Phase 3 Study of Cx601 in Participants With Complex Perianal Fistulising Crohn's Disease

• ClinicalTrials.gov Identifier: NCT03706456
• Recruitment Status: Completed
• First Posted: October 16, 2018
• Results First Posted: October 7, 2021
• Last Update Posted: March 10, 2023
• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Complex Perianal Fistulas in Adult Participants With Crohn's Disease
• Intervention: Biological: Darvadstrocel
• Enrollment: 22

Participant Flow

Recruitment Details	Participants took part in the study at 9 investigative sites in Japan from 06 March 2019 to data cut-off date: 20 July 2020. The study is ongoing.
Pre-assignment Details	Participants with a diagnosis of complex perianal fistulising Crohn's disease were enrolled to receive darvadstrocel once daily.

Arm/Group Title	Darvadstrocel 24 mL
Arm/Group Description	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.
Period Title: Overall Study
Started	22
Started	22
Completed	0
Completed	0
Not Completed	22
Reason Not Completed
Lack of Efficacy	1
Ongoing	21

Baseline Characteristics

Arm/Group Title		Darvadstrocel 24 mL
Arm/Group Description		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.
Overall Number of Baseline Participants		22
Baseline Analysis Population Description		Intent to treat (ITT) Population included all participants enrolled in the study.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	22 participants
		36.4 (10.36)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants
	Female	8 36.4%
	Male	14 63.6%
Race and Ethnicity Not Collected [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	0 participants
		[1] Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
Japan	Number Analyzed	22 participants
		22 100.0%
Height; Mean (Standard Deviation); Unit of measure: Cm
	Number Analyzed	22 participants
		166.0 (8.28)
Weight; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	22 participants
		68.33 (23.102)
Body Mass Index (BMI) [1]; Mean (Standard Deviation); Unit of measure: Kg/m^2
	Number Analyzed	22 participants
		24.59 (7.186)
		[1] Measure Description: BMI=weight (kg)/[height (m)^2].
Smoking Classification; Measure Type: Count of Participants; Unit of measure: Participants
Participants has Never Smoked	Number Analyzed	22 participants
		16 72.7%
Participants is a Current Smoker	Number Analyzed	22 participants
		2 9.1%
Participants is an Ex-Smoker	Number Analyzed	22 participants
		4 18.2%
Duration of Crohn's Disease [1]; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	22 participants
		11.3 (6.64)
		[1] Measure Description: Duration of Crohn's Disease (years) is calculated by (Date of informed consent - Date of CD Diagnosis) divided by 365.25.
Concomitant Medications [1]; Measure Type: Count of Participants; Unit of measure: Participants
Biologics Only	Number Analyzed	22 participants
		9 40.9%
Immunosuppressants Only	Number Analyzed	22 participants
		2 9.1%
Biologics+Immunosuppressants	Number Analyzed	22 participants
		7 31.8%
None of 2 Types of Concomitant Drugs	Number Analyzed	22 participants
		4 18.2%
		[1] Measure Description: Number of participants who administered concomitant medications such as biologics, immunosuppressants, biologics plus immunosuppressants, and none of two types of concomitant drugs were reported.

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Combined Remission of Perianal Fistulising Crohn's Disease (CD) at Week 24
Description	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.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT Population included all participants enrolled in the study. LOCF method was applied.

Arm/Group Title	Darvadstrocel 24 mL
Arm/Group Description:	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.
Overall Number of Participants Analyzed	22
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	59.1; (38.5 to 79.6)

2. Secondary Outcome

Title	Percentage of Participants With Clinical Remission of Perianal Fistulising CD at Week 24
Description	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.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT Population included all participants enrolled in the study. LOCF method was applied.

Arm/Group Title	Darvadstrocel 24 mL
Arm/Group Description:	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.
Overall Number of Participants Analyzed	22
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	59.1; (38.5 to 79.6)

3. Secondary Outcome

Title	Percentage of Participants With Response of Perianal Fistulising CD at Week 24
Description	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.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT Population included all participants enrolled in the study. LOCF method was applied.

