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) (ADMIRE-CD-II)
Crohn's Disease
About this trial
This is an interventional treatment trial for Crohn's Disease focused on measuring Crohn's disease, complex perianal fistula(s)
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent.
- Participants of either gender greater than or equal to (>=) 18 years and less than or equal to (<=) 75 years of age.
- Participants with CD diagnosed at least 6 months prior to Screening visit in accordance with accepted clinical, endoscopic, histological and/or radiological criteria.
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.
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.
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.
- 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:
- Concomitant rectovaginal or rectovesical fistula(s).
- Participant naïve to prior specific medical treatment for complex perianal fistula(s) including immunosuppressant (IS) or anti-TNFs.
- 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).
- 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.
- Participant with diverting stomas.
- Active, uncontrolled infection requiring parenteral antibiotics.
- Participant with ongoing systemic or rectal steroids for CD in the last 2 weeks prior to the Preparation visit.
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
- Suspected or documented infectious enterocolitis within two weeks prior to Screening visit.
- 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.
- 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.
- Participants with primary sclerosing cholangitis.
- 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.
- Congenital or acquired immunodeficiencies, including participants known to be HIV carriers
- Known allergies or hypersensitivity to penicillin or aminoglycosides; Dulbecco Modified Eagle's Medium (DMEM); bovine serum; local anaesthetics or gadolinium (MRI contrast).
- Contraindication to MRI scan (example, due to the presence of pacemakers, hip replacements or severe claustrophobia).
- Severe trauma within 6 months prior to Screening visit.
- Pregnant or breastfeeding women.
- Participants who do not wish to or cannot comply with study procedures.
- Participants currently receiving, or having received any investigational drug within 3 months prior to Screening visit.
- Participants previously treated with Cx601 or other allogeneic stem-cell therapy cannot be enrolled into this clinical study.
- 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.
- 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.
- Contraindication to the anaesthetic procedure.
Sites / Locations
- Scottsdale Mayo Clinic
- UC San Diego Health Systems
- University of Southern California (USC) Norris Comprehensive Cancer Center
- UC Irvine Medical Center - Chao Family Comprehensive Cancer
- Inland Empire Liver Foundation
- Kaiser Permamente
- University of California San Francisco
- Vallejo Hospital and Medical Offices
- Cedar-Sinai Medical Center
- University of Colorado Hospital
- Hartford Hospital - Gastroenterology
- Yale University School of Medicine
- MedStar Georgetown University Hospital
- Mayo Clinic - Gastroenterology
- University of Miami Hospital
- Florida Hospital Orlando
- USF Health South Tampa Center for Advanced Healthcare
- Florida Hospital Tampa
- Cleveland Clinic Florida
- Emory University
- Northwestern University
- Rush University Medical Center
- The University of Chicago Medicine - Colon & Rectal Surgery
- Carle Foundation Hospital
- Indiana University - Colon and Rectal
- University of Kansas Sxchool of Medicine
- University of Louisville
- Digestive Health Center of Louisiana
- Colon and Rectal Surgery Associates
- University Medical Center - New Orleans
- University of Maryland
- Johns Hopkins Medicine - The Johns Hopkins Hospital
- Massachussetts General Hospital
- Boston Medical Center
- Lahey Hospital & Medical Center
- University of Massachusetts - colon & rectal surgery
- Mayo Clinic College of Medicine - Division of Colon and Rectal Surgery - Division of Colon and Rectal Surgery
- Barnes-Jewish Hospital - Gastroenterology
- University of Nevada School of Medicine
- Dartmouth Hitchcock Medical Center - Cancer Center
- Morristown Medical Center - Gastroenterology
- Albany Medical Center
- North Shore University Hospital - Gastroenterology
- NYU Langone Medical Center
- Stony Brook University Medical Center
- Weill Medical College of Cornell University
- Icahn School of Medicine at Mount Sinai
- Columbia University Medical Center
- Lenox Hill Hospital
- Cleveland Clinic
- OHSU Digestive Health Center
- Harvard Medical School-Beth Israel Deaconess Medical Center
- Penn State Hershey Medical Center - Surgery
- Thomas Jefferson University Hospital
- Allegheny General Hospital
- University Surgical Associates-Rhode Island Hospital
- Medical University of South Carolina
- Rapid City Medical Center
- Vanderbilt University Medical Center
- UT Southwestern Medical Center - Gastroenterology - Gastroenterology
- Baylor College of Medicine (BCM) - Gastroenterology
- University of Utah
- University of Virginia
- Carilion Clinic
- Virginia Mason Medical Center - Gastroenterology
- Swedish Medical Center
- Aurora St. Luke's Medical Center
- Medical College of Wisconsin Hub for Collaborative Medicine - Gastroenterology and Hepatology
- UZ Leuven - Campus Gasthuisberg
- AZ Groeninge - Campus Kennedylaan - Gastro-enterology
- AZ Delta vzw - Maag-darm-leverziekten
- GZA ziekenhuizen - Campus Sint-Vincentius - Gastro-enterology
- Imelda Ziekenhuis
- UZ Gent - Gastroenterology
- CHU de Liege - Domaine Universitaire du Sart Tilman
- Clinique Saint-Joseph (CHC)
- CHU Dinant Godinne UCL Namur
- University of Alberta
- (G.I.R.I.) GI Research Institute
- Ottawa Hospital
- Mount Sinai Hospital - Toronto - Gastroenterology
- Kensington Screening Clinic - Gastroenterology
- Centre Hospitalier de l'Universite de Montreal
- McGill University Health Centre - Montreal General Hospital
- NH Hospital a.s.
