Study to assess the safety and efficacy of multipotent mesenchymal stem cells administration as a treatment for patients with faecal incontinence.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Publica Andaluza Para La Investigacion De Malaga En Biomedicina Y Salud

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]

Decision date (initial)

2024-12-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515766-13-00

EudraCT number

2021-002331-34

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the safety and efficacy, as well as to determine the best regenerative treatment dose with allogeneic adult mesenchymal stem cells from adipose tissue (AMSCs), conditioned in a hyaluronic acid matrix, administered intralesionally in patients with faecal incontinence.

Secondary objectives 5

1. To confirm the safety of using the two doses of allogeneic AMSCs (60 and 120 million ADSCs) at 18 and 24 months after administration.
2. To evaluate the efficacy of intralesional administration of the two different doses (60 million and 120 million) of allogeneic dATMCs as therapy for FI, compared to placebo and hyaluronic acid hydrogel at 18 and 24 months after administration.
3. To establish the most efficient dose of ADSCs in the treatment of structural faecal incontinence.
4. To assess the feasibility of the therapy administered. To determine whether the administration of the cell/comparator product was carried out correctly, without incidents or complications.
5. The results in the experimental groups will be compared with the values obtained in the groups treated with the comparators (placebo and acellular matrix), in a blinded manner to determine the effect of the intervention on these parameters.

Conditions and MedDRA coding

Fecal incontinence

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age 18-80 years (both inclusive), male or female.
2. A single internal and/or external sphincter defect, not more than 140 degrees, at any level of the anal canal. Therefore, the following may be included - Patients with a single external sphincter defect equal to or less than 140 degrees without or with an associated internal defect (in this case the degree of separation of the internal sphincter does not matter). - Patients with no external sphincter defect and a single internal sphincter defect equal to or less than 140 degrees.The internal defect will be used for treatment.
3. Fecal incontinence severity of 12 or more on the Wexner Test and/or at least 6 episodes of fecal incontinence over at least a 21-day period, recorded in the Patient Diary.
4. Duration of fecal incontinence for at least 1 year prior to inclusion.
5. Informed consent obtained in writing.
6. Commitment to use an effective contraceptive method, both in men and women, during the entire follow-up period of the clinical trial**. **Effective contraception for women is described as an oral contraceptive method (combining estrogens with gestagens) or another type of contraception, such as an injectable, implantable or patch hormonal contraceptive, IUD or surgical sterilization. The combined use of a condom plus a spermicidal cream is described as an effective contraceptive method for men.

Exclusion criteria 17

1. Have been previously treated with: • Perianal bulking agents: dextranomer in stabilized hyaluronic acid (NASHA Dx), silicone material (PTQ™), autologous fat, Teflon, bovine glutaraldehyde cross-linked collagen, carbon-coated zirconium beads, polydimethylsiloxane elastomer, polyacrylamide cross-linked hydrogel, porcine dermal collagen, synthetic calcium hydroxyapatite ceramic microspheres or polyacrylonitrile cylinders.
2. Anorectal tumors at the time of inclusion.
3. Patients with active perianal diseases at the time of inclusion: fissure, fistula, venereal disease and abscess.
4. Anorectal stenosis, which prevents the performance of ultrasound.
5. Significant chronic anorectal or pelvic pain (moderate to severe pain according to VAS scale)
6. Pregnant women or in the 6 months postpartum.
7. Medical history of Human Immunodeficiency Virus (HIV) infection or any severe immunocompromised state or administration of immunosuppressive therapy.
8. Malignancies in remission for less than one year prior to study. An exception to the requirement is basal cell carcinoma (BCC). BCC in "remission" for less than one year is not an exclusion criterion, provided the BCC has been treated and there is no evidence of active disease.
9. Patients with a pathology or clinical condition that prevents the administration of anesthesia and the performance of the intervention in the opinion of the anesthesiologist (eg hemorrhagic diathesis, thrombocytopenia or anticoagulant therapy).
10. Chemotherapy during the 6 months prior to the time of inclusion.
11. Prior radiation with evidence of radiation injury to the area to be treated.
12. Participation in any other clinical study during the 3 months prior to the pre-selection visit, as well as during the execution of the trial.
13. Patients with other serious conditions, anticipated to be unreliable, or otherwise not suitable for participation in the investigator's judgment (eg, severe psychiatric illness or other illness that precludes or does not ensure adequate patient follow-up).
14. Patients with inflammatory or autoimmune disease, uncontrolled or controlled with immunosuppressants or immunomodulators. For biological antibody type treatment it will be consulted specifically the drug and the pathology with preclinical and clinical coordinators.
15. Patients with active infection by virus B, virus C or syphilis
16. Patients who require a surgical procedure related to the sphincter apparatus at the time of inclusion
17. Patients with uncontrolled diarrhea or secondary to a process diagnosed as collagenous colitis, inflammatory disease, etc., at the time of inclusion. Patients with chronic constipation who require taking laxatives at the time of inclusion.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. A) Safety variables: All clinical adverse events will be collected during follow-up at the same times as the clinical assessment. The cumulative incidence of adverse events attributed to study therapy at 12 months post-treatment will be assessed as the primary endpoint.
2. B) Variables that measure clinical efficacy by assessing the severity of incontinence: Changes from baseline (pre-implantation) measurement of:
3. Jorge-Wexner test score. Scales for assessing the degree of incontinence are numerous and vary in complexity. The Jorge-Wexner test provides a simple and objective assessment of both stool characteristics and frequency of incontinence episodes, where 0 represents perfect continence and 20 represents the highest degree of incontinence. It will be calculated preoperatively and when appropriate according to visits.
4. Number of episodes of faecal incontinence of loose or solid stools (based on data from the patient's defecation diary).
5. Score on the faecal incontinence quality of life scale, a survey validated by the American Association of Colorectal Surgeons and recently by the Spanish Digestive Surgeons, which has been adapted and validated in its Spanish version. The 29 questions are divided into 4 different health domains: lifestyle, behaviour, depression/self-perception and embarrassment. Responses to each question are scored from 1 to 5, with 1 indicating the worst quality of life status.
6. Anal manometry: Measures the anal pressure profile using a manometer. Parameters of interest (mm Hg): Maximum basal pressure, maximum voluntary contraction pressure, anal canal length, inhibitory recto-anal reflex, rectal sensitivity. It will be used to know the basal pressure state of the patient's sphincter and rectal complex, and thus be able to compare these parameters after treatment, allowing us to know if it has had any impact and where (sphincter or rectal sensitivity).

Secondary endpoints 4

1. A) Other clinical efficacy variables (imaging variables): 3D endorectal ultrasound: a ir prminimally invasive scan that allows ultrasound imaging of the layers of the rectal wall, anal sphincters and the organs around the rectum and anus, and allows ultrasound monitoring of lesions and theognostic evolution. It is performed according to Starck's classification. Proctoscopy: Inflammation, ulceration, normal. Rectoscopy: Inflammation, ulcer, normal.
2. B) Efficacy variables for analysis purposes: Changes in the use of continence-enhancing drugs: the use of continence-enhancing drugs will be collected in the CRD to assess the differences between the two groups with respect to the following parameters: 1 Number of patients reaching the clinical condition that enables withdrawal of previously prescribed continence-enhancing drugs. Time to reach this condition
3. B) Efficacy variables for analysis purposes: Changes in the use of continence-enhancing drugs: the use of continence-enhancing drugs will be collected in the CRD to assess the differences between the two groups with respect to the following parameters: 2 Number of patients who need to initiate the administration of continence-enhancing drugs during follow-up, if they were not prescribed at inclusion. Time to reach this condition
4. C) Therapy feasibility variable: • It will be collected in the CRD if the procedure of administration of the cellular product/comparator, was performed correctly, without incidences or complications, recording in the same any incidence or complication that took place.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Publica Andaluza Para La Investigacion De Malaga En Biomedicina Y Salud

Sponsor organisation

Fundacion Publica Andaluza Para La Investigacion De Malaga En Biomedicina Y Salud

Address

Calle De Severo Ochoa 35, Parque Tecnologico De Andalucia Parque Tecnologico De Andalucia

City

Malaga

Postcode

29590

Country

Spain

Scientific contact point

Organisation

Fundacion Publica Andaluza Para La Investigacion De Malaga En Biomedicina Y Salud

Contact name

Rocio Moreno

Public contact point

Organisation

Fundacion Publica Andaluza Para La Investigacion De Malaga En Biomedicina Y Salud

Contact name

Rocio Moreno

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications