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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1218-8079 | Other Identifier | WHO | |
| JapicCTI-184145 | Registry Identifier | JapicCTI | |
| Alofisel-3002 | Other Identifier | Takeda |
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The purpose of this study is to evaluate the efficacy of darvadstrocel for the treatment of complex perianal fistulas in adult participants with Crohn's disease over 24 weeks.
The drug being tested in this study is called Darvadstrocel (Cx601). This study will assess the efficacy for 24 and 52 weeks, and safety for 156 weeks of darvadstrocel when administered with intralesional injection in adult participants with Crohn's disease whose complex perianal fistulas were previously treated and refractory.
The study enrolled 22 participants. All participants who will meet the criteria will be assigned to screening period for approximately 5 weeks and after that will be enrolled the treatment period which will be the day of study product administration. After the treatment period, this study will include the follow-up period for approximately 52 weeks after study product administration, and the long-term follow-up period from Week 52 to Week 156.
This multi-center trial will be conducted in Japan. The overall time to participate is totally approximately 156 weeks (3 years) from the start of treatment period plus follow-up and long-term follow-up period. Participants will make multiple visits to the clinic and a final visit 156 weeks after treatment of study product for a follow-up assessment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Darvadstrocel 24 mL | Experimental | Darvadstrocel (Cx601) 24 mL suspension of 120 million cells of expanded allogeneic adipose-derived stem cells (eASC) as an intralesional injection, once on Day 1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Darvadstrocel | Biological | Darvadstrocel cell suspension for intralesional injection. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Combined Remission of Perianal Fistulising Crohn's Disease (CD) at Week 24 | Combined remission of perianal fistulising CD is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression, and absence of collections >2 cm in the treated fistulas, confirmed by central magnetic resonance imaging (MRI) assessment at Week 24 visit. In case of missing values, last observation carried forward (LOCF) method was applied. Percentages are rounded off to the nearest decimal point. | Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Clinical Remission of Perianal Fistulising CD at Week 24 | Clinical remission of perianal fistulising CD is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression at Week 24 Visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point. |
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Inclusion Criteria:
In the opinion of the investigator, the participant is capable of understanding and complying with the protocol requirements.
The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
The participant who was diagnosed with Crohn's disease at least 6 months prior to the screening period according to the Diagnostic Criteria for Crohn's Disease issued by Research Group for Intractable Inflammatory Bowel Disease Designated as Specified Disease by the Ministry of Health, Labour and Welfare (MHLW) of Japan (revised January 2017).
The participant is either a male or female outpatient, aged 18 years or older at the time of signing the informed consent form.
The participant who has non-active or mildly active Crohn's disease defined by the Crohn's disease activity index (CDAI) =<220 evaluated at any time between Visit 1 and Visit 2.
The participant who has complex perianal fistulas with a maximum of 2 internal openings and a maximum of 3 external openings, confirmed by clinical assessment and MRI. All of the external openings must connect to internal openings. Fistula must have been draining for at least 6 weeks prior to the screening. Complex perianal fistula is defined as the one that meets 1 or more of the following criteria:
The participant whose perianal fistulas were previously treated and have shown an inadequate response (absence of closure of part or all fistula tract, or new fistula during induction treatment) or a loss of response (fistula relapse after complete closure of initial fistula, or fistula worsening after partial closure of initial fistula during maintenance treatment) while they were receiving either immunosuppressants or biologics, or having documented intolerance (occurrence, at any time, of an unacceptable level of treatment-related side effects that makes necessary treatment discontinuation) to any of these treatments administered at least approved or recommended doses during the minimum period mentioned;
A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent up to Week 52 of the study.
A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent up to Week 52 of the study.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ieda Hospital | Toyota | Aichi-ken | Japan | |||
| Fukuoka University Chikushi Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36149832 | Derived | Furukawa S, Mizushima T, Nakaya R, Shibata M, Yamaguchi T, Watanabe K, Futami K. Darvadstrocel for Complex Perianal Fistulas in Japanese Adults with Crohn's Disease: A Phase 3 Study. J Crohns Colitis. 2023 Apr 3;17(3):369-378. doi: 10.1093/ecco-jcc/jjac144. |
| Label | URL |
|---|---|
| To obtain more information on the study, click here/on this link | View source |
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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.
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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.
Participants with a diagnosis of complex perianal fistulising Crohn's disease were enrolled to receive darvadstrocel once daily.
Participants took part in the study at 9 investigative sites in Japan from 06 March 2019 to 10 February 2023.
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| ID | Title | Description |
|---|---|---|
| FG000 | Darvadstrocel 24 mL | Darvadstrocel (Cx601) 24 mL suspension of 120 million cells of expanded allogeneic adipose-derived stem cells (eASC) as an intralesional injection, once on Day 1. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Intent to treat (ITT) Population included all participants enrolled in the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Darvadstrocel 24 mL | Darvadstrocel (Cx601) 24 mL suspension of 120 million cells of eASC as an intralesional injection, once on Day 1. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Combined Remission of Perianal Fistulising Crohn's Disease (CD) at Week 24 | Combined remission of perianal fistulising CD is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression, and absence of collections >2 cm in the treated fistulas, confirmed by central magnetic resonance imaging (MRI) assessment at Week 24 visit. In case of missing values, last observation carried forward (LOCF) method was applied. Percentages are rounded off to the nearest decimal point. | ITT Population included all participants enrolled in the study. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 24 |
|
From first dose of study drug up to Week 156
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Darvadstrocel 24 mL | Darvadstrocel (Cx601) 24 mL suspension of 120 million cells of expanded allogeneic adipose-derived stem cells (eASC) as an intralesional injection, once on Day 1. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anal fistula | Gastrointestinal disorders | MedDRA 25 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acrochordon | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 25 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Takeda | +1-877-825-3327 | TrialDisclosures@takeda.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 13, 2021 | Jul 19, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 9, 2022 | Dec 19, 2023 | SAP_002.pdf |
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| Week 24 |
| Percentage of Participants With Response of Perianal Fistulising CD at Week 24 | Response of perianal fistulising CD is defined as the clinically confirmed closure of at least 50 percent of all treated external openings that were draining at Screening despite gentle finger compression at Week 24 visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point. | Week 24 |
| Time to Clinical Remission of Perianal Fistulising CD by Week 24 | Time to clinical remission is defined as the time from the study product administration to the first visit by which clinical remission is observed. Clinical remission is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression. | Up to Week 24 |
| Time to Response of Perianal Fistulising CD by Week 24 | Time to response is defined as the time from the study product administration to the first visit by which response is observed. Response is defined as the clinically confirmed closure of at least 50 percent of all treated external openings that were draining at Screening despite gentle finger compression. | Up to Week 24 |
| Percentage of Participants With Relapse of Perianal Fistulising CD at Week 24 in Participants With Clinical Remission at a Previous Visit | Relapse is defined as the clinically confirmed reopening of any of the treated external openings with active drainage, or the development of a collection >2 cm in the treated fistulas confirmed by central MRI assessment in participants who achieved clinical remission before Week 24. LOCF method was applied. Percentages are rounded off to the nearest decimal point. | Week 24 |
| Time to Relapse of Perianal Fistulising CD by Week 24 in Participants With Clinical Remission at a Previous Visit | Time to Relapse is defined as the time from the first visit by which clinical remission is observed to the first visit by which relapse is observed. Relapse is defined as the clinically confirmed reopening of any of the treated external openings with active drainage, or the development of a collection >2 cm in the treated fistulas confirmed by central MRI assessment. | Up to Week 24 |
| Change From Baseline in Perianal Disease Activity Index (PDAI): Total Score at Week 24 | The PDAI is a scoring system to evaluate the severity of perianal lesion associated with Crohn's disease. It includes the following 5 items: (a) Discharge; (b) Pain; (c) Restriction of sexual activity; (d) Type of perianal disease; and (e) Degree of induration. Each item is graded on a 5-point scale where 0 indicates no symptoms and 4 indicates severe symptoms and total range of score is from 0 to 20. Higher score indicates more severe disease. Negative change from Baseline indicates improvement. | Baseline and Week 24 |
