous Muscle Derived Cells (AMDC-USR) against a placebo in reducing stress incontinence episodes. Women will randomly receive either cell injections or a placebo to see which is more effective at treating their condition after previous surgeries failed.

How Is the Trial Designed?

Group I: AMDC-USR (iltamiocel) Experimental Treatment 1 Intervention

Autologous muscle-derived cells for urinary sphincter repair (AMDC-USR; generic name: iltamiocel) is the study product.

Group II: Placebo Placebo Group 1 Intervention

Placebo control is the vehicle solution used for the study product.

Who Is Running the Clinical Trial?

Cook MyoSite

Lead Sponsor

Trials

14

Recruited

1,100+

Published Research Related to This Trial

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]

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]

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]

Stress urinary incontinence affects a significant portion of the population, particularly the elderly, with around 25% of seniors experiencing this condition due to degeneration of the sphincter muscle.

Cell-based therapies using stem cells, such as mesenchymal stromal cells and urine-derived stem cells, show promise in improving sphincter muscle function when other treatments fail, and advancements in surgical techniques and evaluation methods are being developed to enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards a Treatment of Stress Urinary Incontinence: Application of Mesenchymal Stromal Cells for Regeneration of the Sphincter Muscle. Aicher, WK., Hart, ML., Stallkamp, J., et al.[2020]

In a clinical trial involving 20 patients with underactive bladder (UAB), intradetrusor injections of Autologous Muscle Derived Cells (AMDC) showed promising safety and efficacy, with 58% of patients reporting significant improvement in symptoms at 12 months post-treatment.

No serious adverse events were reported, and improvements included reduced post-void residual urine volume and increased voiding efficiency, suggesting that AMDC therapy could be a viable option for patients with chronic urinary retention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved global response outcome after intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder. Gilleran, J., Diokno, AC., Ward, E., et al.[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]

Autologous mesenchymal-derived stem cells (AMDC) have shown an 80% improvement in urinary incontinence symptoms for both men and women, indicating their efficacy as a treatment for stress urinary incontinence (SUI).

The precision of cell injection is crucial for treatment success, and using robotic-assisted systems for endoscopic procedures may enhance the effectiveness of AMDC treatments by ensuring accurate placement of the injected cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regenerative medicine- techniques and methods of administering autologous derived stem cells in urinary incontinence. Stangel-Wojcikiewicz, K., Petko, M., Kobus, K., et al.[2018]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24582537/

Autologous muscle derived cells for treatment of stress ... Conclusions: Autologous muscle derived cells for urinary sphincter repair at doses of 10, 50, 100 and 200×10(6) cells appears safe. Efficacy data suggest a ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022534714003024

Autologous Muscle Derived Cells for Treatment of Stress ... We assess the 12-month safety and potential efficacy of autologous muscle derived cells for urinary sphincter repair (Cook MyoSite Incorporated, Pittsburgh, ...

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/j.1757-5672.2009.00032.x

Muscle‐derived Stem Cell Therapy for Stress Urinary ... The aim of the present article is to overview the potential of muscle-derived stem cells and other cellular therapy for urethral ...

4. auajournals.org auajournals.org/doi/pdf/10.1016/j.juro.2014.02.047

Autologous Muscle Derived Cells for Treatment of Stress ... Conclusions: Autologous muscle derived cells for urinary sphincter repair at doses of 10, 50, 100 and 200 106 cells appears safe. Efficacy data suggest a ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30324580/

A double-blind, randomized, placebo-controlled clinical ... Conclusions: Although the primary efficacy finding was inconclusive, these results inform future trial design of AMDC-USR to identify clinically meaningful ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23260547/

Autologous muscle derived cell therapy for stress urinary ... Injection of autologous muscle derived cells in a wide range of doses appears safe with no major treatment related adverse events reported.