- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04701411
A Study of Darvadstrocel for Treating Complex Perianal Fistulas in Children and Teenagers With Crohn's Disease
A Phase 3, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of Darvadstrocel in the Treatment of Complex Perianal Fistula in Pediatric Subjects With Crohn's Disease Over a Period of 24 Weeks and an Extended Follow-up Period for a Total of up to 52 Weeks
A perianal fistula is an abnormal passageway that develops between the rectum and the skin near the anus. The fistula is considered complex if it branches into several openings or an abscess is also present.
The main aim of this study is to learn if complex perianal fistulas in children and teenagers close after treatment with darvadstrocel.
2 to 3 weeks before treatment with darvadstrocel, each participant will have surgery to clean the fistula and to drain any abscesses. On the day of treatment, each participant will have the fistula cleaned and will receive an injection of darvadstrocel near the fistula, under anesthetic.
For up to 1 year after treatment, participants will regularly visit the clinic for follow-up. The fistula will be examined and any side effects from the treatment will be recorded. Participants will have an MRI at one clinic visit (about 24 weeks after treatment).
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The drug being tested in this study is called darvadstrocel (Cx601, cell suspension containing 120 million cells of allogeneic expanded adipose-derived mesenchymal stem cells [eASCs]). Darvadstrocel is being tested to treat complex perianal fistula in pediatric participants who have Crohn's disease (CD). This study will look at the safety and efficacy of darvadstrocel in the treatment of complex perianal fistula in CD.
The study will enroll at least 20 patients who will receive a single dose of darvadstrocel.
This multi-center trial will be conducted worldwide. The overall time to participate in this study is 52 weeks.
Participants will make multiple visits to the clinic. In unavoidable circumstances, such as the coronavirus disease 2019 pandemic, exceptions may be granted for alternative methods for conducting participant visits with approval by the medical monitor and/or sponsor.
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Takeda Study Registration Call Center
- Phone Number: +1-877-825-3327
- Email: medinfoUS@takeda.com
Study Locations
-
-
-
Be'er Ya'aqov, Israel, 7033001
- Recruiting
- Shamir Medical Center (Assaf Harofeh)
-
Contact:
- Site Contact
- Phone Number: 972897797202
- Email: efratb@asaf.health.gov.il
-
Principal Investigator:
- EFRAT BROIDE
-
Haifa, Israel, 3109601
- Recruiting
- Rambam Health Care Campus
-
Principal Investigator:
- Ron Shaoul
-
Contact:
- Site Contact
- Phone Number: 97248542914
- Email: r_shaoul@rambam.health.gov.il
-
Jerusalem, Israel, 91031
- Recruiting
- Shaare Zedek Medical Center
-
Principal Investigator:
- Dan Turner
-
Contact:
- Site Contact
- Phone Number: 97226666482
- Email: turnerd@szmc.org.il
-
Jerusalem, Israel, 9124001
- Recruiting
- Hadassah University Hospital-Mt. Scopus
-
Principal Investigator:
- Zev Davidovics
-
Contact:
- Site Contact
- Phone Number: 972586645719
- Email: zevd@hadassah.org.il
-
Petach-Tikva, Israel, 4920235
- Recruiting
- Schneider Children's Medical Center
-
Principal Investigator:
- Raanan Shamir
-
Contact:
- Site Contact
- Phone Number: 972309253672
- Email: shamirraanan@gmail.com
-
-
-
-
-
Bunkyo-ku, Japan, 113-8431
- Recruiting
- Juntendo University Hospital
-
Principal Investigator:
- Takahiro Kudo
-
Contact:
- Site Contact
- Phone Number: 81338133111
- Email: t-kudo@juntendo.ac.jp
-
Bunkyo-ku, Japan, 113-8519
- Recruiting
- Medical Hospital, Tokyo Medical and Dental University
-
Principal Investigator:
- Masakazu Nagahori
-
Contact:
- Site Contact
- Phone Number: 81338136111
- Email: nagahori.gast@tmd.ac.jp
-
Sendai-shi, Japan, 989-3126
- Recruiting
- Miyagi Children's Hospital
-
Contact:
- Site Contact
- Phone Number: 81223915111
- Email: lastnamefirstname@email.jp
-
Principal Investigator:
- Daiki Abukawa
-
Shimotsuke-shi, Japan, 329-0498
- Recruiting
- Jichi Medical University Hospital
-
Contact:
- Site Contact
- Phone Number: 81285442111
- Email: lastnamefirstname@email.jp
-
Principal Investigator:
- Hideki Kumagai
-
Tsu-shi, Japan, 514-8507
- Recruiting
- Mie University Hospital
-
Contact:
- Site Contact
- Phone Number: 81592321111
- Email: ucchie@clin.medic.mie-u.ac.jp
-
Principal Investigator:
- Keiichi Uchida
-
-
-
-
-
Amsterdam, Netherlands, 1105 AZ
- Recruiting
- Amsterdam UMC, Locatie AMC
-
Contact:
- Site Contact
- Phone Number: 31205669111
- Email: j.e.vanlimbergen@amsterdamumc.nl
-
Principal Investigator:
- Johan Van Limbergen
-
Groningen, Netherlands, 9713 GZ
- Recruiting
- Universitair Medisch Centrum Groningen (Umcg)
-
Contact:
- Site Contact
- Phone Number: 31503614717
- Email: p.f.van.rheenen@umcg.nl
-
Principal Investigator:
- Patrick van Rheenen
-
Rotterdam, Netherlands, 3000 CA
- Recruiting
- Erasmus Medisch Centrum
-
Contact:
- Site Contact
- Phone Number: 31107036049
- Email: l.deridder@erasmusmc.nl
-
Principal Investigator:
- Lissy De Ridder
-
-
-
-
-
Krakow, Poland, 30-663
- Recruiting
- Uniwersytecki Szpital Dzieciecy w Krakowie
-
Contact:
- Site Contact
- Phone Number: 481265820111440
- Email: misladek@cyf-kr.edu.pl
-
Principal Investigator:
- Malgorzata Sladek
-
Rzeszow, Poland, 35-302
- Recruiting
- Gabinet Lekarski Bartosz Korczowski
-
Principal Investigator:
- Bartosz Korczowski
-
Contact:
- Site Contact
- Phone Number: 48604481752
- Email: korczowski@op.pl
-
Warszawa, Poland, 04-730
- Recruiting
- Instytut "Pomnik - Centrum Zdrowia Dziecka"
-
Principal Investigator:
- Jaroslaw Kierkus
-
Contact:
- Site Contact
- Phone Number: 48500111648
- Email: j.kierkus@wip.waw.pl
-
-
-
-
-
Badalona, Spain, 8916
- Recruiting
- Hospital Universitari Germans Trias I Pujol
-
Contact:
- Site Contact
- Phone Number: 34676588434
- Email: moviedo.germanstrias@gencat.cat
-
Principal Investigator:
- Maria Oviedo Gutierrez
-
Barcelona, Spain, 8035
- Recruiting
- Hospital Universitari Vall d'Hebron
-
Contact:
- Site Contact
- Phone Number: 34932746213
- Email: osegarra@vhebron.net
-
Principal Investigator:
- Oscar Segarra Canton
-
Barcelona, Spain, 8950
- Recruiting
- Hospital Sant Joan de Deu
-
Contact:
- Site Contact
- Phone Number: 34932532100
- Email: javiermartin@sjdhospitalbarcelona.org
-
Principal Investigator:
- Francisco Javier Martin Carpi
-
Madrid, Spain, 28009
- Recruiting
- Hospital Infantil Universitario Nino Jesus
-
Contact:
- Site Contact
- Phone Number: 34680484490
- Email: jlorenzo.alonso@salud.madrid.org
-
Principal Investigator:
- Jose Lorenzo Alonso Calderon
-
Madrid, Spain, 28040
- Recruiting
- Hospital Universitario Fundacion Jimenez Diaz
-
Contact:
- Site Contact
- Phone Number: 34915504800
- Email: maria.mibeas@quironsalud.es
-
Principal Investigator:
- Maria de los Angeles Martinez Ibeas
-
Malaga, Spain, 29011
- Recruiting
- Hospital Materno-Infantil de Malaga
-
Contact:
- Site Contact
- Phone Number: +34951292191 X2374
- Email: victor.navas@gmail.com; victorm.navas.sspa@juntadeandalucia.es
-
Principal Investigator:
- Victor Manuel Navas Lopez
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Has a CD diagnosis based on accepted clinical, endoscopic, histological and/or radiologic criteria at least 6 months before the screening visit.
- Has complex perianal fistula refractory to at least one of the following treatments: immunosuppressants or biologics (anti-TNFs, anti-integrin, anti-interleukin [IL] 12/23). Fistula(s) refractory to therapy is defined in this study as follows: Immunosuppressants: Inadequate response after 3 months, based on clinical assessment, or more treatment with azathioprine, 6-mercaptopurine or methotrexate. Biologics: Inadequate response after 14 weeks (16 weeks for anti-IL 12/23), based on clinical assessment, or more standard treatment for induction and maintenance.
A complex perianal fistula(s) that meets one or more of the following criteria, modified from the American Gastroenterological Association (AGA) technical review: High intersphincteric, transsphincteric, extrasphincteric, or suprasphincteric as assessed by MRI. Presence of 2 or 3 external openings (tracts) as assessed by clinical examination. Associated fluid (abscess) collections as determined by MRI.
This study requires that the participant has complex perianal fistulas with a maximum of 2 internal openings and a maximum of 3 external openings, based on clinical assessment. Darvadstrocel treatment is targeted for fistulas that connect between internal and external openings. A central reading of a locally performed pelvic MRI will be performed to confirm the location of the fistula and potential associated perianal abscess(es). Fistulas must have been draining for at least 6 weeks before the screening visit. Participants with actively draining simple subcutaneous fistulas, at the time of the screening visit, are not allowed in this study.
Has inactive or mildly active luminal CD defined by meeting all of the following criteria:
- Colonoscopy, flexible sigmoidoscopy or rectoscopy performed either at screening or within the 6 months before screening, demonstrating no rectal ulcers larger than 0.5 cm. A participant who has documented rectal ulcers larger than 0.5 cm within the 6 months before screening but has undergone subsequent treatment may be eligible if there are no rectal ulcers larger than 0.5 cm on a sigmoidoscopy or rectoscopy performed after treatment or at the time of screening.
- The improvement of, or no worsening in stool frequency, sustained for 1 week or more, in the interval between the colonoscopy, flexible sigmoidoscopy or rectoscopy in inclusion criteria 4(a) and the screening visit.
- No initiation or intensification of treatment with corticosteroids, immunosuppressants, or monoclonal antibody dose regimen between the colonoscopy, flexible sigmoidoscopy or rectoscopy in inclusion criteria 4(a) and the screening visit.
Exclusion Criteria:
- Has received any investigational compound within 12 weeks/84 days before screening.
- Has received darvadstrocel/eASC in a previous clinical study or as a therapeutic agent.
- The participant weighs <10 kg at screening.
- Has concomitant perianal fistula(s) with only internal or external opening(s).
- Has concomitant internal fistula(s) such as ileo-vesical, rectovaginal or ileo-colonic fistula(s).
- Has an abscess >2 cm, unless resolved in the preparation procedure.
- Has rectal and/or anal stenosis, and/or active proctitis, which would restrict the surgical procedure.
- The participant underwent surgery for the fistula other than drainage or seton placement.
- Has diverting stomas.
- Has ongoing systemic corticosteroid treatment or has been treated with systemic corticosteroids within 4 weeks before screening.
- The participant requires new treatment with immunosuppressants/anti-TNF agents during the screening period.
- The participant has known or suspected COVID-19 by the investigator within the past 2 months (additional testing may be performed at the discretion of the investigator). Positive antibody testing for COVID without other evidence of current or recent active infection does not exclude participation. Participants who were in screening at the time that COVID-19-related factors resulted in discontinuation may also be rescreened with approval of the sponsor or designee.
- The participant requires surgery in the perianal region for reasons other than fistulas at the time of screening or foreseen either during the study and/or during the 24 weeks after treatment administration.
- Has malignant tumor or a prior history of any malignant tumor, including any type of fistula carcinoma.
- Has current or recent (within 3 months before the screening) history of abnormal, severe, progressive, uncontrolled hepatic, hematologic, gastrointestinal (except CD), endocrine, pulmonary, cardiac, neurological, psychiatric, or cerebral disease.
- Has either congenital or acquired immunodeficiencies, including participants known to be HIV carriers or participants with, in the judgment of the investigator, are suspected to have monogenic inflammatory bowel disease.
- Has previously received a bone marrow transplant.
- Has a contraindication to MRI scan or other planned study procedures.
- Has a contraindication to the anesthetic procedure.
- Had major surgery or severe trauma within 6 months before the screening visit.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Darvadstrocel
Darvadstrocel (Cx601), 24 mL suspension of 120 million cells as a perilesional injection, once on Day 0.
|
Darvadstrocel perilesional injection.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants who Achieve Combined Remission
Time Frame: 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 abscess(es) >2 cm (in at least 2 dimensions) of the treated perianal fistula(s) confirmed by central magnetic resonance imaging (MRI) assessment.
|
Week 24
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants who Achieve Clinical Remission
Time Frame: Up to Week 52
|
Clinical remission is defined as the closure of all treated external openings that were draining at baseline despite gentle finger compression.
|
Up to Week 52
|
Percentage of Participants who Achieve Clinical Response
Time Frame: Up to 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.
|
Up to Week 52
|
Time to Clinical Remission
Time Frame: Up to Week 52
|
Time to Clinical Remission is defined as the time in weeks from treatment start to first visit at which clinical remission is observed before Week 52; where clinical remission is said to occur if a clinical assessment shows closure of all treated external openings that were draining at baseline despite gentle finger compression.
