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.
- Conditions
- Anal Passages/Openings with Crohn's DiseaseComplex Perianal Fistulas with Crohn's Disease10002112
- Registration Number
- NL-OMON55133
- Lead Sponsor
- Takeda
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 5
Subject eligibility is determined according to the following criteria prior to
entry into the study:
1. In the opinion of the investigator, the subject is capable of understanding
and complying with protocol requirements.
2. The subject, or when applicable, the subject's legally acceptable
representative, signs and dates a written, informed consent/pediatric assent
form and any required privacy authorization before the initiation of any study
procedures.
3. The subject is male or female aged 4 to <18 years at the time of informed
consent/pediatric assent.
4. The subject has a CD diagnosis based on accepted clinical, endoscopic,
histological and/or radiologic criteria at least 6 months before the screening
visit.
5. The subject has complex perianal fistula refractory to at least one of the
following treatments: immunosuppressants or biologics (anti-TNFs,
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-IL12/23),
based on clinical assessment, or more standard treatment for induction and
maintenance.
6. 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 MRI.
• Presence of 2 or 3 external openings (tracts) as assessed by clinical
examination.
• Associated fluid (abscess) collections as assessed by MRI.
This study requires that the subject 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. Subjects with actively
draining simple subcutaneous fistulas, at the time of the screening visit, are
not allowed in this study.
7. The subject 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 subject 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 7(a) and the screening visit.
c. No initiation or intensification of treatment with corticosteroids,
immunosuppressants, or mon
Any subject who meets any of the following criteria will not qualify for entry
into the study:
1. The subject has received any investigational compound within 12 weeks/84
days before screening.
2. The subject has received darvadstrocel/eASC in a previous clinical study or
as a therapeutic agent.
3. The subject is an immediate family member, study site employee, or is in a
dependent relationship with a study site employee who is involved in conduct of
this study (eg, spouse, parent, child, sibling), or may consent under duress.
4. The subject weighs <10 kg at screening.
5. The subject has, in the judgment of the investigator, clinically significant
abnormal hematological parameters of hemoglobin, hematocrit, or erythrocytes at
screening.
6. The subject has a history of hypersensitivity or allergies to darvadstrocel
or any of its excipients.
7. The subject takes or is required to take excluded medications.
8. The subject has concomitant perianal fistula(s) with only internal or
external opening(s).
9. The subject has concomitant internal fistula(s) such as ileo-vesical,
rectovaginal or ileo-colonic fistula(s).
10. The subject has an abscess >2 cm, unless resolved in the preparation
procedure.
11. The subject has rectal and/or anal stenosis, and/or active proctitis, which
would restrict the surgical procedure.
12. The subject underwent surgery for the fistula other than drainage or seton
placement.
13. The subject has diverting stomas.
14. The subject has ongoing systemic corticosteroid treatment or has been
treated with systemic corticosteroids within 4 weeks before screening.
15. The subject requires new treatment with immunosuppressants/anti-TNF agents
during the screening period.
16. The subject 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.
-Subjects 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.
17. The subject 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.
18. The subject has a serum creatinine >=2 × upper limit of normal (ULN).
19. The subject has hepatic impairment defined by both of the following
laboratory ranges:
a) Total bilirubin >=1.5 × ULN.
b) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >=2 × ULN.
20. The subject has known history of abuse of alcohol or other addictive
substances in the 6 months before screening.
21. The subject has malignant tumor or a prior history of any malignant tumor,
including any type of fistula carcinoma.
22. The subject 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.
23. The subject has either congenital or acquired
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Proportion of subjects who achieve combined remission at Week 24, where<br /><br>combined remission is defined as:<br /><br>a) The closure of all treated external openings that were draining at baseline<br /><br>despite gentle finger compression<br /><br>AND<br /><br>b) Absence of abscess(es) >2 cm (in at least 2 dimensions) of the treated<br /><br>perianal fistula(s) confirmed by central magnetic resonance imaging (MRI)<br /><br>assessment.</p><br>
- Secondary Outcome Measures
Name Time Method