| Change From Baseline in PDAI: Discharge Sub-Score at Week 24 | The PDAI is a scoring system to evaluate the severity of perianal lesion associated with Crohn's disease. It includes the following 5 items: (a) Discharge; (b) Pain; (c) Restriction of sexual activity; (d) Type of perianal disease; and (e) Degree of induration. The discharge item is graded on a 5-point scale where 0 indicates no symptoms and 4 indicates severe symptoms and total range of score is from 0 to 4. Higher score indicates more severe disease. Negative change from Baseline indicates improvement. | Baseline and Week 24 |
| Change From Baseline in PDAI: Pain Sub-Score at Week 24 | The PDAI is a scoring system to evaluate the severity of perianal lesion associated with Crohn's disease. It includes the following 5 items: (a) Discharge; (b) Pain; (c) Restriction of sexual activity; (d) Type of perianal disease; and (e) Degree of induration. The pain item is graded on a 5-point scale where 0 indicates no symptoms and 4 indicates severe symptoms and total range of score is from 0 to 4. Higher score indicates more severe disease. Negative change from Baseline indicates improvement. | Baseline and Week 24 |
| Change From Baseline in Crohn's Disease Activity Index (CDAI): Total Score at Week 24 | CDAI score is calculated from the following 8 items: (a) Number of liquid or very soft stools; (b) Abdominal pain; (c) General wellbeing; (d) Extraintestinal complications; (e) Antidiarrhoeal drugs; (f) Abdominal mass; (g) Hematocrit; and (h) Body weight. Scores of some items in CDAI are calculated based on patient diary. Total score ranges from 0 to 600. Higher score means more severe disease and especially severe disease was defined as a value of greater than 450. Negative change from Baseline indicates improvement. | Baseline and Week 24 |
| Change From Baseline in Van Assche Score at Week 24 | The Van Assche score represents the magnetic resonance imaging (MRI)- based severity of perianal lesion associated with Crohn's disease. Based on MRI data, the number, location and extension of fistula tracts, hyperintensity on T2-weighted images, presence or absence of collections (cavities >3 mm in diameter), and rectal wall involvement will be evaluated. The score range was from 0 to 22. Higher score means more severe disease. Negative change from Baseline indicates improvement. | Baseline and Week 24 |
| Percentage of Participants With Combined Remission of Perianal Fistulising CD at Week 52 | Combined remission is defined as the clinically confirmed closure of all treated external openings that were draining at the screening despite gentle finger compression, and absence of collections >2 cm in the treated fistulas which is confirmed by the central MRI assessment at Week 52 visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point. | Week 52 |
| Percentage of Participants With Clinical Remission of Perianal Fistulising CD at Week 52 | Clinical remission is defined as the clinically confirmed closure of all treated external openings that were draining at screening despite gentle finger compression at Week 52 visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point. | Week 52 |
| Percentage of Participants With Response of Perianal Fistulising CD at Week 52 | Response is defined as the clinically confirmed closure of at least 50 percent of all treated external openings that were draining at the screening despite gentle finger compression at Week 52 visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point. | Week 52 |
| Time to Combined Remission of Perianal Fistulising CD by Week 52 | Time to combined remission is defined as the time from the study product administration to the first visit by which combined remission is observed. Combined remission is defined as the clinically confirmed closure of all treated external openings that were draining at the screening despite gentle finger compression, and absence of collections >2 cm in the treated fistulas which is confirmed by the central MRI assessment. | Up to Week 52 |
| Time to Clinical Remission of Perianal Fistulising CD by Week 52 | Time to clinical remission is defined as the time from the study product administration to the first visit by which clinical remission is observed. Clinical remission is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression. | Up to Week 52 |
| Time to Response of Perianal Fistulising CD by Week 52 | Time to response is defined as the time from the study product administration to the first visit by which response is observed. Response is defined as the clinically confirmed closure of at least 50 percent of all treated external openings that were draining at the Screening despite gentle finger compression. | Up to Week 52 |
| Percentage of Participants With Relapse of Perianal Fistulising CD at Week 52 in Participants With Combined Remission at Week 24 | Relapse is defined as the clinically confirmed reopening of any of the treated external openings with active drainage, or the development of a collection >2 cm in the treated fistulas confirmed by central MRI assessment in participants who achieved combined remission at Week 24. Combined remission is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression, and absence of collections >2 cm in the treated fistulas, confirmed by the central MRI assessment. LOCF method was applied. Percentages are rounded off to the nearest decimal point. | Week 52 |
| Time to Relapse of Perianal Fistulising CD by Week 52 in Participants With Combined Remission at Week 24 | Time to relapse by Week 52 in participants who achieved combined remission at Week 24 is defined as the time from the combined remission at Week 24 to the first visit by which relapse is observed. Relapse is defined as the clinically confirmed reopening of any of the treated external openings with active drainage, or the development of a collection >2 cm in the treated fistulas confirmed by central MRI assessment in participants who achieved combined remission at Week 24. Combined remission is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression, and absence of collections >2 cm in the treated fistulas, confirmed by the central MRI assessment. | Up to Week 52 |
| Change From Baseline in PDAI: Total Score at Week 52 | The PDAI is a scoring system to evaluate the severity of perianal lesion associated with Crohn's disease. It includes the following 5 items: (a) Discharge; (b) Pain; (c) Restriction of sexual activity; (d) Type of perianal disease; and (e) Degree of induration. Each item is graded on a 5-point scale ranging from no symptoms (score of 0) to severe symptoms (score of 4) and total range of score is from 0 to 20. Higher score indicates more severe disease. Negative change from Baseline indicates improvement. | Baseline and Week 52 |
| Change From Baseline in PDAI: Discharge Sub-Score at Week 52 | The PDAI is a scoring system to evaluate the severity of perianal lesion associated with Crohn's disease. It includes the following 5 items: (a) Discharge; (b) Pain; (c) Restriction of sexual activity; (d) Type of perianal disease; and (e) Degree of induration. The discharge item is graded on a 5-point scale ranging from no symptoms (score of 0) to severe symptoms (score of 4) and total range of score is from 0 to 20. Higher score indicates more severe disease. Negative change from Baseline indicates improvement. | Baseline and Week 52 |
| Change From Baseline in PDAI: Pain Sub-Score at Week 52 | The PDAI is a scoring system to evaluate the severity of perianal lesion associated with Crohn's disease. It includes the following 5 items: (a) Discharge; (b) Pain; (c) Restriction of sexual activity; (d) Type of perianal disease; and (e) Degree of induration. The pain item is graded on a 5-point scale ranging from no symptoms (score of 0) to severe symptoms (score of 4) and total range of score is from 0 to 20. Higher score indicates more severe disease. Negative change from Baseline indicates improvement. | Baseline and Week 52 |
| Change From Baseline in CDAI: Total Score at Week 52 | CDAI score is calculated from the following 8 items: (a) Number of liquid or very soft stools; (b) Abdominal pain; (c) General wellbeing; (d) Extraintestinal complications; (e) Antidiarrhoeal drugs; (f) Abdominal mass; (g) Hematocrit; and (h) Body weight. Scores of some items in CDAI are calculated based on patient diary. Total score ranges from 0 to 600. Higher score indicates more severe disease and especially severe disease was defined as a value of greater than 450. Negative change from Baseline indicates improvement. | Baseline and Week 52 |
| Change From Baseline in Van Assche Total Score at Week 52 | The Van Assche score represents the MRI-based severity of perianal lesion associated with Crohn's disease. Based on MRI data, the number, location and extension of fistula tracts, hyperintensity on T2-weighted images, presence or absence of collections (cavities >3 mm in diameter), and rectal wall involvement will be evaluated. The total score ranges from 0 to 22. Higher score indicates more severe disease. Negative change from Baseline indicates improvement. | Baseline and Week 52 |
| Chikushino-shi |
| Fukuoka |
| Japan |
| Sapporo Higashi Tokushukai Hospital | Sapporo | Hokkaido | Japan |
| Hyogo College of Medicine | Nishinomiya | Hyōgo | Japan |
| Yokohama Municipal Citizen's Hospital | Yokohama | Kanagawa | Japan |
| Mie University Hospital | Tsu | Mie-ken | Japan |
| Tohoku Rosai Hospital | Sendai | Miyagi | Japan |
| Tohoku University Hospital | Sendai | Miyagi | Japan |
| Osaka University Hospital | Suita | Osaka | Japan |
| JCHO Tokyo Yamate Medical Center | Shinjuku | Tokyo | Japan |
| Coloproctology Center Takano Hospital | Kumamoto | Japan |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Height | Mean | Standard Deviation | centimeters (cm) |
|
| Weight | Mean | Standard Deviation | kilograms (kg) |
|
| Body Mass Index (BMI) | BMI=weight (kg)/[height (m)^2]. | Mean | Standard Deviation | kilogram per square meter (kg/m^2) |
