Study to Assess Efficacy and Safety of Cx601, Adult Allogeneic Expanded Adipose-derived Stem Cells (eASC) for the Treatment of Complex Perianal Fistula(s) in Participants With Crohn's Disease (CD)

Crohn's Disease Clinical Trial

— ADMIRE-CD-II  

Official title:

A Phase-III, Randomized, Double-blind, Parallel-group, Placebo-controlled, International, Multicentre Study to Assess Efficacy and Safety of Cx601, Adult Allogeneic Expanded Adipose-derived Stem Cells (eASC) for the Treatment of Complex Perianal Fistula(s) in Patients With Crohn's Disease Over a Period of 24 Weeks and a Follow-up Period up to 52 Weeks

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03279081
• Other study ID #: Cx601-0303
• Secondary ID: 2017-000725-12
• Status: Completed
• Phase: Phase 3
• Start date: September 15, 2017
• Est. completion date: July 26, 2023

Study information

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

Clinical Trial Summary

The purpose of this study is to evaluate the combined remission of complex perianal fistulas, defined as the clinical assessment at Week 24 of closure of all treated external openings that were draining at baseline despite gentle finger compression, and absence of collections greater than (>) 2 centimeter (cm) (in at least 2 dimensions) confirmed by blinded central magnetic resonance imaging (MRI) assessment at Week 24.

Description:

This study is to assess the efficacy and safety of Cx601, eASC, for the treatment of complex perianal fistulas in participants with Crohn's disease. The study will randomize approximately 554 participants. - Cx601 eASCs intralesional injection - Placebo - Cx601 placebo-matching eASCs intralesional injection Study treatments will be allocated, on a 1:1 ratio, by central randomization through interactive web response system (IWRS). The study will follow an add-on design, participants receiving any ongoing concomitant medical treatment, at stable doses at the time of screening, for the CD will be allowed to continue it throughout the study. The primary efficacy analysis, will be conducted at Week 24 timepoint. The double blind design will be maintained up to Week 52 (both participant and investigator) by a specific blinding for study treatment administration and for evaluating its efficacy. This multicenter trial will be conducted globally across 150 centers. The overall time to participate in this study is approximately 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 569
• Est. completion date: July 26, 2023
• Est. primary completion date: January 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Signed informed consent.

2. Participants of either gender greater than or equal to (>=) 18 years and less than or equal to (<=) 75 years of age.

3. Participants with CD diagnosed at least 6 months prior to Screening visit in accordance with accepted clinical, endoscopic, histological and/or radiological criteria.

4. Presence of complex perianal fistula(s) with a maximum of 2 internal openings and a maximum of 3 external openings based on clinical assessment; a central reading of a locally performed contrast enhanced (gadolinium) pelvic MRI will be performed to confirm location of the fistula and potential associated perianal abscess(es). Fistula(s) must have been draining for at least 6 weeks prior to Screening visit. Actively draining simple subcutaneous fistula(s), at the time of Screening visit, are not allowed in this study. A complex perianal fistula is defined as a fistula that

meets one or more of the following criteria :

• High inter-sphincteric, high trans-sphincteric, extra-sphincteric or suprasphincteric.
• Presence of >=2 external openings.
• Associated perianal abscess(es). Note: Abscesses that are larger than 2 cm at least 2 dimensions on MRI must be confirmed to have been drained adequately by the surgeon during the preparation curettage in order to be eligible.

5. Clinically controlled, nonactive or mildly active CD, during the last six months prior

to Screening visit with:

• A patient reported outcomes (PRO-2) score <14 at Screening, AND
• A colonoscopy documenting the absence of ulcers larger than 0.5 cm in the colonic

mucosa:

• If colonoscopy data are not available within 6 months prior to Screening:
• A simple endoscopic score for Crohn's Disease (SES-CD) <=6 with absence of rectal ulcers larger than 0.5 cm must be documented in a colonoscopy performed at Screening before randomization.
• If colonoscopy data are available within 6 months prior to Screening, the following must be documented, otherwise a new colonoscopy (as above) will be

mandatory:

