EG110A for Neurogenic Detrusor Overactivity

Recruiting at 4 trial locations

Overseen By Cornelia Haag-Molkenteller, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: EG 427

Disqualifiers: Tumor, Malignancy, Active herpes, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

16 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a first-in-human, Phase 1b/2a, open-label, dose-escalation study of a single treatment course consisting of multiple intradetrusor injections of EG110A in male and female adult participants with Neurogenic Detrusor Overactivity (NDO)-related incontinence following Spinal Cord Injury (SCI), who have persistent incontinence after standard of care therapy and who perform Clear Intermittent Catheterization (CIC) on a regular basis.

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, it seems that participants should have been on a stable treatment for Neurogenic Detrusor Overactivity for at least 3 months before joining the trial.

What data supports the effectiveness of the drug EG110A for treating neurogenic detrusor overactivity?

The research shows that treatments like botulinum toxin A, which is similar to EG110A, have been effective in treating neurogenic detrusor overactivity by reducing symptoms and improving bladder control. ^{1 2 3 4 5}

What safety data exists for EG110A in treating neurogenic detrusor overactivity?

The safety of treatments similar to EG110A, like abobotulinumtoxinA and incobotulinumtoxinA, has been studied in patients with neurogenic detrusor overactivity, showing they are generally safe for human use. ^{2 6 7 8 9}

Research Team

Cornelia Haag-Molkenteller, MD

Principal Investigator

EG 427

Eligibility Criteria

This trial is for adults with bladder control issues due to nerve damage from a spinal cord injury, who still have incontinence despite standard treatments and regularly use a catheter. Participants must be stable post-injury and able to attend all study visits.

Inclusion Criteria

I have had urinary incontinence due to nerve damage for at least 3 months.

My spinal cord injury is stable and happened over a year ago.

I have tried treatments for NDO without success or had side effects, and I'm not considering BoNT/A or surgery next.

Exclusion Criteria

I do not currently have active oral or genital herpes, or it has been treated and fully healed.

I had cancer treatment within the last 4 weeks and still have side effects.

I have a tumor or cancer affecting my spine or have another cause for spinal cord injury.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single treatment course consisting of multiple intradetrusor injections of EG110A

12 weeks

Multiple visits for injections and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including urodynamic assessments and bladder diary evaluations

52 weeks

Regular follow-up visits for assessments

Treatment Details

Interventions

• EG110A

Trial Overview The study tests multiple doses of EG110A, given via bladder injections, to see if it can help with incontinence caused by neurogenic detrusor overactivity following spinal cord injury. It's an early-phase trial to find the right dose.

Participant Groups

Group I: EG110A (low dose) Experimental Treatment 1 Intervention

Patients who Received EG110A (low dose)

Group II: EG110A (Middle Dose) Experimental Treatment 1 Intervention

Patients who Received EG110A (middle dose)

Group III: EG110A (High Dose) Experimental Treatment 1 Intervention

Patients who Received EG110A (high dose)

Who Is Running the Clinical Trial?

EG 427

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

Intravesical oxybutynin therapy significantly increased maximum bladder capacity in both children (77.8 ml) and adults (110.8 ml), indicating its effectiveness in treating neurogenic detrusor overactivity.

The treatment was generally safe, with 76.9% of adults and 74.6% of children reporting improvement or being dry after therapy, although 13.5% experienced side effects, and 20.4% discontinued treatment for various reasons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical oxybutynin therapy for patients with neurogenic detrusor overactivity: a systematic review and meta-analysis. Shen, SH., Jia, X., Peng, L., et al.[2022]

In a Phase IIa study involving 47 adult patients with neurogenic detrusor overactivity, abobotulinumtoxinA (Dysport) significantly reduced the frequency of daily incontinence episodes, with improvements seen in both 15 and 30 injection groups.

Dysport also led to significant enhancements in urodynamic parameters, such as maximum cystometric capacity and detrusor pressure, while the safety profile showed some serious adverse events related to muscle weakness, particularly in patients receiving 15 injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of two administration modes of an intra-detrusor injection of 750 units dysport® (abobotulinumtoxinA) in patients suffering from refractory neurogenic detrusor overactivity (NDO): A randomised placebo-controlled phase IIa study. Denys, P., Del Popolo, G., Amarenco, G., et al.[2022]

Repeat botulinum toxin A (BTX-A) injections can provide sustained improvements in quality of life for patients with neurogenic detrusor overactivity (NDO), particularly for those receiving four or fewer injections, based on a review of 18 studies involving 1533 patients.

The study found a low rate of adverse events associated with repeat BTX-A injections, indicating that the treatment is generally safe; however, quality of life may decline for patients receiving five or more injections, highlighting the need for further research on long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is repeat Botulinum Toxin A injection valuable for neurogenic detrusor overactivity-A systematic review and meta-analysis. Ni, J., Wang, X., Cao, N., et al.[2019]

In a study of 62 spinal cord injury patients who switched from Onabotulinumtoxin A (OTA) to Abobotulinumtoxin A (ATA) for treating neurogenic detrusor overactivity, 28.9% initially responded to ATA injections, with 14.5% maintaining response after a median follow-up of 17 months.

