Long-term Follow-up Study With Darvadstrocel in the Treatment of Complex Perianal Fistula

A Follow-up of a Phase 3 Study to Evaluate the Long-term Safety and Efficacy of Darvadstrocel in the Treatment of Complex Perianal Fistula in Subjects With Crohn's Disease Who Have Participated in ADMIRE II Study

The main aim is to follow-up on long term side effect and symptom improvement of Darvadstrocel in the treatment of complex perianal fistula in adults. Participants will not receive any drug in this study.

Study Overview

• Status: Active, not recruiting
• Conditions: Crohn's Disease; Complex Perianal Fistula
• Intervention / Treatment: Biological: Darvadstrocel

Detailed Description

The drug being tested in this study is called darvadstrocel (Cx601). Darvadstrocel is being tested to treat people who have complex perianal fistula in CD. This study will look at the long-term safety and efficacy of darvadstrocel in the treatment of complex perianal fistula in CD.

The study will enroll approximately 150 patients. Participants who received darvadstrocel or placebo in study ADMIRE-CD II (Cx601-0303, NCT03279081) and who have completed the 52 weeks of the study will be enrolled in this long-term extension study.

This multi-center study will be conducted worldwide. The overall time to participate in this study is 104 weeks (in addition to the 52 weeks on ADMIRE-CD II study). Participants will make multiple visits to the clinic and will be contacted by telephone every 3 months for a follow-up assessment. After unblinding of the ADMIRE-CD II study, the LTE study will be conducted as an open-label study. Participants will remain in the treatment group assigned in the ADMIRE-CD II study.

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2018
    • GZA Sint-Vincentius
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • Universitair Ziekenhuis Gent
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • UZ Leuven
• Czechia
  • Horovice, Czechia, 268 31
    • NH Hospital a.s.
  • Hradec Kralove, Czechia, 500 05
    • FN Hradec Kralove
• France
  • Clermont-Ferrand cedex 1, France, 63003
    • CHU de Clermont-Ferrand - Estaing
  • Paris, France, 75010
    • Hopital Saint Louis
  • Pierre Benite Cedex, France, 69495
    • Centre Hospitalier Lyon Sud
  • Rennes, France, 35033
    • CHRU Hopital de Pontchaillou - Maladies De L'Appareil Digesti
  • Ile-de-France
    • Paris, Ile-de-France, France, 75014
      • Paris St. Joseph Hospital
  • Nancy
    • Vandoeuvre Les Nancy Cedex, Nancy, France, 54511
      • CHRU de Brabois Hopitaux de Brabois
  • Nord
    • Lille, Nord, France, 59037
      • CHRU de Lille - Hopital Claude Huriez - Gastroenterologie
• Hungary
  • Budapest, Hungary, 1088
    • Semmelweis Egyetem Általános Orvostudományi Kar
  • Debrecen, Hungary, H-4032
    • Debreceni Egyetem Klinikai Kozpont Nagyerdei Campus Gyermekgyogyaszati Klinika
  • Csongrad
    • Szeged, Csongrad, Hungary, 6720
      • Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar
  • Pest
    • Budapest, Pest, Hungary, 1062
      • MH Egészségügyi Központ
• Israel
  • Haifa, Israel, 31096
    • Rambam Medical Centre
  • Tel Hashomer, Israel, 52621
    • The Chaim Sheba Medical Center
  • HaMerkaz
    • Petah Tikva, HaMerkaz, Israel, 4941492
      • Rabin Medical Center, Beilinson Hospital -Gastroenterology
  • Yerushalayim
    • Jerusalem, Yerushalayim, Israel, 9112001
      • Hadassah Medical Organization, Hadassah Medical Center, Ein-
• Italy
  • Modena, Italy, 41124
    • AOU Policlinico di Modena - Gastroenterologia
  • Roma, Italy, 00168
    • Complesso Integrato Columbus, Universita Cattolica del Sacro Cuore
  • Roma, Italy, 00168
    • PU A. Gemelli, Università Cattolica del Sacro Cuore
• Poland
  • Warszawa, Poland, 02-972
    • Wielospecjalistyczny Szpital Medicover
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50-449
      • Centrum Medyczne Melita Medical
• Spain
  • Barcelona, Spain, 08003
    • Hospital Del Mar
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Pontevedra, Spain, 36071
    • C.H.U. de Pontevedra
  • Sevilla, Spain, 21005
    • H.U.V. del Rocio
  • Baleares
    • Palma de Mallorca, Baleares, Spain, 07120
      • Hospital Universitario Son Espases
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • H.U. G.Trias i Pujol
    • Sabadell, Barcelona, Spain, 08208
      • Parc Tauli Hospital Universitari
  • Madrid
    • Fuenlabrada, Madrid, Spain, 28942
      • Hospital Universitario de Fuenlabrada
• United States
  • California
    • San Francisco, California, United States, 94115
      • University of California San Francisco
    • West Hollywood, California, United States, 90048
      • Cedar-Sinai Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School Of Medicine
  • Florida
    • Fort Lauderdale, Florida, United States, 33331
      • Cleveland Clinic Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital
    • Tampa, Florida, United States, 33613
      • AdventHealth Tampa
    • Tampa, Florida, United States, 33606
      • USF Health South Tampa Center for Advanced Healthcare
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Indiana University - Colon and Rectal
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center (KUMC) - University of Kansas Liver Center - Hepatology Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachussetts General Hospital - Gastroenterology
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic College of Medicine - Division of Colon and Rectal Surgery - Division of Colon and Rectal Surgery
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03576
      • Dartmouth Hitchcock Medical Center - Cancer Center
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center - Gastroenterology
  • New York
    • Manhasset, New York, United States, 11030
      • Northwell Health
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10075
      • Lenox Hill Hospital
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Medical Center - Surgery
  • Rhode Island
    • Providence, Rhode Island, United States, 02904
      • Brown Surgical Associates,Inc.
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center - Gastroenterology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Has participated in and completed the ADMIRE-CD II (NCT03279081) study (i.e., did not discontinue).

