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

• Register: ClinicalTrials.gov
• Last refreshed on: 18 June 2024
• Main ID: NCT03706456
• Date of registration: 11/10/2018
• Prospective Registration: Yes
• Primary sponsor: Takeda
• Public title: Phase 3 Study of Cx601 in Participants With Complex Perianal Fistulising Crohn's Disease
• Scientific title: A Phase 3, Multicenter, Open-Label, Uncontrolled Study to Evaluate the Efficacy and Safety of Cx601 in the Treatment of Complex Perianal Fistulas in Adult Patients With Crohn's Disease
• Date of first enrolment: March 6, 2019
• Target sample size: 22
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03706456
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Japan

Contacts

• Name: Study Director
• Affiliation: Takeda

Key inclusion & exclusion criteria

Inclusion Criteria:

1. In the opinion of the investigator, the participant is capable of understanding and
complying with the protocol requirements.

2. 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.

3. 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).

4. The participant is either a male or female outpatient, aged 18 years or older at the
time of signing the informed consent form.

5. 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.

6. 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:

- High (ie, above the dentate line) inter-sphincteric or trans-sphincteric
fistula, extrasphincteric fistula, or supra-sphincteric fistula.

- Presence of >=2 external openings (tracts).

- Associated fluid collections.

7. 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;

- Antibiotics (ciprofloxacin or metronidazole): 1 or more month treatment.

- Immunosuppressants (azathioprine, 6-mercaptopurine or methotrexate): 3 or more
months treatment.

- Biologics (anti-tumor necrosis factors [TNFs], anti-integrin or
anti-interleukin [IL]-12/23): 14 or more weeks (16 or more weeks for
anti-IL-12/23) standard treatment for induction or maintenance.

8. 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.

9. 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:

1. The participant whose CDAI is >220 at any time between Visit 1 and Visit 2, or who
has active Crohn's disease requiring a new of escalating immediate therapy.

2. The participant who has concomitant rectovaginal or rectovesical fistulas.

3. The participant who has >2 internal openings of >3 external openings.

4. The participant who is naïve to protocol required treatment for complex perianal
fistulising Crohn's disease (ie, antibiotics, immunosuppressants or biologics).

5. The participant who has an abscess or collections >2 cm.

6. The participant who has rectal and/or anal stenosis and/or active proctitis, which
would restrict the surgical procedure.

7. The participant who underwent surgery other than drainage or seton placement for the
to be treated fistula.

8. The participant who has diverting stomas.

9. The participant who was treated with systemic steroids in the 4 weeks prior to study
product administration.

10. The participant receiving cytapheresis therapy.

11. The participant who requires new treatment with
immunosuppressants/biologics/non-tapered systematic steroids during the screening
period.

12. The participant who has renal impairment defined by creatinine clearance below 60
mL/minute calculated using Cockcroft-Gault formula or by serum creatinine >=1.5 ×
upper limit of normal (ULN).

13. The participant who has hepatic impairment defined by both total bilirubin >=1.5 ×
ULN, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >=2.5 ×
ULN.

14. The participant who has history of abuse of alcohol or other addictive substances in
the 6 months prior to the screening period.

15. The participant who has malignant tumour or who has a history of malignant tumour,
including any type of fistula carcinoma.

16. The participant who has abnormal, severe, progressive, uncontrolled hepatic,
hematological, gastrointestinal (except Crohn's disease), endocrine, pulmonary,
cardiac, neurological, psychiatric, or cerebral disease, or the participant who
developed any of the above diseases within 3 months prior to the screening period.

17. The participant who has congenital or acquired immunodeficiency, including
participants known to be Human Immunodeficiency Virus (HIV) carriers.

18. The participant who has clinically significant chronically active hepatopathy of any
origin, including hepatic cirrhosis, and participants who is persistent positive for
hepatitis B virus (HBV) surface antigen (HBsAg) and quantitative HBV polymerase
chain reaction (PCR), or positive serology for hepatitis C virus (HCV) and
quantitative HCV-PCR within 6 months prior to the screening period.