|
Up to Week 52
|
Time to Clinical Response
Time Frame: Up to Week 52
|
Time to clinical response defined as the time in weeks from treatment start to first visit at which clinical response is observed before Week 52; where clinical response is said to occur if a clinical assessment shows closure of at least 50% of all treated external openings that were draining at baseline despite gentle finger compression.
|
Up to Week 52
|
Percentage of Participants with Relapse in Participants with Combined Remission at Week 24
Time Frame: Up to Week 52
|
Relapse is defined as reopening of any of the treated fistula(s) external openings with active drainage as clinically assessed in participants who were in combined remission at Week 24.
|
Up to Week 52
|
Percentage of Participants with At Least One Adverse Event (AE)
Time Frame: Up to Week 52
|
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.
|
Up to Week 52
|
Percentage of Participants with At Least One Serious Adverse Event (SAE)
Time Frame: Up to Week 52
|
An SAE is defined as an untoward medical occurrence, significant hazard, contraindication, side effect or precaution that at any dose: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
|
Up to Week 52
|
Percentage of Participants with At Least One Adverse Event of Special Interest (AESI)
Time Frame: Up to Week 52
|
An AESI include immunogenicity/alloimmune reactions, hypersensitivity, ectopic tissue formation, medication errors, tumorigenicity, transmission of infectious agents.
|
Up to Week 52
|
Percentage of Participants with Potentially Clinically Significant Vital Sign Values
Time Frame: Up to Week 52
|
Vital signs will include body temperature (oral measurement), blood pressure (systolic and diastolic, resting more than 5 minutes), and heart rate (beats per minute).
|
Up to Week 52
|
Percentage of Participants with Potentially Clinically Significant Laboratory Values
Time Frame: Up to Week 52
|
Laboratory parameters will include hematology, biochemistry, and urinalysis.
|
Up to Week 52
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Medical Director, Takeda
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- Darvadstrocel-3004
- 2020-003193-48 (EudraCT Number)
- EMEA-001561-PIP01-13-M02 (Other Identifier: EU PIP number)
- 2023-503973-39 (Other Identifier: EU CTIS Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Crohn's Disease
-
ProgenaBiomeRecruitingCrohn Disease | Crohn Colitis | Crohn's Ileocolitis | Crohn's Gastritis | Crohn's Jejunitis | Crohn's Duodenitis | Crohn's Esophagitis | Crohn's | Crohn Disease of Ileum | Crohn Ileitis | Crohn's Disease Relapse | Crohns Disease Aggravated | Crohn Disease in Remission | Crohn's Disease of PylorusUnited States
-
Massachusetts General HospitalAmerican College of GastroenterologyNot yet recruitingInflammatory Bowel Diseases | Crohn Disease | Crohn Colitis | Crohn's Ileocolitis | Crohn's Gastritis | Crohn's Jejunitis | Crohn's Duodenitis | Crohn's EsophagitisUnited States
-
Richard Burt, MDTerminatedCROHN'S DISEASEUnited States
-
Agomab Spain S.L.RecruitingFibrostenotic Crohn's DiseaseUnited States, Italy, Poland, Spain, Denmark, Austria, Canada, Germany
-
AbbVieActive, not recruitingCrohn's Disease (CD)United States, Belgium, Canada, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Netherlands, New Zealand, Norway, Poland, Romania, Slovakia, Spain, United Kingdom
-
AbbVieActive, not recruitingCrohn's Disease (CD)United States, Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Mexico, Netherlands, Poland, Romania, Russian Federation, Slo... and more
-
University Hospital, LilleMinistry of Health, FranceTerminatedCrohn's Disease AggravatedFrance
-
TakedaRecruitingCrohn's Disease (CD)United States, Australia, Israel, Belgium, Hungary, Canada, China, Croatia, Czechia, Greece, Italy, Japan, Korea, Republic of, Poland, United Kingdom, Lithuania, Slovakia, Spain
-
Weill Medical College of Cornell UniversityThe Kenneth Rainin FoundationRecruitingCrohn's Disease (CD)United States
Clinical Trials on Darvadstrocel
-
TakedaRecruiting
-
Medical University of ViennaCompletedCrohn Disease | Fistula PerianalAustria
-
Dolores Herreros MarcosCompleted
-
TakedaCompletedCrohn's Disease | Complex Perianal FistulaUnited States, Spain, France, Belgium, Israel, Czechia, Italy, Poland, Hungary
-
TakedaCompletedComplex Perianal Fistulas in Adult Participants With Crohn's DiseaseJapan
-
TakedaTakeda Development Center Americas, Inc.Active, not recruitingCrohn's Disease | Complex Perianal FistulaIsrael, Spain, Germany, Austria, France, Czechia
-
Universidad de ZaragozaHospital Universitario Fundación Jiménez DíazCompleted
-
Masonic Cancer Center, University of MinnesotaTerminated