Stress Urinary Incontinence
Conditions
Brief summary
The study drug VMB-100 is an mRNA encoding for IGF-1. It is administered by injection into the urethra sphincter, and taken up by the muscle cells. The IGF-1 acts to promote muscle regeneration in the sphincter, which is expected to improve the function of the sphincter and thereby alleviate incontinence (urinary leakage).
Detailed description
Versameb AG (Sponsor) is developing VMB-100 for the treatment of stress urinary incontinence (SUI), and mixed urinary incontinence (MUI) with a predominant stress component, a common and debilitating condition that significantly impacts quality of life, and for which there are currently no approved pharmacological therapies available in the US. The drug substance of VMB-100 is a mRNA encoding human insulin-like growth factor-1 (IGF-1). VMB-100 is administered as a transurethral injection into the urinary sphincter muscle. The injected mRNA is taken up by the muscle tissue cells and serves as a template for the translation of the protein IGF-1. Insulin-like growth factor-1 is secreted into the extracellular space, where it acts to promote muscle regeneration of the urinary sphincter via auto- and paracrine activation of downstream pathways in a localized manner. The current understanding in urology is that reduced maximum urethral closure pressure (MUCP) is the factor most strongly associated with SUI. This implies that improving function of the closure muscles would have therapeutic merit in both SUI as well as MUI with a predominant stress component. No treatment which restores the physiology (regenerates the urinary sphincter muscle) is currently available. Given IGF-1's role in regenerating/maintaining muscle tissue women with SUI may benefit from a localized increase in IGF-1 levels in the urinary sphincter to regenerate muscle and restore sphincter function, thus alleviating the incontinence.
Interventions
DRUGVMB-100
VMB-100 is administered as intrasphincteric injection in the urethra sphincter
Sponsors
PPD Development, LP
Versameb AG
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single and multiple ascending dose
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
Main inclusion criteria: * Pre- or peri-menopausal female subject between 18 and 55 years of age * Body mass index (BMI) of 19 to 35 kg/m2 * Active SUI of moderate severity for at least 6 consecutive months documented in medical history * Refractory to standard of care measures * Must not be pregnant, lactating, or actively trying to become pregnant. Main
Exclusion criteria
* Any concurrent condition or any clinically significant abnormality at Screening which in the opinion of the Investigator may affect the interpretation of safety or efficacy data or which otherwise contradicts participation in a clinical study with VMB-100 * Unwilling to undergo transvaginal sonography or cystoscopy * Urodynamic detrusor overactivity * History of urinary urge incontinence of neurogenic etiology. * History of or planning for pelvic radiation. * History of use of any bulking agent or Botox to treat SUI in the past 12 month. * History of urethral sling, anterior prolapse repair, and/or other SUI procedures or surgical procedures affecting continence. * Taking any medications that are known to have an effect on urinary continence or medications that may exacerbate incontinence
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical laboratory measurements following VMB-100 administration | from baseline/preinjection through study completion (est average 1 year) | change in hematology parameters ( proportion of subjects) |
| Tolerability of VMB-100 injection, pain | periprocedurally | measurement of pain by Visual Analogue Scale (0-10, where 0 is no pain and 10 is the worst pain) |
| Vital signs following VMB-100 administration | from baseline/preinjection through study completion (est average 1 year) | heart rate, blood pressure, respiratory rate, body temperature |
| 12-lead ECG following VMB-100 administration | from baseline/preinjection through study completion (est average 1 year) | P-wave, QRS complex, QTc prolongation |
| Safety following VMB-100 administration | from baseline/preinjection through study completion (est average 1 year) | Adverse Events (AEs) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Efficacy; effect on patient assessment of effect | from baseline/preinjection through study completion (est average 1 year) | patient reported outcomes questionnaire Patient Global Impression of Severity (PGI-S) for stress urinary incontinence |
| Pharmacodynamic evaluation; morphologic changes to the urethra sphincter using transvaginal ultrasound | from baseline/preinjection to week 24 | change in sphincter thickness, measured in millimeters |
| Efficacy; effect on incontinence event frequency | from baseline/preinjection through study completion (est average 1 year) | bladder diary will record number of incontinence events for 7 days prior to each visit |
Outcome results
None listed