19. The participant who has known allergies or hypersensitivity to antibiotics
(including but not limited to penicillin, streptomycin, gentamicin,
aminoglycosides), Human Serum Albumin (HSA), bovine-derived materials, local
anesthetics or gadolinium (MRI contrast agent).

20. The participant for whom MRI scan is contraindicated (eg, due to the presence of a
pacemaker, a history of hip replacements, or severe claustrophobia).

21. The participant who has major surgery (eg, surgery under general anesthesia,
laparotomy, thoracotomy, craniotomy) or severe trauma within 6 months prior to the
screening period.

22. The female participant who is pregnant, or is lactating.

23. The participant who has received any investigational drug within 12 weeks (84 days)
prior to the screening.

24. The participant who has received expanded allogeneic adipose-derived stem cells
(eASC) in a previous clinical study or as a therapeutic agent.

25. The participant who needs perianal surgery other than fistulas preparation required
by the protocol during the screening, or the participant who will receive a perianal
surgery within 24 weeks after


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Complex Perianal Fistulas in Adult Participants With Crohn's Disease

Intervention(s)

Biological: Darvadstrocel

Primary Outcome(s)

Percentage of Participants With Combined Remission of Perianal Fistulising Crohn's Disease (CD) at Week 24 [Time Frame: Week 24]

Secondary Outcome(s)

Percentage of Participants With Relapse of Perianal Fistulising CD at Week 24 in Participants With Clinical Remission at a Previous Visit [Time Frame: Week 24]

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

Change From Baseline in PDAI: Pain Sub-Score at Week 24 [Time Frame: Baseline and Week 24]

Percentage of Participants With Clinical Remission of Perianal Fistulising CD at Week 24 [Time Frame: Week 24]

Percentage of Participants With Relapse of Perianal Fistulising CD at Week 52 in Participants With Combined Remission at Week 24 [Time Frame: Week 52]

Time to Combined Remission of Perianal Fistulising CD by Week 52 [Time Frame: Up to Week 52]

Time to Response of Perianal Fistulising CD by Week 24 [Time Frame: Up to Week 24]

Change From Baseline in PDAI: Discharge Sub-Score at Week 52 [Time Frame: Baseline and Week 52]

Change From Baseline in PDAI: Pain Sub-Score at Week 52 [Time Frame: Baseline and Week 52]

Change From Baseline in PDAI: Discharge Sub-Score at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in Van Assche Total Score at Week 52 [Time Frame: Baseline and Week 52]

Percentage of Participants With Response of Perianal Fistulising CD at Week 24 [Time Frame: Week 24]

Time to Clinical Remission of Perianal Fistulising CD by Week 24 [Time Frame: Up to Week 24]

Time to Relapse of Perianal Fistulising CD by Week 24 in Participants With Clinical Remission at a Previous Visit [Time Frame: Up to Week 24]

Change From Baseline in Perianal Disease Activity Index (PDAI): Total Score at Week 24 [Time Frame: Baseline and Week 24]

Time to Clinical Remission of Perianal Fistulising CD by Week 52 [Time Frame: Up to Week 52]

Change From Baseline in Van Assche Score at Week 24 [Time Frame: Baseline and Week 24]

Percentage of Participants With Clinical Remission of Perianal Fistulising CD at Week 52 [Time Frame: Week 52]

Percentage of Participants With Combined Remission of Perianal Fistulising CD at Week 52 [Time Frame: Week 52]

Time to Relapse of Perianal Fistulising CD by Week 52 in Participants With Combined Remission at Week 24 [Time Frame: Up to Week 52]

Time to Response of Perianal Fistulising CD by Week 52 [Time Frame: Up to Week 52]

Change From Baseline in CDAI: Total Score at Week 52 [Time Frame: Baseline and Week 52]

Change From Baseline in PDAI: Total Score at Week 52 [Time Frame: Baseline and Week 52]

Percentage of Participants With Response of Perianal Fistulising CD at Week 52 [Time Frame: Week 52]

Secondary ID(s)

JapicCTI-184145

U1111-1218-8079

Darvadstrocel-3002

Alofisel-3002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 07/10/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03706456