• The absence of ulcers larger than 0.5 cm in the colonic mucosa AND
• the improvement or no worsening in abdominal pain and/or in the diarrhea, sustained for one week or more, since the last colonoscopy was performed in the clinical records until Screening visit. AND o No hemoglobin decrease >=2.0 gram per deciliter (g/dL) or an unexplained rising C-reactive protein (CRP), > 5.0 milligram per liter (mg/L) to a concentration above the referenced upper limit of normal (ULN) (unless the rise is due to a known process other than luminal Crohn's Disease), since the last colonoscopy was performed as compared to results during the Screening visit. AND o no initiation or intensification of treatment with corticosteroids, immunosuppressants or monoclonal antibodies (mAbs) dose regimen since the last endoscopy up to Screening visit.

6. Participants whose perianal fistulas were previously treated and have shown an inadequate response or a loss of response while they were receiving either an immunosuppressive agent or tumour necrosis factor (TNF)-alpha antagonist or vedolizumab or ustekinumab, or having documented intolerance to any of these treatments administered at least at approved or recommended doses during the minimum

period mentioned:

• Immunosuppressive agents: at least 3 months treatment with azathioprine (2-3 milligram per kilogram per day [mg/kg/day]), 6-mercaptopurine (1-1.5 mg/kg/day), or subcutaneous/intramuscular methotrexate (25 mg/week) prior to Screening for the study.
• TNFalpha antagonists:
• Infliximab: at least 14 weeks treatment at the approved doses for induction and/or maintenance in Crohn´s disease prior to screening for the study. For induction: 1 intravenous dose of 5 milligram per kilogram (mg/kg) followed by the same dose 2 and 6 weeks after. For maintenance: 5-10 mg/kg intravenously every 8 weeks, or more frequently.
• Adalimumab: at least 14 weeks treatment at the approved doses for induction and/or maintenance in Crohn's disease prior to screening for the study. For induction: 1 subcutaneous dose of 160 milligram (mg), followed by 80 mg 2 weeks after. For maintenance: 40 mg subcutaneously every other week, or weekly.
• Certolizumab l: at least 14 weeks treatment at the approved doses for induction and/or maintenance in Crohn´s disease prior to screening for the study. For induction: 1 subcutaneous dose of 400 mg, followed by the same dose 2 and 4 weeks after. For maintenance: 400 mg subcutaneously every 2 to 4 weeks.
• Anti-integrin: at least 14 weeks treatment of the approved dose for induction and/or maintenance in Crohn´s disease prior to screening for the study. For induction: Vedolizumab 300 mg. For maintenance: Vedolizumab 300 mg every 4 to 8 weeks.
• Anti-interleukin (IL)-12/23: at least 16 weeks treatment of the approved dose in Crohn´s disease prior to screening for the study. For induction: Ustekinumab, approximately 6mg/kg intravenously initially then followed by 90 mg subcutaneously every 8 weeks.

7. Women of childbearing potential (WCBP) must have negative serum pregnancy test at screening (sensitive to 25 international units [IU] human chorionic gonadotropin [hCG]). Both WCBP or male participants participating in this study, with a WCBP as partner, must agree to use an adequate method of contraception during the entire duration of the study. An adequate method of contraception is defined as complete, non-periodic sexual abstinence (refraining from heterosexual intercourse), single-barrier method, vasectomy, adequate hormonal contraception (to have started at least 7 days prior to Screening visit), or an intra-uterine device (to have been in place for at least 2 months prior to Screening visit).

Exclusion Criteria:

1. Concomitant rectovaginal or rectovesical fistula(s).

2. Participant naïve to prior specific medical treatment for complex perianal fistula(s) including immunosuppressant (IS) or anti-TNFs.

3. Presence of a perianal collection >2 cm in at least two dimensions on the central reading MRI at Screening visit that was not adequately drained as confirmed by the surgeon during the preparation procedure (week -3 to day 0).

4. Severe rectal and/or anal stenosis and/or severe proctitis (defined as the presence of large >0.5 cm ulcers in the rectum) that make impossible to follow the surgery procedure manual.

5. Participant with diverting stomas.

6. Active, uncontrolled infection requiring parenteral antibiotics.

7. Participant with ongoing systemic or rectal steroids for CD in the last 2 weeks prior to the Preparation visit.

8. Participants with major alteration on any of the following laboratory tests or

increased risk for the surgical procedure:

• Serum creatinine levels >1.5 times the ULN
• Total bilirubin >1.5 ULN
• Aspartate Transaminase (AST)/ Alanine Transaminase (ALT) >3 times ULN
• Hemoglobin <10.0 g/dL
• Platelets <75.0*10^9/L
• Albuminemia <3.0 g/dL

9. Suspected or documented infectious enterocolitis within two weeks prior to Screening visit.

10. Any prior invasive malignancy diagnosed within the last 5 years prior to Screening visit. Participants with basal-cell carcinoma of the skin completely resected outside the perineal region can be included.

11. Current or recent (within 6 months prior to the Screening visit) history of severe, progressive, and/or uncontrolled hepatic, haematological, gastrointestinal (GI) (other than CD), renal, endocrine, pulmonary, cardiac, neurological or psychiatric disease that may result in participants increased risk from study participation and/or lack of compliance with study procedures.

12. Participants with primary sclerosing cholangitis.

13. Participants with known chronically active hepatopathy of any origin, including cirrhosis and participants with persistent positive Hepatitis B Virus (HBV) surface antigen (HBsAg) and quantitative HBV polymerase chain reaction (PCR), or positive serology for Hepatitis C Virus (HCV) and quantitative HCV PCR within 6 months prior to Screening.

14. Congenital or acquired immunodeficiencies, including participants known to be HIV carriers

15. Known allergies or hypersensitivity to penicillin or aminoglycosides; Dulbecco Modified Eagle's Medium (DMEM); bovine serum; local anaesthetics or gadolinium (MRI contrast).

16. Contraindication to MRI scan (example, due to the presence of pacemakers, hip replacements or severe claustrophobia).

17. Severe trauma within 6 months prior to Screening visit.

18. Pregnant or breastfeeding women.

19. Participants who do not wish to or cannot comply with study procedures.

20. Participants currently receiving, or having received any investigational drug within 3 months prior to Screening visit.

21. Participants previously treated with Cx601 or other allogeneic stem-cell therapy cannot be enrolled into this clinical study.

22. Any major surgery of the GI tract (including one or more segments of the colon or terminal ileum) within 6 months prior the screening or any minor surgery of the GI tract within 3 months prior to screening.

23. Participants who had local perianal surgery other than drainage for the fistula within 6 months prior to the Screening visit, or those who may need surgery in the perianal region for reasons other than fistulas at the time of inclusion in the study.

24. Contraindication to the anaesthetic procedure.

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease
• Fistula

Intervention

Drug:
• Cx601
Cx601 eASCs intralesional injection.

Other:
• Placebo
Cx601 placebo-matching eASCs intralesional injection.

Locations

Country	Name	City	State
Belgium	GZA ziekenhuizen - Campus Sint-Vincentius - Gastro-enterology	Antwerpen
Belgium	Imelda Ziekenhuis	Antwerpen
Belgium	UZ Gent - Gastroenterology	Gent
Belgium	AZ Groeninge - Campus Kennedylaan - Gastro-enterology	Kortrijk	West-Vlaanderen
Belgium	UZ Leuven - Campus Gasthuisberg	Leuven	Vlaams Brabant
Belgium	CHU de Liege - Domaine Universitaire du Sart Tilman	Liege
Belgium	Clinique Saint-Joseph (CHC)	Liege
Belgium	CHU Dinant Godinne UCL Namur	Namur
Belgium	AZ Delta vzw - Maag-darm-leverziekten	Roeselare	West-Vlaanderen
Canada	University of Alberta	Edmonton	Alberta
Canada	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	McGill University Health Centre - Montreal General Hospital	Montreal	Quebec
Canada	Ottawa Hospital	Ottawa	Ontario
Canada	Kensington Screening Clinic - Gastroenterology	Toronto	Ontario
Canada	Mount Sinai Hospital - Toronto - Gastroenterology	Toronto	Ontario
Canada	(G.I.R.I.) GI Research Institute	Vancouver	British Columbia
Czechia	NH Hospital a.s.	Horovice	Beroun
Czechia	FN Hradec Kralove	Hradec Kralove
Denmark	Aarhus University Hospital - Department of Hepatology and Gastroenterology, Lever-Mave- og Tarmsygdomme Klinik, krydspunkt C216	Aarhus
Denmark	Bispebjerg Hospital	Kobenhavn	Copenhague
Denmark	Odense Universitetshospital	Odense
France	CHU Amiens-Picardie	AMIENS cedex 1	Picardie
France	CHU de Clermont-Ferrand - Estaing	Clermont-Ferrand cedex 1	Auvergne
France	Hopital Beaujon	Clichy	Ile-de-France
France	CHRU De Lille - Hopital Claude Huriez - Hepato-Gastro-Enterologie	Lille	Nord
France	CHU de Nice	Nice Cedex 03	Alpes-Maritimes
France	Hopital Saint Louis - Gastro-hepatoenterologie	Paris	Ile-de-France
France	Paris St. Joseph Hospital	Paris
France	Centre Hospitalier Lyon Sud	Pierre-Benite	Rhone
France	CHRU Hopital De Pontchaillou	Rennes	Ille-et-Vilaine
France	CHU Saint Etienne	St Priest en Jarez	Loire
France	Centre Hospitalier Universitaire De Toulouse - Hopital De Ra	Toulouse cedex 09	Haute-Garonne
France	CHRU de Nancy -Hopital Brabois Adultes - Service d'Hepato- Gastroenterologie	Vandoeuvre-les-Nancy	Lorraine
Germany	Universitatsklinikum Dresden	Dresden	Sachsen
Germany	Universitatsklinikum Erlangen	Erlangen	Bayern
Germany	Klinikum der Johann Wolfgang Goethe-Universitat	Frankfurt/Main	Hessen
Germany	Klinikum der Universitat Munchen - Campus Grosshadern	Munchen	Bayern
Hungary	MH Egeszsegugyi Kozpont - Gasztroenterologiai Osztaly	Budapest	Pest
Hungary	Semmelweis Egyetem	Budapest	Pest
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen	Hajdu-Bihar
Hungary	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont - I. sz. Belgyogyaszati Klinika	Szeged	Csongrad
Israel	Rambam Medical Centre	Haifa	HaZafon
Israel	Hadassah Medical Organization, Hadassah Medical Center, Ein-	Jerusalem	Yerushalayim
Israel	Shaare Zedek Medical Center - Gastroenterology	Jerusalem	Yerushalayim
Israel	Rabin Med Ctr Beilinson Hosp	Petah Tikva	HaMerkaz
Israel	Chaim sheba Medical Center	Tel Hashomer	Tel-Aviv
Italy	Policlinico S. Orsola Malpighi, AOU di Bologna-U.O. di Medicina Interna.	Bologna
Italy	Ospedale Santissima Annunziata	Cento	Ferrara
Italy	AOU Policlinico di Modena - Gastroenterologia	Modena
Italy	II Universita degli Studi di Napoli	Napoli
Italy	Gastroenterology Section	Palermo
Italy	Universita degli studi di Pisa	Pisa
Italy	A.O. San Camillo Forlanini	Roma
Italy	Complesso Integrato Columbus	Roma
Italy	Policlinico Universitario Agostino Gemelli	Roma
Italy	Policlinico Universitario Campus Biomedico - UOC di Gastroenterologia	Roma
Italy	Istituto Clinico Humanitas Rozzano, IRCCS - IBD Center	Rozzano	Milano
Italy	Azienda Ospedaliero Universitaria S.Maria della Misericordia - Gastroenterologia	Udine
Italy	Azienda Ospedaliera Universitaria Integrata Verona (AOUI) -	Verona
Poland	COPERNICUS Podmiot Leczniczy Sp. z o.o.	Gdansk
Poland	Centrum Medyczne PROMED	Krakow	Malopolskie
Poland	Uniwersytecki Szpital Kliniczny im. Wojskowej Akademii Medycznej Centralny Szpital Weteranow	Lodz	Lodzkie
Poland	Endoskopia Sp z o.o.	Sopot	Pomorskie
Poland	Centralny Szpital Kliniczny MSWiA w Warszawie	Warszawa
Poland	Wielospecjalistyczny Szpital Medicover	Warszawa	Mazowieckie
Poland	Centrum Medyczne Melita Medical	Wroclaw	Dolnoslaskie
Puerto Rico	University of Puerto Rico School of Medicine	San Juan
Spain	H.U. G.Trias i Pujol	Badalona	Barcelona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario de Fuenlabrada	Fuenlabrada	Madrid
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid
Spain	Hospital Universitario Son Espases	Palma de Mallorca	Baleares
Spain	C.H.U. de Pontevedra	Pontevedra
Spain	Corporacio Sanitaria Parc Tauli	Sabadell	Barcelona
Spain	Hospital de Sagunto	Sagunto	Valencia
