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

NCT03706456 | Completed Phase 3 Results

• 4 other identifiers: Darvadstrocel-3002U1111-1218-8079JapicCTI-184145Alofisel-3002
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

Complex Perianal Fistulas in Adult Participants With Crohn's Disease

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (24)

• Percentage of Participants With Clinical Remission of Perianal Fistulising CD at Week 24

  Week 24

• Percentage of Participants With Response of Perianal Fistulising CD at Week 24

  Week 24

• Time to Clinical Remission of Perianal Fistulising CD by Week 24

  Up to Week 24

• Time to Response of Perianal Fistulising CD by Week 24

  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

  Week 24

Study Arms (1)

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.

Biological: Darvadstrocel

Interventions

Darvadstrocel BIOLOGICAL

Darvadstrocel cell suspension for intralesional injection.

Also known as: Cx601

Darvadstrocel 24 mL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• The participant who has concomitant rectovaginal or rectovesical fistulas.
• The participant who has \>2 internal openings of \>3 external openings.
• The participant who is naïve to protocol required treatment for complex perianal fistulising Crohn's disease (ie, antibiotics, immunosuppressants or biologics).
• The participant who has an abscess or collections \>2 cm.
• The participant who has rectal and/or anal stenosis and/or active proctitis, which would restrict the surgical procedure.
• The participant who underwent surgery other than drainage or seton placement for the to be treated fistula.
• The participant who has diverting stomas.
• The participant who was treated with systemic steroids in the 4 weeks prior to study product administration.
• The participant receiving cytapheresis therapy.
• The participant who requires new treatment with immunosuppressants/biologics/non-tapered systematic steroids during the screening period.
• 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).
• 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.
• The participant who has history of abuse of alcohol or other addictive substances in the 6 months prior to the screening period.
• The participant who has malignant tumour or who has a history of malignant tumour, including any type of fistula carcinoma.

Sponsors & Collaborators

• Takeda: lead

Study Sites (11)

Ieda Hospital

Toyota, Aichi-ken, Japan

Location

Fukuoka University Chikushi Hospital

Chikushino-shi, Fukuoka, Japan

Location

Sapporo Higashi Tokushukai Hospital

Sapporo, Hokkaido, Japan

Location

Hyogo College of Medicine

Nishinomiya, Hyōgo, Japan

Location

Yokohama Municipal Citizen's Hospital

Yokohama, Kanagawa, Japan

Location

Mie University Hospital

Tsu, Mie-ken, Japan

Location

Tohoku Rosai Hospital

Sendai, Miyagi, Japan

Location

Tohoku University Hospital

Sendai, Miyagi, Japan

Location

Osaka University Hospital

Suita, Osaka, Japan

Location

JCHO Tokyo Yamate Medical Center

Shinjuku, Tokyo, Japan

Location

Coloproctology Center Takano Hospital

Kumamoto, Japan

Location

Related Publications (1)

• 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.

  PMID: 36149832 DERIVED

Related Links

• To obtain more information on the study, click here/on this link

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2018
• First Posted: October 16, 2018
• Study Start: March 6, 2019
• Primary Completion: July 20, 2020
• Study Completion: February 10, 2023
• Last Updated: June 10, 2024
• Results First Posted: October 7, 2021

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: 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.

Locations

JP (11)