A Phase 3, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of Darvadstrocel in the Treatment of Complex Perianal Fistula in Pediatric Subjects with Crohn's Disease over a Period of 24 Weeks and an Extended Follow-up Period for a Total of up to 52 Weeks
A Study of Darvadstrocel for Treating of Complex Perianal Fistula in Children and Teenagers With Crohn's Disease
Shikamura Mitsuhiro
Takeda Pharmaceutical Company Limited
1-1, Doshomachi 4-chome, Chuo-ku, Osaka
+81-662042111
smb.Japanclinicalstudydisclosure@takeda.com
Contact for Clinical Trial Information
Takeda Pharmaceutical Company Limited
1-1, Doshomachi 4-chome, Chuo-ku, Osaka
+81-662042111
smb.Japanclinicalstudydisclosure@takeda.com
Not Recruiting
June. 30, 2021
June. 30, 2021
7
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
1. Has a CD diagnosis based on accepted clinical, endoscopic, histological and/or radiologic criteria at least 6 months before the screening visit.
2. Has complex perianal fistula refractory to at least one of the following treatments: immunosuppressants or biologics (anti-tumor necrosis factor[TNF]s, anti-integrin, anti-interleukin [IL] 12/23). Fistula(s) refractory to therapy are defined in this study as follows: Immunosuppressants: Inadequate response after 3 months, based on clinical assessment, or more treatment with azathioprine, 6-mercaptopurine or methotrexate. Biologics: Inadequate response after 14 weeks (16 weeks for anti-IL 12/23), based on clinical assessment, or more standard treatment for induction and maintenance.
3. A complex perianal fistula(s) that meets one or more of the following criteria, modified from the American Gastroenterological Association (AGA) technical review: High intersphincteric, transsphincteric, extrasphincteric, or suprasphincteric as assessed by magnetic resonance imaging (MRI). Presence of 2-3 external openings (tracts) as assessed by clinical examination. Associated fluid collections as determined by MRI.
This study requires that the participant has complex perianal fistulas with a maximum of 2 internal openings and a maximum of 3 external openings, based on clinical assessment. Darvadstrocel treatment is targeted for fistulas that connect between internal and external openings. A central reading of a locally performed pelvic MRI will be performed to confirm the location of the fistula and potential associated perianal abscess(es). Fistulas must have been draining for at least 6 weeks before the screening visit. Participants with actively draining simple subcutaneous fistulas, at the time of the screening visit, are not allowed in this study.
4. Has inactive or mildly active luminal CD defined by meeting all of the following criteria:
a. Colonoscopy, flexible sigmoidoscopy or rectoscopy performed either at screening or within the 6 months before screening, demonstrating no rectal ulcers larger than 0.5 cm. A participant who has documented rectal ulcers larger than 0.5 cm within the 6 months before screening but has undergone subsequent treatment may be eligible if there are no rectal ulcers larger than 0.5 cm on a sigmoidoscopy or rectoscopy performed after treatment or at the time of screening.
b. The improvement of, or no worsening in stool frequency, sustained for 1 week or more, in the interval between the colonoscopy, flexible sigmoidoscopy or rectoscopy in inclusion criteria 4(a) and the screening visit.
c. No initiation or intensification of treatment with corticosteroids, immunosuppressants, or monoclonal antibody dose regimen between the colonoscopy, flexible sigmoidoscopy or rectoscopy in inclusion criteria 4(a) and the screening visit.
1. Has received any investigational compound within 12 weeks/84 days before screening.
2. Has received darvadstrocel/expanded adipose-derived mesenchymal stem cells(eASC) in a previous clinical study or as a therapeutic agent.
3. The participant weighs <10 kg at screening.
4. Has concomitant perianal fistula(s) with only internal or external opening(s).
5. Has concomitant internal fistula(s) such as ileo-vesical, rectovaginal or ileo-colonic fistula(s).
6. Has an abscess>2 cm, unless resolved in the preparation procedure.
7. Has rectal and/or anal stenosis, and/or active proctitis, which would restrict the surgical procedure.
8. The participant underwent surgery for the fistula other than drainage or seton placement.
9. Has diverting stomas.
10. Has ongoing systemic corticosteroid treatment or has been treated with systemic corticosteroids within 4 weeks before screening.