The switch to ATA may provide long-term efficacy for some patients and potentially delay the need for surgical interventions like augmentation enterocystoplasty, as 51.6% of patients were either awaiting or had undergone this surgery during the follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switching from onabotulinum toxin A to abobotulinum toxin A for treating detrusor overactivity in spinal cord injured patient, does it really work? Le Roy, C., Lefèvre, C., Lepoittevin, L., et al.[2023]

In a study of 214 patients with neurogenic detrusor overactivity (NDO), Botox therapy significantly improved bladder function, as shown by increased maximum detrusor pressure and capacity, and reduced urinary incontinence episodes.

Post-treatment, the incidence of urinary tract infections (UTIs) and the use of incontinence aids dropped significantly, leading to lower healthcare costs for patients, demonstrating the economic benefits of Botox therapy in managing NDO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment outcomes and resource use of patients with neurogenic detrusor overactivity receiving botulinum toxin A (BOTOX) therapy in Germany. Wefer, B., Ehlken, B., Bremer, J., et al.[2021]

In a study involving 836 participants over 12 weeks, both 4 mg and 8 mg doses of fesoterodine significantly improved symptoms of overactive bladder compared to placebo, including reductions in urinary frequency and urgency.

Fesoterodine was well tolerated, with common side effects being dry mouth, constipation, and urinary tract infections, but overall, the treatment showed a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety and tolerability of fesoterodine for overactive bladder syndrome. Nitti, VW., Dmochowski, R., Sand, PK., et al.[2007]

In a study involving 57 children aged 6 to 15 with neurogenic detrusor overactivity, both transdermal and oral oxybutynin significantly improved urine volume, with transdermal oxybutynin showing a mean increase from 95 ml to 125 ml and oral oxybutynin from 114 ml to 166 ml.

Transdermal oxybutynin was found to be well tolerated with fewer side effects compared to oral oxybutynin, indicating it may be a safer alternative for children who have previously used oxybutynin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of transdermal and oral oxybutynin in children with neurogenic detrusor overactivity. Cartwright, PC., Coplen, DE., Kogan, BA., et al.[2013]

In a study involving 420 patients with urge urinary incontinence, individualized dosing of extended-release oxybutynin led to a significant reduction in incontinence episodes, with an average decrease of 79.3% in total episodes and 83.2% in urge episodes.

The treatment was well tolerated, with 81% of patients experiencing at least a 70% reduction in incontinence episodes and 43% achieving total dryness, although 23% reported moderate to severe dry mouth as a side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of extended release oxybutynin for the treatment of urge incontinence: an analysis of data from 3 flexible dosing studies. MacDiarmid, SA., Anderson, RU., Armstrong, RB., et al.[2019]

In a pilot study of 17 male patients with neurogenic detrusor overactivity, incobotulinumtoxinA injections led to significant improvements in daily urinary frequency (from 9.4 to 4.6) and daily incontinence episodes (from 2.5 to 0.4), indicating its efficacy in managing symptoms of urgency incontinence.

No serious safety concerns were reported, as there were no urinary tract infections or new urinary retention cases within 30 days post-injection, suggesting that incobotulinumtoxinA is a safe treatment option for neurogenic bladder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The intravesical injection of highly purified botulinum toxin for the treatment of neurogenic detrusor overactivity. Asafu-Adjei, D., Small, A., McWilliams, G., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Intravesical oxybutynin therapy for patients with neurogenic detrusor overactivity: a systematic review and meta-analysis. [2022]

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

Efficacy and safety of two administration modes of an intra-detrusor injection of 750 units dysport® (abobotulinumtoxinA) in patients suffering from refractory neurogenic detrusor overactivity (NDO): A randomised placebo-controlled phase IIa study. [2022]

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

Is repeat Botulinum Toxin A injection valuable for neurogenic detrusor overactivity-A systematic review and meta-analysis. [2019]

4. France pubmed.ncbi.nlm.nih.gov

Switching from onabotulinum toxin A to abobotulinum toxin A for treating detrusor overactivity in spinal cord injured patient, does it really work? [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Treatment outcomes and resource use of patients with neurogenic detrusor overactivity receiving botulinum toxin A (BOTOX) therapy in Germany. [2021]

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

Efficacy, safety and tolerability of fesoterodine for overactive bladder syndrome. [2007]

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

Efficacy and safety of transdermal and oral oxybutynin in children with neurogenic detrusor overactivity. [2013]

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

Efficacy and safety of extended release oxybutynin for the treatment of urge incontinence: an analysis of data from 3 flexible dosing studies. [2019]

9. Canada pubmed.ncbi.nlm.nih.gov

The intravesical injection of highly purified botulinum toxin for the treatment of neurogenic detrusor overactivity. [2021]