Spain	H.U.V. del Rocio	Sevilla
Sweden	Linkoping University Hospital - Department of Surgery	Linkoping	Ostergotlands Lan [se-05]
United Kingdom	Addenbrooke's Hospital	Cambridge	Cambridgeshire
United Kingdom	NHS Greater Glasgow and Clyde - Glasgow Royal Infirmary (GRI)	Glasgow	Glasgow City
United Kingdom	St. Mark's Hospital	Harrow	London, City Of
United Kingdom	Guys & St Thomas	London	London, City Of
United Kingdom	University Colleague London Hospital (UCLH)	London
United Kingdom	Wythenshawe Hospital - Gastroenterology	Manchester
United Kingdom	Nottingham University Hospitals NHS Trust - Surgery	Nottingham	Nottinghamshire
United Kingdom	Northern General Hospital	Sheffield
United States	Albany Medical Center	Albany	New York
United States	Emory University	Atlanta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	Johns Hopkins Medicine - The Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	Digestive Health Center of Louisiana	Baton Rouge	Louisiana
United States	Boston Medical Center	Boston	Massachusetts
United States	Massachussetts General Hospital	Boston	Massachusetts
United States	Lahey Hospital & Medical Center	Burlington	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	The University of Chicago Medicine - Colon & Rectal Surgery	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	UT Southwestern Medical Center - Gastroenterology - Gastroenterology	Dallas	Texas
United States	Hartford Hospital - Gastroenterology	Farmington	Connecticut
United States	Harvard Medical School-Beth Israel Deaconess Medical Center	Hershey	Pennsylvania
United States	Penn State Hershey Medical Center - Surgery	Hershey	Pennsylvania
United States	Baylor College of Medicine (BCM) - Gastroenterology	Houston	Texas
United States	Indiana University - Colon and Rectal	Indianapolis	Indiana
United States	Mayo Clinic - Gastroenterology	Jacksonville	Florida
United States	University of Kansas Sxchool of Medicine	Kansas City	Kansas
United States	UC San Diego Health Systems	La Jolla	California
United States	University of Nevada School of Medicine	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center - Cancer Center	Lebanon	New Hampshire
United States	University of Southern California (USC) Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	North Shore University Hospital - Gastroenterology	Manhasset	New York
United States	Colon and Rectal Surgery Associates	Metairie	Louisiana
United States	University of Miami Hospital	Miami	Florida
United States	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin Hub for Collaborative Medicine - Gastroenterology and Hepatology	Milwaukee	Wisconsin
United States	Morristown Medical Center - Gastroenterology	Morristown	New Jersey
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	University Medical Center - New Orleans	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Lenox Hill Hospital	New York	New York
United States	NYU Langone Medical Center	New York	New York
United States	Stony Brook University Medical Center	New York	New York
United States	Weill Medical College of Cornell University	New York	New York
United States	UC Irvine Medical Center - Chao Family Comprehensive Cancer	Orange	California
United States	Florida Hospital Orlando	Orlando	Florida
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	OHSU Digestive Health Center	Portland	Oregon
United States	University Surgical Associates-Rhode Island Hospital	Providence	Rhode Island
United States	Rapid City Medical Center	Rapid City	South Dakota
United States	Inland Empire Liver Foundation	Rialto	California
United States	Carilion Clinic	Roanoke	Virginia
United States	Mayo Clinic College of Medicine - Division of Colon and Rectal Surgery - Division of Colon and Rectal Surgery	Rochester	Minnesota
United States	Barnes-Jewish Hospital - Gastroenterology	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	Kaiser Permamente	San Francisco	California
United States	University of California San Francisco	San Francisco	California
United States	Scottsdale Mayo Clinic	Scottsdale	Arizona
United States	Swedish Medical Center	Seattle	Washington
United States	Virginia Mason Medical Center - Gastroenterology	Seattle	Washington
United States	Florida Hospital Tampa	Tampa	Florida
United States	USF Health South Tampa Center for Advanced Healthcare	Tampa	Florida
United States	Carle Foundation Hospital	Urbana	Illinois
United States	Vallejo Hospital and Medical Offices	Vallejo	California
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Cedar-Sinai Medical Center	West Hollywood	California
United States	Cleveland Clinic Florida	Weston	Florida
United States	University of Massachusetts - colon & rectal surgery	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Tigenix S.A.U.

