A Study to Check How Often People Treated With Darvadstrocel for Crohn's Disease Are Diagnosed With Cancer

An Observational European Multi-database Linkage Study to Quantify Malignancy Rates in Crohn's Disease Patients With Complex Perianal Fistula Treated With Darvadstrocel

The main aim is to learn about the risk of cancer after treatment with darvadstrocel compared to other standards of care in people with Crohn's Disease (CD).

In this study, the study doctors will review each participant's past medical records. This study is about collecting existing information only; participants will not receive treatment or need to visit a study doctor during this study.

Study Overview

• Status: Withdrawn
• Conditions: Crohn Disease; Complex Perianal Fistula

Detailed Description

This is a retrospective, non-interventional study of participants with complex perianal fistula in Crohn's disease (CPF-CD). This study will assess tumorigenicity risk and all-cause and cancer-specific mortality in participants with darvadstrocel.

The study will enroll approximately 5850 participants. Data will be collected retrospectively from European secondary data sources. Participants will be assigned to two cohorts:

• Darvadstrocel cohort
• Matched control cohort: Alternate SoC.

This multi-center trial will be conducted in France, Germany, Netherlands, and Spain. The overall duration of the study will be approximately 96 months, including index period (the time in which eligible participants are included in the study) and 12 months follow-up period.

• Study Type: Observational

Contacts and Locations

Study Locations

• France
  • Charenton-le-Pont, France, 94220
    • 1. Système National des Données de Santé (SNDS)
• Germany
  • Berlin, Germany, Berlin, Germany
    • Institut für angewandte Gesundheitsforschung Berlin (InGef)
• Netherlands
  • Utrecht, Netherlands, 3528
    • PHARMO
• Spain
  • Madrid, Spain
    • Estudio Nacional en Enfermedad Inflamatoria intestinal sobre Determinantes genéticos y Ambientales (ENEIDA)

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Participants diagnosed with CPF-CD who have been administered at least one dose of darvadstrocel and participants with CD and perianal fistula (PF) and no history of administration of darvadstrocel.

Description

Inclusion Criteria:

Darvadstrocel cohort 1. Participants will be included in the darvadstrocel cohort if they have at least one record of prescription/dispensation/administration of darvadstrocel at some point during the study period.

Comparator cohort

1. A comparator cohort of controls (matched control cohort) will be composed of participants with CD and PF randomly selected from a pool of eligible participants with no history of administration of darvadstrocel.

Exclusion Criteria:

1. Has less than 12 months of uninterrupted data within country-specific data source prior to index date.
2. Has not meet quality indicators for country-specific data source (if applicable).
3. Has diagnosis of cancer prior different from non-melanoma skin cancer to index date. This will minimise the misclassification of prevalent or metastatic cancer as incident cases for the analysis of the study objectives.
4. Has diagnosis of ulcerative colitis at any point during the study period and medical history period. This will avoid potential ascertainment bias as there is currently no gold standard for differential diagnosis in IBD. Approximately 5 percent (%) to 15% of cases do not meet strict criteria for either ulcerative colitis (UC) or CD and in up to 14% of participants classified as UC and CD, the diagnosis changes over time.
5. Has record of proctectomy or colectomy prior to index date. Proctectomy and colectomy are considered "last chance" surgery options for anal fistulas or other complications of CD. These participants are not the target population for darvadstrocel. They would not be eligible for darvadstrocel administration and loss of their gastrointestinal tract would affect the risk of colorectal cancer; the most common cancer associated with CD.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Darvadstrocel Cohort; Participants diagnosed with CPF-CD, who administered at least one dose of darvadstrocel in fistula tract tissue under surgical environment will be observed.
Matched Control Cohort: Standard of Care (SoC); Participants diagnosed with CPF-CD with no history of administration of darvadstrocel, matched age at index date (within 3 years), sex and if feasible, complex perianal fistula (CPF) diagnosis (within 1 year) to individuals in the darvadstrocel cohort who received the alternative Standard of Care (SoC), which varies from country to country and according to local centre expertise will be observed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rate of Malignancies Among Participants With CPF-CD	Incidence rate of malignancies will be calculated as the number of newly observed cases divided by the person-years of follow-up during that period.	Up to Month 96
Cumulative Incidence of Malignancies Among Participants With CPF-CD	Cumulative incidence rate within a period will be calculated as the ratio of newly observed cases divided by the population at risk during that period.	Up to Month 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Anal Fistula Surgery		Up to Month 96
Number of Participants With Colorectal Surgery	Colorectal surgery such as colectomy and proctectomy modify colorectal cancer risk. Colorectal surgery will be identified using procedure codes specific to each country-specific data source.	Up to Month 96
Number of Participants With Comorbidities	Comorbidities will be identified using International Classification of Diseases 10th revision (ICD-10 codes) (or country specific modifications) within hospital settings in each country-specific data source.	Up to Month 96
All-cause Mortality Rate Among Participants With CPF-CD		Up to Month 96
Cancer-specific Mortality Rate Among Participants With CPF-CD		Up to Month 96
Number of Participants With CPF-CD Characterized by Pharmacological Therapies	Thiopurines and methotrexate have been found to increase the risk of lymphoma and skin cancer. These drugs will be identified in outpatient prescription data using Anatomical Therapeutic Chemical (ATC) codes. In the case of in-hospital administered drugs, such as anti-tumour necrosis factor's (anti-TNF) and biologics, drugs will be defined using relevant ATC codes and/or procedure codes available in the hospital records.	Up to Month 96

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link.

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: July 19, 2021
• First Submitted That Met QC Criteria: July 19, 2021
• First Posted (Actual): July 21, 2021

Study Record Updates

• Last Update Posted (Estimated): July 8, 2025
• Last Update Submitted That Met QC Criteria: July 2, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease; Fistula
• Other Study ID Numbers: Alofisel-5005

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