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

• ClinicalTrials.gov Identifier: NCT04075825
• Recruitment Status: Completed
• First Posted: September 3, 2019
• Last Update Posted: May 6, 2024
• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

Tracking Information

• First Submitted Date: August 22, 2019
• First Posted Date: September 3, 2019
• Last Update Posted Date: May 6, 2024
• Actual Study Start Date: November 4, 2019
• Actual Primary Completion Date: April 2, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 18, 2023)

• Number of Participants With Adverse Events (AEs) [ Time Frame: Baseline (Week 52 of ADMIRE-CD II) up to Week 156 after investigational medicinal product (IMP) administration ]
  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.
• Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Baseline (Week 52 of ADMIRE-CD II) up to Week 156 after IMP administration ]
  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.
• Number of Participants With Specific Adverse Events of Special Interest (AESIs) [ Time Frame: Baseline (Week 52 of ADMIRE-CD II) up to Week 156 after IMP administration ]
  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.

Original Primary Outcome Measures (submitted: August 29, 2019)

• Number of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to Week 156 after investigational medicinal product (IMP) administration ]
  An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a 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.
• Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Week 156 after IMP administration ]
  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.
• Number of Participants With Specific Adverse Events of Special Interest (AESIs) [ Time Frame: Baseline up to Week 156 after IMP administration ]
  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.

Current Secondary Outcome Measures (submitted: January 18, 2023)

• Percentage of Participants who Achieve Clinical Remission at Weeks 104 and 156 (After IMP Administration in ADMIRE-CD II Study) [ Time Frame: Baseline of ADMIRE-CD II and Weeks 104 and 156 ]
  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.
• Percentage of Participants who Achieve Clinical Response at Weeks 104 and 156 (After IMP Administration in ADMIRE-CD II Study) [ Time Frame: Baseline of ADMIRE-CD II and Weeks 104 and 156 ]
  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.
• Percentage of Participants With Relapse [ Time Frame: Up to Week 156 ]
  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.
• Percentage of Participants who Achieve Combined Clinical Remission at Week 156 (After IMP Administration in ADMIRE-CD II Study) [ Time Frame: Baseline of ADMIRE-CD II and Week 156 ]
  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.
• Percentage of Participants With New Anal Abscess in Treated Fistula at Week 156 [ Time Frame: 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 [ Time Frame: 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.
• Change from Baseline of ADMIRE-CD II in Scores of Pain Items of Perianal Disease Activity Index (PDAI) Score at Weeks 104 and 156 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: August 29, 2019)

• Percentage of Participants who Achieve Clinical Remission at Weeks 104 and 156 (After IMP Administration in ADMIRE-CD II Study) [ Time Frame: Baseline and Weeks 104 and 156 ]
  Clinical remission is defined as closure of all treated external fistula openings that were draining at baseline despite gentle finger compression.
• Percentage of Participants who Achieve Clinical Response at Weeks 104 and 156 (After IMP Administration in ADMIRE-CD II Study) [ Time Frame: Baseline and Weeks 104 and 156 ]
  Clinical response is defined as closure of at least 50% of all treated external fistula openings that were draining at baseline despite gentle finger compression.
• Percentage of Participants With Relapse [ Time Frame: Week 52 up to Week 104 ]
  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 clinical remission at Week 52. Or, the development of a perianal fluid collection >2 cm of the treated perianal fistulas confirmed by centrally read magnetic resonance imaging (MRI) assessment.
• Percentage of Participants who Achieve Combined Clinical Remission at Week 156 (After IMP Administration in ADMIRE-CD II Study) [ Time Frame: Baseline and Week 156 ]
  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 (ie, screening visit), 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.
• Percentage of Participants With New Anal Abscess in Treated Fistula [ Time Frame: Week 104 ]
• Change from Baseline in Scores of Discharge Items of Perianal Disease Activity Index (PDAI) Score at Weeks 104 and 156 (After IMP Administration in ADMIRE-CD II Study) [ Time Frame: 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.
• Change from Baseline in Scores of Pain Items of Perianal Disease Activity Index (PDAI) Score at Weeks 104 and 156 (After IMP Administration in ADMIRE-CD II Study) [ Time Frame: 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Long-term Follow-up Study With Darvadstrocel in the Treatment of Complex Perianal Fistula
• Official Title: 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
• Brief Summary: 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.

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
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Other

Condition

• Crohn's Disease
• Complex Perianal Fistula

Intervention

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 Name: Cx601

Study Arms

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.

Intervention: Biological: Darvadstrocel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 9, 2022): 151
• Original Estimated Enrollment (submitted: August 29, 2019): 150
• Actual Study Completion Date: April 2, 2024
• Actual Primary Completion Date: April 2, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Czechia, France, Hungary, Israel, Italy, Poland, Spain, United States

Administrative Information

• NCT Number: NCT04075825
• Other Study ID Numbers: Darvadstrocel-3003; 2019-000333-39 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• 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.
• URL: https://vivli.org/ourmember/takeda/

• Current Responsible Party: Takeda
• Original Responsible Party: Millennium Pharmaceuticals, Inc.
• Current Study Sponsor: Takeda
• Original Study Sponsor: Millennium Pharmaceuticals, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Study Director; Takeda

• PRS Account: Takeda
• Verification Date: May 2024