Clinical trial NCT06247241: A Phase 2a Study To Evaluate VMB-100 In Females With Stress Urinary Incontinence
Official title: A Phase 2a, Open-Label, First-In-Human, Two-Part, Single And Multiple Ascending Dose Study To Evaluate The Safety, Tolerability, And Efficacy Of VMB-100 In Female Subjects With Moderate Stress Urinary Incontinence
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Stress Urinary Incontinence
Lead sponsor: Versameb AG
Sponsor class: INDUSTRY
Collaborators: name: PPD Development, LP
First posted: 2024-02-07
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Single and multiple ascending dose
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Safety following VMB-100 administration
timeFrame: from baseline/preinjection through study completion (est average 1 year)
measure: Safety following VMB-100 administration
timeFrame: immediately after the intervention through study completion (est average 1 year)
measure: Safety following VMB-100 administration
timeFrame: immediately after the intervention through study completion (est average 1 year)
measure: Tolerability of VMB-100 injection, pain
timeFrame: periprocedurally
measure: Vital signs following VMB-100 administration
timeFrame: from baseline/preinjection through study completion (est average 1 year)
measure: 12-lead ECG following VMB-100 administration
timeFrame: from baseline/preinjection through study completion (est average 1 year)
measure: Clinical laboratory measurements following VMB-100 administration
timeFrame: from baseline/preinjection through study completion (est average 1 year)
measure: Clinical laboratory measurements following VMB-100 administration
timeFrame: from baseline/preinjection through study completion (est average 1 year)
measure: Clinical laboratory measurements following VMB-100 administration
timeFrame: from baseline/preinjection through study completion (est average 1 year)
Secondary outcomes:
Other outcomes:
measure: Efficacy; effect on incontinence event frequency
timeFrame: from baseline/preinjection through study completion (est average 1 year)
measure: Efficacy; effect on patient assessment of effect
timeFrame: from baseline/preinjection through study completion (est average 1 year)
measure: Efficacy; effect on patient assessment of effect
timeFrame: from baseline/preinjection through study completion (est average 1 year)
measure: Efficacy; effect on patient assessment of effect
timeFrame: from baseline/preinjection through study completion (est average 1 year)
measure: Efficacy; effect on patient assessment of effect
timeFrame: from baseline/preinjection through study completion (est average 1 year)
measure: Pharmacodynamic evaluation; morphologic changes to the urethra sphincter using transvaginal ultrasound
timeFrame: from baseline/preinjection to week 24
Locations:
Study officials:
References: