Clinical Trials Register

Summary
EudraCT Number:	2022-003197-23
Sponsor's Protocol Code Number:	PB_A&A-ASC-FISTULA_1.0
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2023-01-17
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2022-003197-23

A.3

Full title of the trial

Multicenter, controlled, randomized clinical trial comparing the efficacy of auto- and allogeneic mesenchymal stromal cells in the healing of Crohn-related anal fistulas

Wieloośrodkowe, kontrolowane, randomizowane badanie kliniczne porównujące skuteczność auto- i allogenicznych mezenchymalnych komórek stromalnych w gojeniu przetok odbytu powstałych w przebiegu choroby Leśniowskiego i Crohna

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Multicenter, controlled, randomized clinical trial comparing the efficacy of auto- and allogeneic mesenchymal stromal cells in the healing of Crohn-related anal fistulas

A.3.2

Name or abbreviated title of the trial where available

A&A-ASC-FISTULA

A.4.1

Sponsor's protocol code number

PB_A&A-ASC-FISTULA_1.0

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Jagiellonian University - Medical College
B.1.3.4	Country	Poland
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Agencja Badań Medycznych
B.4.2	Country	Poland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Jagiellonian University - Medical College
B.5.2	Functional name of contact point	Biuro ds. Badań Klinicznych
B.5.3	Address:
B.5.3.1	Street Address	ul. Podwale 3/6, room 5
B.5.3.2	Town/ city	Kraków
B.5.3.3	Post code	31-118
B.5.3.4	Country	Poland
B.5.4	Telephone number	+48123704330
B.5.6	E-mail	badania.kliniczne@uj.edu.pl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Auto-ASC
D.3.2	Product code	Auto-ASC
D.3.4	Pharmaceutical form	Dispersion for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Soft tissue use (Noncurrent) Submucosal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	auto-ASC
D.3.9.2	Current sponsor code	auto-ASC
D.3.9.3	Other descriptive name	Autologous adipose tissue-derived mesenchymal stem cells
D.3.9.4	EV Substance Code	SUB196997
D.3.10	Strength
D.3.10.1	Concentration unit	million organisms/ml million organisms/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	9 to 11
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Yes
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Allo-ASC
D.3.2	Product code	Allo-ASC
D.3.4	Pharmaceutical form	Dispersion for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Soft tissue use (Noncurrent) Submucosal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	allo-ASC
D.3.9.2	Current sponsor code	allo-ASC
D.3.9.3	Other descriptive name	Allogeneic adipose-derived mesenchymal stem cells
D.3.9.4	EV Substance Code	SUB284526
D.3.10	Strength
D.3.10.1	Concentration unit	million organisms/ml million organisms/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	9 to 11
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Yes
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection/infusion
D.8.4	Route of administration of the placebo	Submucosal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Anal or recto-cutaneous or recto-vaginal Crohn-related fistula

Przetoka odbytu lub odbytniczo-skórna lub odbytniczo-pochwowa powstałe w przebiegu choroby Leśniowskiego i Crohna

E.1.1.1

Medical condition in easily understood language

Anal or recto-cutaneous or recto-vaginal Crohn-related fistula

Przetoka odbytniczo-skórna, odbytniczo-pochowa lub przetoka odbytu powstałe w przebiegu choroby Leśniowskiego i Crohna

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10002156
E.1.2	Term	Anal fistula
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The evaluation of the clinical efficacy of recto-cutaneous and recto-vaginal Crohn-related fistulas treated by auto- or allogeneic mesenchymal stem / stromal cells in comparison to placebo.
1. Percentage of healed fistulas at months 3 and 6 after intervention (I2) in the ASC groups (auto- and allogeneic) in relation to the placebo group.
2. Percentage of healed fistulas at month 12 (late healing) from intervention (I2) in the ASC groups (auto- and allogeneic) compared to the placebo group.
3. The rate of remission (resolution of active fistula symptoms) at months 3 and 6 after intervention (I2) in the ASC groups (auto- and allogeneic) compared to the placebo group.
4. Rate of remission (resolution of active fistula symptoms) at month 12 after intervention (I2) in the ASC groups (auto- and allogeneic) compared to the placebo group.
5. Relapse rate at month 12 after intervention (I2) in the ASC groups (auto- and allogeneic) compared to the placebo group.

