Derived cell ATMP implantation for the treatment of fecal incontinence: a multicentre, randomized, double-blind, placebo-controlled, parallel-group, dose-finding clinical study.
CASE STUDY TYPE
ATMP interventional clinical trial in Gastro-Enterology (phase II – EU)
Fecal incontinence (FI) is a common disease and can be a devastating social disability. It can lead to a loss of self-esteem, social isolation, and a diminished quality of life. FI affects people of all ages, but its prevalence is disproportionally higher in women, in the elderly, and in nursing home residents. Conservative treatments like modification of diet, biofeedback, loperamide hydrochloride, or estrogen replacement may show an insufficient long-term efficacy and surgical treatment offered to patients with severe FI shows not satisfactory long-term results and total continence can usually not be achieved.
Cell-based therapy with autologous myoblasts and fibroblasts injected into the sphincter is an innovative and promising new therapy for the treatment of IF. Once implanted this ATMP, is able to regenerate or enhance the biological function of the dysfunctional tissue. It has already shown positive results in stress urinary incontinence in a phase I trial. It is safe and well tolerated.
The aim of this clinical trial was to find the optimal cell count for functional regeneration of the external anal sphincter in female and male patients with FI.
This was a phase IIb, multinational, multicentre, randomized, double-blind, dose-finding, placebo-controlled study with a parallel group design with 3 treatments:
- Low cell count group
- High cell count group
- Placebo group (cell-free suspension)
- Determine change in incontinence episode frequency (IEF) at day 180 from baseline.
- Evaluate change in the Wexner score
- Assess the Visual Analogue Scale
- Evaluate anorectal manometry data
- Document patient-reported quality of life.
SCIENTIFIC and DATA VALORISATION
- Trial results used for the ATMP marketing authorisation and further Phase II design
Key factors of success
- ICTA’s capability to adapt to new regulatory procedure (project started in 2012)
- ICTA’s responsiveness and ability to develop adapted IT tool
- ICTA’s flexibility to manage additional statistical analyses
LESSONS LEARNED to speed up the start-up phase of the next study
- Importance of close collaboration between ICTA and Sponsor especially in the context of a rescue study
- Active involvement of the Sponsor during the study to maintain the centres’ commitment
- Optimal project coordination: Timelines, logistics, sub-contractors management, reporting tools implementation, events management.
|KEY CHALLENGES||ICTA’s SOLUTIONS||ICTA’s ACHIEVEMENTS|
|Rescue project and|
long delay before Sponsor decides to reactivate the project
|Pro-active communication with the sponsor on bi-weekly basis during the handover|
Complete quality check of the TMF
And key study documents to be consistent with trial objectives
|Successful project including complete Clinical Study Report (CSR) used to obtain ATMP market approval in Europe|
|ATMP logistics and regulatory procedures|
9 participating countries and 1 laboratory producing the autologous cells
|Development of a specific IT tool for a smooth workflow of the ATMP from site to sponsor and sponsor to site.||3 inspections performed by the Regulatory Authorities in 3 different countries|
➔ 0 critical finding
|Sites recruitment due to ATMP regulatory procedure to respect|
Product and fecal sample management
|Selection of back-up countries|
Assessment of each site facilities and level of staffing to facilitate patient recruitment
|99.6% of the originally planned patients were recruited|
|Multiple statistical analyses requested after project re-start||Statistical analysis plan (SAP) check and completed by additional subgroups analyses|
Update of the statistical program
|TFLs provided within timelines to Sponsor|
Enabling data valorization within the CSR writing and marketing authorisation dossier