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

Takeda (Industry)
Overall Status
Not yet recruiting
CT.gov ID

Study Details

Study Description

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.

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.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    This is a retrospective, non-interventional study of participants with CD and CPAF. This study will assess tumorigenicity risk and all-cause and cancer-specific mortality in participants with darvadstrocel.

    The study will enroll approximately 13,080 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 Design

    Study Type:
    Anticipated Enrollment :
    13080 participants
    Observational Model:
    Time Perspective:
    Official Title:
    An Observational European Multi-database Linkage Study to Quantify Malignancy Rates in Crohn's Disease Patients With Complex Perianal Fistula Treated With Darvadstrocel
    Anticipated Study Start Date :
    Jan 31, 2023
    Anticipated Primary Completion Date :
    Dec 31, 2025
    Anticipated Study Completion Date :
    Oct 29, 2027

    Arms and Interventions

    Arm Intervention/Treatment
    Darvadstrocel Cohort

    Participants diagnosed with CD and CPAF, 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 CD and PAF with no history of administration of darvadstrocel, matched age at index date (within 3 years), time from CD diagnosis (within 1 year), and sex 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.

    Outcome Measures

    Primary Outcome Measures

    1. Occurrence of Malignancies in Crohn's Disease (CD) Participants With Perianal Fistula (PAF) [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.

    2. Cumulative Occurrence of Malignancies in CD Participants With PAF [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

    1. All-cause Mortality Rate in CD Participants With PAF [Up to Month 96]

    2. Cancer-specific Mortality rate in CD Participants With PAF [Up to Month 96]

    3. Number of Participants With Anal Fistula Surgery [Up to Month 96]

    4. 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.

    5. Number of CD Participants With PAF 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.

    6. 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.

    Eligibility Criteria


    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Accepts Healthy Volunteers:
    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 PAF randomly selected from a pool of eligible participants with no history of administration of darvadstrocel.

    2. Has any other management of CPAF different to darvadstrocel, from no treatment to any other treatment.

    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 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.

    Contacts and Locations


    No locations specified.

    Sponsors and Collaborators

    • Takeda


    • Study Director: Study Director, Takeda

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:


    None provided.
    Responsible Party:
    ClinicalTrials.gov Identifier:
    Other Study ID Numbers:
    • Alofisel-5005
    First Posted:
    Jul 21, 2021
    Last Update Posted:
    Jul 11, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Plan to Share IPD:
    Studies a U.S. FDA-regulated Drug Product:
    Studies a U.S. FDA-regulated Device Product:
    Keywords provided by Takeda
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 11, 2022