Arm/Group Title	Darvadstrocel 24 mL
Arm/Group Description:	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.
Overall Number of Participants Analyzed	22
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	81.8; (65.7 to 97.9)

4. Secondary Outcome

Title	Time to Clinical Remission by Week 24
Description	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.
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Darvadstrocel 24 mL
Arm/Group Description:	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.
Overall Number of Participants Analyzed	16
Median (95% Confidence Interval); Unit of Measure: days
	30.0; (14.0 to 116.0)

5. Secondary Outcome

Title	Time to Response by Week 24
Description	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.
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Darvadstrocel 24 mL
Arm/Group Description:	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.
Overall Number of Participants Analyzed	19
Median (95% Confidence Interval); Unit of Measure: days
	18.0; (12.0 to 30.0)

6. Secondary Outcome

Title	Percentage of Participants With Relapse at Week 24 in Participants With Clinical Remission at a Previous Visit
Description	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.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT Population included all participants enrolled in the study. Overall number of participants analyzed are the participants who achieved clinical remission. LOCF method was applied.

Arm/Group Title	Darvadstrocel 24 mL
Arm/Group Description:	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.
Overall Number of Participants Analyzed	16
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	25.0; (3.8 to 46.2)

7. Secondary Outcome

Title	Time to Relapse by Week 24 in Participants With Clinical Remission at a Previous Visit
Description	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.
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Darvadstrocel 24 mL
Arm/Group Description:	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.
Overall Number of Participants Analyzed	16
Median (95% Confidence Interval); Unit of Measure: days
	NA [1]; (85.0 to NA)

[1]

Median and upper limit of 95% confidence interval was not evaluated due to low number of participants with relapse.

8. Secondary Outcome

Title	Change From Baseline in Perianal Disease Activity Index (PDAI): Total Score at Week 24
Description	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 20. Higher score indicates more severe disease. Negative change from Baseline indicates improvement.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

ITT Population included all participants enrolled in the study.

Arm/Group Title	Darvadstrocel 24 mL
Arm/Group Description:	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.
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: score on a scale
Baseline	4.8 (2.15)
Change from Baseline at Week 24	-2.4 (2.22)

9. Secondary Outcome

Title	Change From Baseline in PDAI: Discharge Sub-Score at Week 24
Description	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.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

ITT Population included all participants enrolled in the study.

Arm/Group Title	Darvadstrocel 24 mL
Arm/Group Description:	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.
Overall Number of Participants Analyzed	22
Mean (Standard Deviation); Unit of Measure: score on a scale
Baseline	0.9 (0.64)
Change from Baseline at Week 24	-0.4 (0.79)

10. Secondary Outcome

Title	Change From Baseline in PDAI: Pain Sub-Score at Week 24
Description	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.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

ITT Population included all participants enrolled in the study.

Arm/Group Title	Darvadstrocel 24 mL
Arm/Group Description:	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.
Overall Number of Participants Analyzed	22
Mean (Standard Deviation); Unit of Measure: score on a scale
Baseline	0.9 (0.92)
Change from Baseline at Week 24	-0.6 (0.90)

11. Secondary Outcome

Title	Change From Baseline in Crohn's Disease Activity Index (CDAI): Total Score at Week 24
Description	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.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

ITT Population included all participants enrolled in the study.

Arm/Group Title	Darvadstrocel 24 mL
Arm/Group Description:	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.
Overall Number of Participants Analyzed	22
Mean (Standard Deviation); Unit of Measure: score on a scale
Baseline	94.25 (60.048)
Change from Baseline at Week 24	-5.15 (47.500)

12. Secondary Outcome

Title	Change From Baseline in Van Assche Score at Week 24
Description	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 score range was from 0 to 22. Higher score means more severe disease. Negative change from Baseline indicates improvement.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

ITT Population included all participants enrolled in the study. Overall number of participants analyzed were participants with data available for analysis.