|
| Smoking Classification | Count of Participants | Participants |
|
| Duration of Crohn's Disease | Duration of Crohn's Disease (years) is calculated by (Date of informed consent - Date of CD Diagnosis) divided by 365.25. | Mean | Standard Deviation | years |
|
| Concomitant Medications | Number of participants who administered concomitant medications such as biologics, immunosuppressants, biologics plus immunosuppressants, and none of two types of concomitant drugs were reported. | Count of Participants | Participants |
|
|
|
| Secondary | Percentage of Participants With Clinical Remission of Perianal Fistulising CD at Week 24 | Clinical remission of perianal fistulising CD is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression at Week 24 Visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point. | ITT Population included all participants enrolled in the study. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 24 |
|
|
|
| Secondary | Percentage of Participants With Response of Perianal Fistulising CD at Week 24 | Response of perianal fistulising CD is defined as the clinically confirmed closure of at least 50 percent of all treated external openings that were draining at Screening despite gentle finger compression at Week 24 visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point. | ITT Population included all participants enrolled in the study. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 24 |
|
|
|
| Secondary | Time to Clinical Remission of Perianal Fistulising CD by Week 24 | Time to clinical remission is defined as the time from the study product administration to the first visit by which clinical remission is observed. Clinical remission is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression. | ITT Population included all participants enrolled in the study. Overall number of participants analyzed are the participants with clinical remission at least once during the 24-week period. | Posted | Median | 95% Confidence Interval | days | Up to Week 24 |
|
|
|
| Secondary | Time to Response of Perianal Fistulising CD by Week 24 | Time to response is defined as the time from the study product administration to the first visit by which response is observed. Response is defined as the clinically confirmed closure of at least 50 percent of all treated external openings that were draining at Screening despite gentle finger compression. | ITT Population included all participants enrolled in the study. Overall number of participants analyzed are the participants with response at least once during the 24-week period. | Posted | Median | 95% Confidence Interval | days | Up to Week 24 |
|
|
|
| Secondary | Percentage of Participants With Relapse of Perianal Fistulising CD at Week 24 in Participants With Clinical Remission at a Previous Visit | Relapse is defined as the clinically confirmed reopening of any of the treated external openings with active drainage, or the development of a collection >2 cm in the treated fistulas confirmed by central MRI assessment in participants who achieved clinical remission before Week 24. LOCF method was applied. Percentages are rounded off to the nearest decimal point. | ITT Population included all participants enrolled in the study. Overall number of participants analyzed are the participants who achieved clinical remission. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 24 |
|
|
|
| Secondary | Time to Relapse of Perianal Fistulising CD by Week 24 in Participants With Clinical Remission at a Previous Visit | Time to Relapse is defined as the time from the first visit by which clinical remission is observed to the first visit by which relapse is observed. Relapse is defined as the clinically confirmed reopening of any of the treated external openings with active drainage, or the development of a collection >2 cm in the treated fistulas confirmed by central MRI assessment. | ITT Population included all participants enrolled in the study. Overall number of participants analyzed are the participants with clinical remission at least once during the 24-week period. | Posted | Median | 95% Confidence Interval | days | Up to Week 24 |
|
|
|
| Secondary | Change From Baseline in Perianal Disease Activity Index (PDAI): Total Score at Week 24 | The PDAI is a scoring system to evaluate the severity of perianal lesion associated with Crohn's disease. It includes the following 5 items: (a) Discharge; (b) Pain; (c) Restriction of sexual activity; (d) Type of perianal disease; and (e) Degree of induration. Each item is graded on a 5-point scale where 0 indicates no symptoms and 4 indicates severe symptoms and total range of score is from 0 to 20. Higher score indicates more severe disease. Negative change from Baseline indicates improvement. | ITT Population included all participants enrolled in the study. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 24 |
|
|
|
