A Phase 2a Study To Evaluate VMB-100 In Females With Stress Urinary Incontinence

Stress Urinary Incontinence Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06247241
• Other study ID #: VMB-100-U222
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 2024
• Est. completion date: November 2027

Study information

• Verified date: January 2024
• Source: Versameb AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: November 2027
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Enuresis
• Stress Urinary Incontinence
• Urinary Incontinence
• Urinary Incontinence, Stress

Intervention

Drug:
• VMB-100
VMB-100 is administered as intrasphincteric injection in the urethra sphincter

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Versameb AG	PPD

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Efficacy; effect on incontinence event frequency	bladder diary will record number of incontinence events for 7 days prior to each visit	from baseline/preinjection through study completion (est average 1 year)
Other	Efficacy; effect on patient assessment of effect	patient reported outcomes questionnaire Patient Global Impression of Severity (PGI-S) for stress urinary incontinence	from baseline/preinjection through study completion (est average 1 year)
Other	Efficacy; effect on patient assessment of effect	patient reported outcomes questionnaire Patient Global Impression of Improvement (PGI-I ) for stress urinary incontinence	from baseline/preinjection through study completion (est average 1 year)
Other	Efficacy; effect on patient assessment of effect	patient reported outcomes questionnaire; International Consultation on Incontinence Questionnaire (ICIQ)	from baseline/preinjection through study completion (est average 1 year)
Other	Efficacy; effect on patient assessment of effect	patient reported outcomes questionnaire Kings Health Questionnaire (KHQ)	from baseline/preinjection through study completion (est average 1 year)
Other	Pharmacodynamic evaluation; morphologic changes to the urethra sphincter using transvaginal ultrasound	change in sphincter thickness, measured in millimeters	from baseline/preinjection to week 24
Primary	Safety following VMB-100 administration	Adverse Events (AEs)	from baseline/preinjection through study completion (est average 1 year)
Primary	Safety following VMB-100 administration	Treatment Emergent Adverse Events (TEAEs)	immediately after the intervention through study completion (est average 1 year)
Primary	Safety following VMB-100 administration	Adverse Events of Special Interest (AESIs)	immediately after the intervention through study completion (est average 1 year)
Primary	Tolerability of VMB-100 injection, pain	measurement of pain by Visual Analogue Scale (0-10, where 0 is no pain and 10 is the worst pain)	periprocedurally
Primary	Vital signs following VMB-100 administration	heart rate, blood pressure, respiratory rate, body temperature	from baseline/preinjection through study completion (est average 1 year)
Primary	12-lead ECG following VMB-100 administration	P-wave, QRS complex, QTc prolongation	from baseline/preinjection through study completion (est average 1 year)
Primary	Clinical laboratory measurements following VMB-100 administration	change in hematology parameters ( proportion of subjects)	from baseline/preinjection through study completion (est average 1 year)
Primary	Clinical laboratory measurements following VMB-100 administration	change in biochemistry parameters (proportion of subjects)	from baseline/preinjection through study completion (est average 1 year)
Primary	Clinical laboratory measurements following VMB-100 administration	change in urinalysis (proportion of subjects)	from baseline/preinjection through study completion (est average 1 year)