Arm/Group Title	Darvadstrocel 24 mL
Arm/Group Description:	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.
Overall Number of Participants Analyzed	18
Mean (Standard Deviation); Unit of Measure: score on a scale
Baseline	14.5 (3.99)
Change from Baseline at Week 24	-1.7 (4.35)

13. Secondary Outcome

Title	Percentage of Participants With Combined Remission at Week 52
Description	Reported data will be percentage of participants who will meet combined remission criteria 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. In case of missing values, LOCF method will be applied.
Time Frame	Week 52

Outcome Measure Data Not Reported

14. Secondary Outcome

Title	Percentage of Participants With Clinical Remission at Week 52
Description	Reported data will be percentage of participants who will meet clinical remission criteria at Week 52. In case of missing values, LOCF method will be applied.
Time Frame	Week 52

Outcome Measure Data Not Reported

15. Secondary Outcome

Title	Percentage of Participants With Response at Week 52
Description	Reported data will be percentage of participants who will meet response criteria 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. In case of missing values, LOCF method will be applied.
Time Frame	Week 52

Outcome Measure Data Not Reported

16. Secondary Outcome

Title	Time to Combined Remission by Week 52
Description	Reported data will be time to combined remission from baseline by 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.
Time Frame	Week 52

Outcome Measure Data Not Reported

17. Secondary Outcome

Title	Time to Clinical Remission by Week 52
Description	Reported data will be time to clinical remission from baseline by Week 52.
Time Frame	Week 52

Outcome Measure Data Not Reported

18. Secondary Outcome

Title	Time to Response by Week 52
Description	Reported data will be time to response from baseline by 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.
Time Frame	Week 52

Outcome Measure Data Not Reported

19. Secondary Outcome

Title	Percentage of Participants With Relapse at Week 52 in Participants With Clinical Remission at Week 24
Description	Reported data will be percentage of participants who will meet relapse criteria at Week 52 in participants with clinical 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.
Time Frame	Week 52

Outcome Measure Data Not Reported

20. Secondary Outcome

Title	Time to Relapse by Week 52 in Participants With Clinical Remission at Week 24
Description	Reported data will be time to relapse from baseline by Week 52 in participants with clinical 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.
Time Frame	Up to Week 52

Outcome Measure Data Not Reported

21. Secondary Outcome

Title	PDAI: Total Score at Week 52
Description	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 means more severe disease.
Time Frame	Week 52

Outcome Measure Data Not Reported

22. Secondary Outcome

Title	PDAI: Discharge Sub-Score at Week 52
Description	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 means more severe disease.
Time Frame	Week 52

Outcome Measure Data Not Reported

23. Secondary Outcome

Title	PDAI: Pain Sub-Score at Week 52
Description	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 means more severe disease.
Time Frame	Week 52

Outcome Measure Data Not Reported

24. Secondary Outcome

Title	CDAI: Total Score at Week 52
Description	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 range of score is more than 0. Higher score means more severe disease and especially severe disease was defined as a value of greater than 450.
Time Frame	Week 52

Outcome Measure Data Not Reported

25. Secondary Outcome

Title	Van Assche Score at Week 52
Description	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. Higher score means more severe disease.
Time Frame	Week 52

Outcome Measure Data Not Reported

Adverse Events

Time Frame	Up to data cut off: 20 July 2020 (24 weeks)
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Darvadstrocel 24 mL
Arm/Group Description	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.
All-Cause Mortality
	Darvadstrocel 24 mL
	Affected / at Risk (%)
Total	0/22 (0.00%)
Serious Adverse Events
	Darvadstrocel 24 mL
	Affected / at Risk (%)
Total	3/22 (13.64%)
Gastrointestinal disorders
Crohn's disease † 1	1/22 (4.55%)
Intestinal obstruction † 1	1/22 (4.55%)
Injury, poisoning and procedural complications
Intestinal anastomosis complication † 1	1/22 (4.55%)
1 Term from vocabulary, MedDRA 23.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Darvadstrocel 24 mL
	Affected / at Risk (%)
Total	12/22 (54.55%)
Gastrointestinal disorders
Proctalgia † 1	6/22 (27.27%)
Anal fistula † 1	3/22 (13.64%)
Infections and infestations
Nasopharyngitis † 1	4/22 (18.18%)
1 Term from vocabulary, MedDRA 23.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Study Director
• Organization: Takeda
• Phone: +1-877-825-3327
• EMail: TrialDisclosures@takeda.com

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03706456
• Other Study ID Numbers: Darvadstrocel-3002; U1111-1218-8079 ( Other Identifier: WHO ); JapicCTI-184145 ( Registry Identifier: JapicCTI ); Alofisel-3002 ( Other Identifier: Takeda )
• First Submitted: October 11, 2018
• First Posted: October 16, 2018
• Results First Submitted: July 19, 2021
• Results First Posted: October 7, 2021
• Last Update Posted: March 10, 2023