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

Active, not recruiting

• Conditions: Crohn Disease; Complex Perianal Fistula

• Registration Number: NCT04971525
• Lead Sponsor: Takeda

Brief Summary

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.

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 Timeline

• Study First Submitted: 2021-07-19
• Study First Submitted QC: 2021-07-19
• Study First Posted: 2021-07-21
• Study Start: 2023-04-03
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-19
• Last Update Posted: 2024-07-23
• Primary Completion: 2026-11-13
• Study Completion: 2026-11-13

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 5850

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.

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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.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Incidence Rate of Malignancies Among Participants With CPF-CD	Up to Month 96	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.
Cumulative Incidence of Malignancies Among Participants With CPF-CD	Up to Month 96	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.

Secondary Outcome Measures

Name	Time	Method
All-cause Mortality Rate Among Participants With CPF-CD	Up to Month 96
Number of Participants With CPF-CD Characterized by Pharmacological Therapies	Up to Month 96	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.
Cancer-specific Mortality Rate Among Participants With CPF-CD	Up to Month 96
Number of Participants With Comorbidities	Up to Month 96	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.
Number of Participants With Anal Fistula Surgery	Up to Month 96
Number of Participants With Colorectal Surgery	Up to Month 96	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.

Trial Locations

Locations (4)

1. Système National des Données de Santé (SNDS); 🇫🇷 Charenton-le-Pont, France

PHARMO; 🇳🇱 Utrecht, Netherlands

Estudio Nacional en Enfermedad Inflamatoria intestinal sobre Determinantes genéticos y Ambientales (ENEIDA); 🇪🇸 Madrid, Spain

Institut für angewandte Gesundheitsforschung Berlin (InGef); 🇩🇪 Berlin, Germany