Purpose of this study?
The purpose of this study is to evaluate the long-term safety of a single dose of darvadstrocel in participants with Crohn's disease (CD) and complex perianal fistula by evaluation of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs).
Inclusion Criteria:
Key Exclusion Criteria:
Primary outcome measures:
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.
2. 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.
3. 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.
Secondary outcome measures:
Clinical remission is defined as closure of all treated external fistula openings that were draining at baseline despite gentle finger compression.
2. 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.
3. 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.
4. 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.
5.Percentage of Participants With New Anal Abscess in Treated Fistula [ Time Frame:
Week 104 ]
6. 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.
7. 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.
Study Locations in Europe:
Belgium, Czech Republic, France, Hungary, Italy, Poland, Spain
Estimated Study Completion Date: February 28, 2024
Further information on clinicaltrials.gov with trial number NCT04075825