Ocena skuteczności leczenia przetok odbytniczo-skórnych i odbytniczo-pochwowych powstałych w przebiegu ch. Crohna poprzez stosowanie auto- lub allogenicznych ASC w odniesieniu do placebo.
1.Odsetek wygojonych przetok w 3 i 6 miesiącu od interwencji w grupach otrzymujących ASC (autologiczne i allogeniczne) w odniesieniu do grupy placebo.
2.Odsetek wygojonych przetok w 12 miesiącu (zagojenia późne) od interwencji (I2) w grupach otrzymujących ASC (auto- i allogeniczne) w odniesieniu do grupy placebo.
3.Odsetek remisji (ustąpienie objawów czynnej przetoki) w 3 i 6 miesiącu od interwencji w grupach otrzymujących ASC (auto- i allogeniczne) w odniesieniu do grupy placebo.
4.Odsetek remisji (ustąpienie objawów czynnej przetoki) w 12 miesiącu od interwencji (I2) w grupach otrzymujących ASC (auto- i allogeniczne) w odniesieniu do grupy placebo.
5. Odsetek nawrotów w 12 miesiącu od interwencji w grupach otrzymujących ASC (auto- i allogeniczne) w odniesieniu do grupy placebo.

E.2.2

Secondary objectives of the trial

Safety evaluation of auto-ASC and allo-ASC in comparison to the placebo group.

Ocena profilu bezpieczeństwa auto-ASC, allo-ASC w odniesieniu do placebo.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Expressing informed consent to participate in the study and consent to the collection of adipose tissue.
2. Gender: female, male.
3. Age> 18 and <75 years of age.
4. Diagnosis of Crohn's disease.
5. Recto-cutaneous or rectovaginal fistula that persists despite at least 1 surgical intervention.
6. Stable picture of Crohn's disease *.
7. For women of childbearing potential, consent to use effective contraception throughout the study period or complete sexual abstinence (if this is the chosen lifestyle).

1. Wyrażenie świadomej zgody na udział w badaniu i wyrażenie zgody na pobranie tkanki tłuszczowej.
2. Płeć: kobieta, mężczyzna.
3. Wiek > 18 i <75 roku życia.
4. Rozpoznanie choroba Leśniowskiego i Crohna.
5. Przetoka skórno-odbytnicza lub odbytniczo-pochwowa utrzymująca się pomimo co najmniej 1 interwencji chirurgicznej.
6. Stabilny obraz chororby Leśniowskiego i Crohna*.
7. W przypadku kobiet w wieku rozrodczym, zgoda na stosowanie skutecznej antykoncepcji przez cały okres uczestnictwa badania lub całkowita wstrzemięźliwość seksualna (jeśli jest to wybrany styl życia).

E.4

Principal exclusion criteria

1. Lack of consent to participate in a clinical trial.
2. A fistula of a different etiology than Crohn's disease (eg discrete).
3. Coexisting mental disorders.
4. Limited contact making it impossible to understand and accept the test conditions,
5. Pregnancy, puerperium and breastfeeding
6. BMI <18 or no subcutaneous, abdominal fat,
7. HIV, HBV, HCV, HTLV, syphilis, or other infections that contraindicate living donation.
8. Infectious diseases involving the perineal region,
9. Active neoplastic disease or condition after treatment of malignant neoplasms (withdrawal period: 5 years from the end of treatment).
10. Immunosuppression within 4 weeks prior to screening visit.
11. Autoimmune diseases or infections (hepatitis B, hepatitis C, HIV, syphilis).
12. Failure of at least one organ (heart, liver, kidney, lung) with a statistically predicted life span <2 years,
13. Participation in any other clinical trial or therapeutic experiment (withdrawal period not shorter than 60 days).
14. Claustrophobia or other factors that prevent MRI,
15. Developmental disorders of the large intestine preventing rectoscopy,
16. Status after radiotherapy of the minor or major pelvis or the abdominal cavity.
17. Sensitization to the ingredients of the investigational medicinal product or gadolinium (MRI cannot be performed).