| Secondary | Change From Baseline in PDAI: Discharge Sub-Score at Week 24 | The PDAI is a scoring system to evaluate the severity of perianal lesion associated with Crohn's disease. It includes the following 5 items: (a) Discharge; (b) Pain; (c) Restriction of sexual activity; (d) Type of perianal disease; and (e) Degree of induration. The discharge item is graded on a 5-point scale where 0 indicates no symptoms and 4 indicates severe symptoms and total range of score is from 0 to 4. Higher score indicates more severe disease. Negative change from Baseline indicates improvement. | ITT Population included all participants enrolled in the study. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 24 |
|
|
|
| Secondary | Change From Baseline in PDAI: Pain Sub-Score at Week 24 | The PDAI is a scoring system to evaluate the severity of perianal lesion associated with Crohn's disease. It includes the following 5 items: (a) Discharge; (b) Pain; (c) Restriction of sexual activity; (d) Type of perianal disease; and (e) Degree of induration. The pain item is graded on a 5-point scale where 0 indicates no symptoms and 4 indicates severe symptoms and total range of score is from 0 to 4. Higher score indicates more severe disease. Negative change from Baseline indicates improvement. | ITT Population included all participants enrolled in the study. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 24 |
|
|
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| Secondary | Change From Baseline in Crohn's Disease Activity Index (CDAI): Total Score at Week 24 | CDAI score is calculated from the following 8 items: (a) Number of liquid or very soft stools; (b) Abdominal pain; (c) General wellbeing; (d) Extraintestinal complications; (e) Antidiarrhoeal drugs; (f) Abdominal mass; (g) Hematocrit; and (h) Body weight. Scores of some items in CDAI are calculated based on patient diary. Total score ranges from 0 to 600. Higher score means more severe disease and especially severe disease was defined as a value of greater than 450. Negative change from Baseline indicates improvement. | ITT Population included all participants enrolled in the study. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 24 |
|
|
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| Secondary | Change From Baseline in Van Assche Score at Week 24 | The Van Assche score represents the magnetic resonance imaging (MRI)- based severity of perianal lesion associated with Crohn's disease. Based on MRI data, the number, location and extension of fistula tracts, hyperintensity on T2-weighted images, presence or absence of collections (cavities >3 mm in diameter), and rectal wall involvement will be evaluated. The score range was from 0 to 22. Higher score means more severe disease. Negative change from Baseline indicates improvement. | ITT Population included all participants enrolled in the study. Overall number of participants analyzed were participants with data available for analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 24 |
|
|
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| Secondary | Percentage of Participants With Combined Remission of Perianal Fistulising CD at Week 52 | Combined remission is defined as the clinically confirmed closure of all treated external openings that were draining at the screening despite gentle finger compression, and absence of collections >2 cm in the treated fistulas which is confirmed by the central MRI assessment at Week 52 visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point. | ITT Population included all participants enrolled in the study. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 52 |
|
|
|
| Secondary | Percentage of Participants With Clinical Remission of Perianal Fistulising CD at Week 52 | Clinical remission is defined as the clinically confirmed closure of all treated external openings that were draining at screening despite gentle finger compression at Week 52 visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point. | ITT Population included all participants enrolled in the study. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 52 |
|
|
|
| Secondary | Percentage of Participants With Response of Perianal Fistulising CD at Week 52 | Response is defined as the clinically confirmed closure of at least 50 percent of all treated external openings that were draining at the screening despite gentle finger compression at Week 52 visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point. | ITT Population included all participants enrolled in the study. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 52 |
|
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| Secondary | Time to Combined Remission of Perianal Fistulising CD by Week 52 | Time to combined remission is defined as the time from the study product administration to the first visit by which combined remission is observed. Combined remission is defined as the clinically confirmed closure of all treated external openings that were draining at the screening despite gentle finger compression, and absence of collections >2 cm in the treated fistulas which is confirmed by the central MRI assessment. | ITT Population included all participants enrolled in the study. Overall number analyzed is the number of participants who achieved combined remission at least once during the 52-week period. | Posted | Median | 95% Confidence Interval | days | Up to Week 52 |
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| Secondary | Time to Clinical Remission of Perianal Fistulising CD by Week 52 | Time to clinical remission is defined as the time from the study product administration to the first visit by which clinical remission is observed. Clinical remission is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression. | ITT Population included all participants enrolled in the study. Overall number analyzed is the number of participants who achieved clinical remission at least once during the 52-week period. | Posted | Median | 95% Confidence Interval | days | Up to Week 52 |
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| Secondary | Time to Response of Perianal Fistulising CD by Week 52 | Time to response is defined as the time from the study product administration to the first visit by which response is observed. Response is defined as the clinically confirmed closure of at least 50 percent of all treated external openings that were draining at the Screening despite gentle finger compression. | ITT Population included all participants enrolled in the study. Overall number analyzed is the number of participants who achieved response at least once during the 52-week period. | Posted | Median | 95% Confidence Interval | days | Up to Week 52 |
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| Secondary | Percentage of Participants With Relapse of Perianal Fistulising CD at Week 52 in Participants With Combined Remission at Week 24 | Relapse is defined as the clinically confirmed reopening of any of the treated external openings with active drainage, or the development of a collection >2 cm in the treated fistulas confirmed by central MRI assessment in participants who achieved combined remission at Week 24. Combined remission is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression, and absence of collections >2 cm in the treated fistulas, confirmed by the central MRI assessment. LOCF method was applied. Percentages are rounded off to the nearest decimal point. | ITT Population included all participants enrolled in the study. Overall number analyzed is the number of participants with combined remission at Week 24. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 52 |
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| Secondary | Time to Relapse of Perianal Fistulising CD by Week 52 in Participants With Combined Remission at Week 24 | Time to relapse by Week 52 in participants who achieved combined remission at Week 24 is defined as the time from the combined remission at Week 24 to the first visit by which relapse is observed. Relapse is defined as the clinically confirmed reopening of any of the treated external openings with active drainage, or the development of a collection >2 cm in the treated fistulas confirmed by central MRI assessment in participants who achieved combined remission at Week 24. Combined remission is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression, and absence of collections >2 cm in the treated fistulas, confirmed by the central MRI assessment. | ITT Population included all participants enrolled in the study. Overall number analyzed is the number of participants with combined remission at Week 24. | Posted | Median | 95% Confidence Interval | days | Up to Week 52 |
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| Secondary | Change From Baseline in PDAI: Total Score at Week 52 | The PDAI is a scoring system to evaluate the severity of perianal lesion associated with Crohn's disease. It includes the following 5 items: (a) Discharge; (b) Pain; (c) Restriction of sexual activity; (d) Type of perianal disease; and (e) Degree of induration. Each item is graded on a 5-point scale ranging from no symptoms (score of 0) to severe symptoms (score of 4) and total range of score is from 0 to 20. Higher score indicates more severe disease. Negative change from Baseline indicates improvement. | ITT Population included all participants enrolled in the study. Overall number analyzed is the number of participants with data available for analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 52 |
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| Secondary | Change From Baseline in PDAI: Discharge Sub-Score at Week 52 | The PDAI is a scoring system to evaluate the severity of perianal lesion associated with Crohn's disease. It includes the following 5 items: (a) Discharge; (b) Pain; (c) Restriction of sexual activity; (d) Type of perianal disease; and (e) Degree of induration. The discharge item is graded on a 5-point scale ranging from no symptoms (score of 0) to severe symptoms (score of 4) and total range of score is from 0 to 20. Higher score indicates more severe disease. Negative change from Baseline indicates improvement. | ITT Population included all participants enrolled in the study. Overall number analyzed is the number of participants with data available for analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 52 |
