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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Crohn's Disease, Complex Perianal Fistula

Intervention / Treatment
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* Biological: Darvadstrocel


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Darvadstrocel<br>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<br>* 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.<br>* Other names: Cx601;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug therapy