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czechia,  Denmark,  France,  Germany,  Hungary,  Israel,  Italy,  Poland,  Puerto Rico,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Combined Remission at Week 24	Combined Remission is defined as the closure of all treated external openings that were draining at baseline despite gentle finger compression and absence of collection(s) >2 cm (in at least 2 dimensions) of the treated perianal fistula(s) confirmed by blinded central MRI assessment.	Week 24
Secondary	Percentage of Participants with Clinical Remission at Week 24	Clinical remission is defined as closure of all treated external openings that were draining at baseline despite gentle finger compression.	Week 24
Secondary	Time to Clinical Remission up to Week 24	Time to clinical remission is defined as the time from treatment start to first visit with closure of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed.	From the treatment start to first visit with closure of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed (up to Week 24)
Secondary	Percentage of Participants with Clinical Response at Week 24	Clinical response is defined as closure of at least 50 percent (%) of all treated external openings that were draining at baseline despite gentle finger compression.	Week 24
Secondary	Time to Clinical Response up to Week 24	Time to clinical response is defined as the time from treatment start to first visit with closure of at least 50% of all treated external openings that were draining at baseline, despite gentle finger compression, as clinically assessed.	From treatment start to first visit with closure of at least 50% of all treated external openings that were draining at baseline, despite gentle finger compression, as clinically assessed (up to Week 24)
Secondary	Percentage of Participants with Combined Remission at Week 52	Combined Remission is defined as the closure of all treated external openings that were draining at baseline despite gentle finger compression, and absence of collections >2 cm (in at least 2 dimensions) confirmed by blinded central MRI assessment.	Week 52
Secondary	Percentage of Participants with Clinical Remission at Week 52	Clinical remission is defined as closure of all treated external openings that were draining at baseline despite gentle finger compression.	Week 52
Secondary	Percentage of Participants with Clinical Response at Week 52	Clinical response is defined as closure of at least 50% of all treated external openings that were draining at baseline, despite gentle finger compression.	Week 52
Secondary	Time to Clinical Remission up to Week 52	Time to clinical remission is defined as the time from treatment start to first visit with closure of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed.	From treatment start to first visit with closure of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed (up to Week 52)
Secondary	Time to Clinical Response up to Week 52	Time to clinical response is defined as time from treatment start to first visit with closure of at least 50% of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed.	From treatment start to first visit with closure of at least 50% of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed (up to Week 52)
Secondary	Percentage of Participants with Relapse from Week 24 Combined Remission	Relapse is defined as reopening of any of the treated fistulas external openings with active drainage as clinically assessed, or the development of a perianal fluid collection >2 cm of the treated perianal fistula confirmed by centrally read MRI assessment in participants who were in combined remission at week 24.	Week 24
Secondary	Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs)		Week 24 and Week 52
Secondary	Number of Participants With TEAEs Related to Vital Sign Parameters		Week 24 and Week 52
Secondary	Number of Participants With TEAEs Related to Clinical Laboratory Parameters		Week 24 and Week 52