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| Secondary | Change From Baseline in PDAI: Pain Sub-Score at Week 52 | The PDAI is a scoring system to evaluate the severity of perianal lesion associated with Crohn's disease. It includes the following 5 items: (a) Discharge; (b) Pain; (c) Restriction of sexual activity; (d) Type of perianal disease; and (e) Degree of induration. The pain item is graded on a 5-point scale ranging from no symptoms (score of 0) to severe symptoms (score of 4) and total range of score is from 0 to 20. Higher score indicates more severe disease. Negative change from Baseline indicates improvement. | ITT Population included all participants enrolled in the study. Overall number analyzed is the number of participants with data available for analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 52 |
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| Secondary | Change From Baseline in CDAI: Total Score at Week 52 | CDAI score is calculated from the following 8 items: (a) Number of liquid or very soft stools; (b) Abdominal pain; (c) General wellbeing; (d) Extraintestinal complications; (e) Antidiarrhoeal drugs; (f) Abdominal mass; (g) Hematocrit; and (h) Body weight. Scores of some items in CDAI are calculated based on patient diary. Total score ranges from 0 to 600. Higher score indicates more severe disease and especially severe disease was defined as a value of greater than 450. Negative change from Baseline indicates improvement. | ITT Population included all participants enrolled in the study. Overall number analyzed is the number of participants with data available for analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 52 |
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| Secondary | Change From Baseline in Van Assche Total Score at Week 52 | The Van Assche score represents the MRI-based severity of perianal lesion associated with Crohn's disease. Based on MRI data, the number, location and extension of fistula tracts, hyperintensity on T2-weighted images, presence or absence of collections (cavities >3 mm in diameter), and rectal wall involvement will be evaluated. The total score ranges from 0 to 22. Higher score indicates more severe disease. Negative change from Baseline indicates improvement. | ITT Population included all participants enrolled in the study. Overall number analyzed is the number of participants with data available for analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 52 |
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| 0 |
| 22 |
| 11 |
| 22 |
| 18 |
| 22 |
| COVID-19 | Infections and infestations | MedDRA 25 | Systematic Assessment |
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| Calculus urinary | Renal and urinary disorders | MedDRA 25 | Systematic Assessment |
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| Crohn's disease | Gastrointestinal disorders | MedDRA 25 | Systematic Assessment |
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| Intestinal anastomosis complication | Injury, poisoning and procedural complications | MedDRA 25 | Systematic Assessment |
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| Intestinal obstruction | Gastrointestinal disorders | MedDRA 25 | Systematic Assessment |
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| Premature labour | Pregnancy, puerperium and perinatal conditions | MedDRA 25 | Systematic Assessment |
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| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 25 | Systematic Assessment |
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| Tubulointerstitial nephritis | Renal and urinary disorders | MedDRA 25 | Systematic Assessment |
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| Anal fistula | Gastrointestinal disorders | MedDRA 25 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 25 | Systematic Assessment |
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| Cheilitis | Gastrointestinal disorders | MedDRA 25 | Systematic Assessment |
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| Dental caries | Gastrointestinal disorders | MedDRA 25 | Systematic Assessment |
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| Fistula | Musculoskeletal and connective tissue disorders | MedDRA 25 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 25 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 25 | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA 25 | Systematic Assessment |
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| Proctalgia | Gastrointestinal disorders | MedDRA 25 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 25 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA 25 | Systematic Assessment |
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The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.