- FN Hradec Kralove
- Bispebjerg Hospital
- Aarhus University Hospital - Department of Hepatology and Gastroenterology, Lever-Mave- og Tarmsygdomme Klinik, krydspunkt C216
- Odense Universitetshospital
- CHU de Nice
- CHU de Clermont-Ferrand - Estaing
- Centre Hospitalier Universitaire De Toulouse - Hopital De Ra
- Hopital Beaujon
- Hopital Saint Louis - Gastro-hepatoenterologie
- CHRU Hopital De Pontchaillou
- CHU Saint Etienne
- CHRU de Nancy -Hopital Brabois Adultes - Service d'Hepato- Gastroenterologie
- CHRU De Lille - Hopital Claude Huriez - Hepato-Gastro-Enterologie
- CHU Amiens-Picardie
- Centre Hospitalier Lyon Sud
- Paris St. Joseph Hospital
- Universitatsklinikum Erlangen
- Klinikum der Universitat Munchen - Campus Grosshadern
- Klinikum der Johann Wolfgang Goethe-Universitat
- Universitatsklinikum Dresden
- Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont - I. sz. Belgyogyaszati Klinika
- Debreceni Egyetem Klinikai Kozpont
- MH Egeszsegugyi Kozpont - Gasztroenterologiai Osztaly
- Semmelweis Egyetem
- Rabin Med Ctr Beilinson Hosp
- Rambam Medical Centre
- Chaim sheba Medical Center
- Shaare Zedek Medical Center - Gastroenterology
- Hadassah Medical Organization, Hadassah Medical Center, Ein-
- Ospedale Santissima Annunziata
- Istituto Clinico Humanitas Rozzano, IRCCS - IBD Center
- Policlinico S. Orsola Malpighi, AOU di Bologna-U.O. di Medicina Interna.
- AOU Policlinico di Modena - Gastroenterologia
- II Universita degli Studi di Napoli
- Gastroenterology Section
- Universita degli studi di Pisa
- Policlinico Universitario Campus Biomedico - UOC di Gastroenterologia
- A.O. San Camillo Forlanini
- Complesso Integrato Columbus
- Policlinico Universitario Agostino Gemelli
- Azienda Ospedaliero Universitaria S.Maria della Misericordia - Gastroenterologia
- Azienda Ospedaliera Universitaria Integrata Verona (AOUI) -
- Centrum Medyczne Melita Medical
- Uniwersytecki Szpital Kliniczny im. Wojskowej Akademii Medycznej Centralny Szpital Weteranow
- Centrum Medyczne PROMED
- Wielospecjalistyczny Szpital Medicover
- Endoskopia Sp z o.o.
- COPERNICUS Podmiot Leczniczy Sp. z o.o.
- Centralny Szpital Kliniczny MSWiA w Warszawie
- University of Puerto Rico School of Medicine
- Hospital Universitario Son Espases
- H.U. G.Trias i Pujol
- Corporacio Sanitaria Parc Tauli
- Hospital Universitario de Fuenlabrada
- Hospital Universitario Puerta de Hierro Majadahonda
- Hospital de Sagunto
- Hospital Clinic de Barcelona
- Hospital del Mar
- Hospital Universitario Ramon y Cajal
- Hospital Clinico San Carlos
- Hospital Universitario Fundacion Jimenez Diaz
- Hospital Universitario 12 de Octubre
- Hospital Universitario La Paz
- C.H.U. de Pontevedra
- H.U.V. del Rocio
- Linkoping University Hospital - Department of Surgery
- Addenbrooke's Hospital
- NHS Greater Glasgow and Clyde - Glasgow Royal Infirmary (GRI)
- St. Mark's Hospital
- Guys & St Thomas
- Nottingham University Hospitals NHS Trust - Surgery
- University Colleague London Hospital (UCLH)
- Wythenshawe Hospital - Gastroenterology
- Northern General Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Cx601
Placebo
Cx601 eASCs 120 million cells (5 million cells per milliliter [mL]) will be administered once by intralesional injection.
CX601 placebo-matching eASCs cells will be administered once by intralesional administration.