Exclusion Criteria:

1. Has been more than 3 months since the participant completed the ADMIRE-CD II study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Darvadstrocel; Participants who received a single dose of darvadstrocel, 120 million cells, intralesionally or darvadstrocel matching placebo previously in the ADMIRE-CD II study will be observed for efficacy and safety. No drug administration in this study.	Biological: Darvadstrocel; Allogenic expanded adipose-derived stem cells (eASCs) 5 million cells/ml - suspension for injection darvadstrocel received in previous ADMIRE-CD II study. No drug administration in this study.; Other Names: Cx601

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered an investigational medicinal product; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.	Baseline (Week 52 of ADMIRE-CD II) up to Week 156 after investigational medicinal product (IMP) administration
Number of Participants With Serious Adverse Events (SAEs)	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.	Baseline (Week 52 of ADMIRE-CD II) up to Week 156 after IMP administration
Number of Participants With Specific Adverse Events of Special Interest (AESIs)	AESIs are AEs that are not solicited local or systemic AEs, they are predefined AEs that required close monitoring and prompt reporting to the sponsor. AESIs included protocol specified immunogenicity/alloimmune reactions, tumorgenicity and ectopic tissue formation.	Baseline (Week 52 of ADMIRE-CD II) up to Week 156 after IMP administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants who Achieve Clinical Remission at Weeks 104 and 156 (After IMP Administration in ADMIRE-CD II Study)	Clinical remission is defined as closure of all treated external fistula openings that were draining at baseline of ADMIRE-CD II despite gentle finger compression.	Baseline of ADMIRE-CD II and Weeks 104 and 156
Percentage of Participants who Achieve Clinical Response at Weeks 104 and 156 (After IMP Administration in ADMIRE-CD II Study)	Clinical response is defined as closure of at least 50% of all treated external fistula openings that were draining at baseline of ADMIRE-CD II despite gentle finger compression.	Baseline of ADMIRE-CD II and Weeks 104 and 156
Percentage of Participants With Relapse	Relapse is defined as participants who were in combined remission at Week 52 of ADMIRE-CD II and who have either reopening of any of the treated fistula(s) external openings with active drainage as clinically assessed or, the development of a perianal fluid collection >2 cm of the treated perianal fistulas confirmed by centrally read magnetic resonance imaging (MRI) assessment.	Up to Week 156
Percentage of Participants who Achieve Combined Clinical Remission at Week 156 (After IMP Administration in ADMIRE-CD II Study)	Combined remission of complex perianal fistula(s) is defined as the clinical assessment of closure of all treated external openings that were draining at baseline of ADMIRE-CD II, despite gentle finger compression, and absence of collection(s) >2 cm (in at least 2 dimensions) of the treated perianal fistula(s) confirmed by centrally read blinded MRI assessment.	Baseline of ADMIRE-CD II and Week 156
Percentage of Participants With New Anal Abscess in Treated Fistula at Week 156		Week 156
Change from Baseline of ADMIRE-CD II in Scores of Discharge Items of Perianal Disease Activity Index (PDAI) Score at Weeks 104 and 156	The PDAI is a scoring system to evaluate the severity of perianal CD. From the 5-item instrument, discharge will be used. Each category is graded on a 5-point Likert scale ranging from no symptoms (score of 0) to severe symptoms (score of 4); a higher score indicates more severe disease.	Weeks 104 and 156
Change from Baseline of ADMIRE-CD II in Scores of Pain Items of Perianal Disease Activity Index (PDAI) Score at Weeks 104 and 156	The PDAI is a scoring system to evaluate the severity of perianal CD. From the 5-item instrument, pain will be used. Each category is graded on a 5-point Likert scale ranging from no symptoms (score of 0) to severe symptoms (score of 4); a higher score indicates more severe disease.	Weeks 104 and 156

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information about this study, click this link.

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2019
• Primary Completion (Estimated): March 28, 2024
• Study Completion (Estimated): March 28, 2024

Study Registration Dates

• First Submitted: August 22, 2019
• First Submitted That Met QC Criteria: August 29, 2019
• First Posted (Actual): September 3, 2019

Study Record Updates

• Last Update Posted (Estimated): January 26, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Drug therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Pathological Conditions, Anatomical; Rectal Diseases; Inflammatory Bowel Diseases; Intestinal Fistula; Digestive System Fistula; Fistula; Crohn Disease; Rectal Fistula
• Other Study ID Numbers: Darvadstrocel-3003; 2019-000333-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No