11. The participant requires new treatment with immunosuppressants/anti-TNF agents during the screening period.
12. The participant has known or suspected COVID-19 by the investigator within the past 2 months (additional testing may be performed at the discretion of the investigator). Positive antibody testing for COVID without other evidence of current or recent active infection does not exclude participation. Participants who were in screening at the time that COVID-19-related factors resulted in discontinuation may also be rescreened with approval of the sponsor or designee.
13. The participant requires surgery in the perianal region for reasons other than fistulas at the time of screening or foreseen either during the study and/or during the 24 weeks after treatment administration.
14. Has malignant tumor or a prior history of any malignant tumor, including any type of fistula carcinoma.
15. Has current or recent (within 3 months before the screening) history of abnormal, severe, progressive, uncontrolled hepatic, hematologic, gastrointestinal (except CD), endocrine, pulmonary, cardiac, neurological, psychiatric, or cerebral disease.
16. Has either congenital or acquired immunodeficiencies, including participants known to be HIV carriers or participants with, in the judgment of the investigator, are suspected to have monogenic inflammatory bowel disease.
17. Has previously received a bone marrow transplant.
18. Has a contraindication to MRI scan, or other planned study procedures.
19. Has a contraindication to the anesthetic procedure.
20. Had major surgery or severe trauma within 6 months before the screening visit.
4age old over
18age old not
Both
Crohn's Disease, Complex Perianal Fistula
Darvadstrocel (Cx601), 24 mL suspension of 120 million cells as a perilesional injection, once on Day 0.
1. Percentage of Participants who Achieve Combined Remission
Time Frame: Baseline and Week 24
Combined remission is defined as the closure of all treated external openings that were draining at baseline despite gentle finger compression, and absence of abscess (es) >2 cm (in at least 2 dimensions) of the treated perianal fistula(s) confirmed by central MRI assessment.
1. Percentage of Participants who Achieve Clinical Remission
Time Frame: Baseline and Weeks 24 and 52
Clinical remission is defined as the closure of all treated external openings that were draining at baseline despite gentle finger compression.
2. Percentage of Participants who Achieve Clinical Response
Time Frame: Baseline and Weeks 24 and 52
Clinical response is defined as closure of at least 50% of all treated external openings that were draining at baseline despite gentle finger compression.
3. Time to Clinical Remission
Time Frame: Baseline up to Week 52
Time to Clinical Remission is defined as the time in weeks from treatment start to first visit at which clinical remission is observed before Week 52; where clinical remission is said to occur if a clinical assessment shows closure of all treated external openings that were draining at baseline despite gentle finger compression.
4. Time to Clinical Response
Time Frame: Baseline up to Week 52
Time to clinical response defined as the time in weeks from treatment start to first visit at which clinical response is observed before Week 52; where clinical response is said to occur if a clinical assessment shows closure of at least 50% of all treated external openings that were draining at baseline despite gentle finger compression.
5. Percentage of Participants with Relapse in Participants with Combined Remission at Week 24
Time Frame: Baseline, Weeks 24 and 52
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 combined remission at Week 24.
6. Percentage of Participants with At Least One Adverse Event (AE)
Time Frame: From date of signing of informed consent form (ICF) up to Week 52
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.
7. Percentage of Participants with At Least One Serious Adverse Event (SAE)
Time Frame: From date of signing of ICF up to Week 52
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.
8. Percentage of Participants with At Least One Adverse Event of Special Interest (AESI)
Time Frame: From date of signing of ICF up to Week 52
An AESI include immunogenicity/alloimmune reactions, hypersensitivity, ectopic tissue formation, medication errors, tumorigenicity, transmission of infectious agents.
9. Percentage of Participants with Potentially Clinically Significant Vital Sign Values
Time Frame: Baseline up to Week 52
Vital signs will include body temperature (oral measurement), blood pressure (systolic and diastolic, resting more than 5 minutes), and heart rate (beats per minute).
10. Percentage of Participants with Potentially Clinically Significant Laboratory Values
Time Frame: Baseline up to Week 52
Laboratory parameters will include hematology, biochemistry, and urinalysis.
Takeda Pharmaceutical Company Limited
Juntendo University Hospital IRB
3-1-3, Hongo, Bunkyo-ku, Tokyo
+81-3-5802-1584
Approval
Feb. 19, 2021
Yes
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.