1. Brak zgody na udział w badaniu klinicznym.
2. Przetoka o etiologii innej niż choroba Leśniowskiego i Crohna (np. odkryptowa).
3. Współistniejące zaburzenia psychiczne.
4. Ograniczony kontakt uniemożliwiający zrozumienie i akceptacje warunków badania,
5. Ciąża, okres połogu i karmienia piersią
6. BMI < 18 lub brak podskórnej, brzusznej tkanki tłuszczowej,
7. Infekcje HIV, HBV, HCV, HTLV, kiła lub inne, które stanowią przeciwwskazania do donacji tkanki od żywego dawcy.
8. Choroby zakaźne obejmujące rejon krocza,
9. Aktywna choroba nowotworowa lub stan po leczeniu nowotworów złośliwych (okres karencji: 5 lat od zakończenia leczenia).
10. Immunosupresja w ciągu 4 tygodni przed wizytą przesiewową.
11. Choroby autoimmunologiczne lub infekcje (WZW-B, WZW-C, HIV, kiła).
12. Niewydolność co najmniej 1 narządu (serca, wątroby, nerek, płuc) o statystycznie przewidywanym czasie życia <2 lat,
13. Uczestnictwo w jakimkolwiek innym badaniu klinicznym lub eksperymencie leczniczym (okres karencji nie krócej niż 60 dni).
14. Klaustrofobia lub inne czynniki uniemożliwiające MRI,
15. Zaburzenia rozwojowe jelita grubego uniemożliwiające wykonanie rektoskopii,
16. Stan po radioterapii miednicy mniejszej lub większej lub jamy brzusznej.
17. Uczulenie na składniki badanego produktu leczniczego lub gadolin (brak możliwości wykonania MRI).

E.5 End points

E.5.1

Primary end point(s)

1. Percentage of healed fistulas at months 3 and 6 after intervention (I2) in the ASC groups (auto- and allogeneic) in relation to the placebo group.
2. Percentage of healed fistulas at month 12 (late healing) from intervention (I2) in the ASC groups (auto- and allogeneic) compared to the placebo group.
3. The rate of remission (resolution of active fistula symptoms) at months 3 and 6 after intervention (I2) in the ASC groups (auto- and allogeneic) compared to the placebo group.
4. Rate of remission (resolution of active fistula symptoms) at month 12 after intervention (I2) in the ASC groups (auto- and allogeneic) compared to the placebo group.
5. Relapse rate at month 12 after intervention (I2) in the ASC groups (auto- and allogeneic) compared to the placebo group.

1.Odsetek wygojonych przetok w 3 i 6 miesiącu od interwencji w grupach otrzymujących ASC (autologiczne i allogeniczne) w odniesieniu do grupy placebo.
2.Odsetek wygojonych przetok w 12 miesiącu (zagojenia późne) od interwencji (I2) w grupach otrzymujących ASC (auto- i allogeniczne) w odniesieniu do grupy placebo.
3.Odsetek remisji (ustąpienie objawów czynnej przetoki) w 3 i 6 miesiącu od interwencji w grupach otrzymujących ASC (auto- i allogeniczne) w odniesieniu do grupy placebo.
4.Odsetek remisji (ustąpienie objawów czynnej przetoki) w 12 miesiącu od interwencji (I2) w grupach otrzymujących ASC (auto- i allogeniczne) w odniesieniu do grupy placebo.
5. Odsetek nawrotów w 12 miesiącu od interwencji w grupach otrzymujących ASC (auto- i allogeniczne) w odniesieniu do grupy placebo.

E.5.1.1

Timepoint(s) of evaluation of this end point

3, 6 and 12 months from the date of the intervention

3, 6 i 12 miesięcy od dnia interwencji

E.5.2

Secondary end point(s)

The type and frequency of reactions and adverse events in the intervention groups in relation to the control group assessed during the study and at the last visit.

Rodzaj i częstość występowania reakcji i zdarzeń niepożądanych w grupach poddanych interwencji w odniesieniu do grupy kontrolnej oceniana w trakcie badania oraz na ostatniej wizycie.

E.5.2.1

Timepoint(s) of evaluation of this end point

3, 6 and 12 months from the date of the intervention

3, 6 i 12 miesięcy od dnia interwencji

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

240

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

240

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2024-12-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-12-14

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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IMP with orphan designation in the indication
Orphan Designation Number:
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