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Study to Assess Efficacy and Safety of Cx601, Adult Allogeneic Expanded Adipose-derived Stem Cells (eASC) for the Treatment of Complex Perianal Fistula(s) in Participants With Crohn's Disease (CD)

Last Updated: 2024-09-19

Study Results

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Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

568 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-09-15

Study Completion Date

2023-07-26

Brief Summary

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The purpose of this study is to evaluate the combined remission of complex perianal fistulas, defined as the clinical assessment at Week 24 of closure of all treated external openings that were draining at baseline despite gentle finger compression, and absence of collections greater than (\>) 2 centimeter (cm) (in at least 2 dimensions) confirmed by blinded central magnetic resonance imaging (MRI) assessment at Week 24.

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Detailed Description

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This study is to assess the efficacy and safety of Cx601, eASC, for the treatment of complex perianal fistulas in participants with Crohn's disease.

The study will randomize approximately 554 participants.

* Cx601 eASCs intralesional injection
* Placebo - Cx601 placebo-matching eASCs intralesional injection

Study treatments will be allocated, on a 1:1 ratio, by central randomization through interactive web response system (IWRS). The study will follow an add-on design, participants receiving any ongoing concomitant medical treatment, at stable doses at the time of screening, for the CD will be allowed to continue it throughout the study.

The primary efficacy analysis, will be conducted at Week 24 timepoint. The double blind design will be maintained up to Week 52 (both participant and investigator) by a specific blinding for study treatment administration and for evaluating its efficacy.

This multicenter trial will be conducted globally across 150 centers. The overall time to participate in this study is approximately 5 years.

Conditions

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Crohn's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Placebo (saline) 24 milliliters (mL) was administered once by local injection.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Cx601 placebo-matching eASCs intralesional injection.

Cx601

Cx601 expanded adipose-derived stem cells (eASCs) 120 million cells (5 million cells per mL) was administered once by local injection.

Group Type EXPERIMENTAL

Cx601

Intervention Type DRUG

Cx601 eASCs intralesional injection.

Interventions

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Cx601

Cx601 eASCs intralesional injection.

Intervention Type DRUG

Placebo

Cx601 placebo-matching eASCs intralesional injection.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Signed informed consent.
2. Participants of either gender greater than or equal to (\>=) 18 years and less than or equal to (\<=) 75 years of age.
3. Participants with CD diagnosed at least 6 months prior to Screening visit in accordance with accepted clinical, endoscopic, histological and/or radiological criteria.
4. Presence of complex perianal fistula(s) with a maximum of 2 internal openings and a maximum of 3 external openings based on clinical assessment; a central reading of a locally performed contrast enhanced (gadolinium) pelvic MRI will be performed to confirm location of the fistula and potential associated perianal abscess(es). Fistula(s) must have been draining for at least 6 weeks prior to Screening visit. Actively draining simple subcutaneous fistula(s), at the time of Screening visit, are not allowed in this study. A complex perianal fistula is defined as a fistula that meets one or more of the following criteria :

* High inter-sphincteric, high trans-sphincteric, extra-sphincteric or suprasphincteric.
* Presence of \>=2 external openings.
* Associated perianal abscess(es). Note: Abscesses that are larger than 2 cm at least 2 dimensions on MRI must be confirmed to have been drained adequately by the surgeon during the preparation curettage in order to be eligible.
5. Clinically controlled, nonactive or mildly active CD, during the last six months prior to Screening visit with:

* A patient reported outcomes (PRO-2) score \<14 at Screening, AND
* A colonoscopy documenting the absence of ulcers larger than 0.5 cm in the colonic mucosa:

\- If colonoscopy data are not available within 6 months prior to Screening:
* A simple endoscopic score for Crohn's Disease (SES-CD) \<=6 with absence of rectal ulcers larger than 0.5 cm must be documented in a colonoscopy performed at Screening before randomization.

\- If colonoscopy data are available within 6 months prior to Screening, the following must be documented, otherwise a new colonoscopy (as above) will be mandatory:
* The absence of ulcers larger than 0.5 cm in the colonic mucosa AND
* the improvement or no worsening in abdominal pain and/or in the diarrhea, sustained for one week or more, since the last colonoscopy was performed in the clinical records until Screening visit.

AND

o No hemoglobin decrease \>=2.0 gram per deciliter (g/dL) or an unexplained rising C-reactive protein (CRP), \> 5.0 milligram per liter (mg/L) to a concentration above the referenced upper limit of normal (ULN) (unless the rise is due to a known process other than luminal Crohn's Disease), since the last colonoscopy was performed as compared to results during the Screening visit.

AND

o no initiation or intensification of treatment with corticosteroids, immunosuppressants or monoclonal antibodies (mAbs) dose regimen since the last endoscopy up to Screening visit.
6. Participants whose perianal fistulas were previously treated and have shown an inadequate response or a loss of response while they were receiving either an immunosuppressive agent or tumour necrosis factor (TNF)-alpha antagonist or vedolizumab or ustekinumab, or having documented intolerance to any of these treatments administered at least at approved or recommended doses during the minimum period mentioned:

* Immunosuppressive agents: at least 3 months treatment with azathioprine (2-3 milligram per kilogram per day \[mg/kg/day\]), 6-mercaptopurine (1-1.5 mg/kg/day), or subcutaneous/intramuscular methotrexate (25 mg/week) prior to Screening for the study.
* TNFalpha antagonists:
* Infliximab: at least 14 weeks treatment at the approved doses for induction and/or maintenance in Crohn´s disease prior to screening for the study. For induction: 1 intravenous dose of 5 milligram per kilogram (mg/kg) followed by the same dose 2 and 6 weeks after. For maintenance: 5-10 mg/kg intravenously every 8 weeks, or more frequently.
* Adalimumab: at least 14 weeks treatment at the approved doses for induction and/or maintenance in Crohn's disease prior to screening for the study. For induction: 1 subcutaneous dose of 160 milligram (mg), followed by 80 mg 2 weeks after. For maintenance: 40 mg subcutaneously every other week, or weekly.
* Certolizumab l: at least 14 weeks treatment at the approved doses for induction and/or maintenance in Crohn´s disease prior to screening for the study. For induction: 1 subcutaneous dose of 400 mg, followed by the same dose 2 and 4 weeks after. For maintenance: 400 mg subcutaneously every 2 to 4 weeks.
* Anti-integrin: at least 14 weeks treatment of the approved dose for induction and/or maintenance in Crohn´s disease prior to screening for the study. For induction: Vedolizumab 300 mg. For maintenance: Vedolizumab 300 mg every 4 to 8 weeks.
* Anti-interleukin (IL)-12/23: at least 16 weeks treatment of the approved dose in Crohn´s disease prior to screening for the study. For induction: Ustekinumab, approximately 6mg/kg intravenously initially then followed by 90 mg subcutaneously every 8 weeks.
7. Women of childbearing potential (WCBP) must have negative serum pregnancy test at screening (sensitive to 25 international units \[IU\] human chorionic gonadotropin \[hCG\]). Both WCBP or male participants participating in this study, with a WCBP as partner, must agree to use an adequate method of contraception during the entire duration of the study. An adequate method of contraception is defined as complete, non-periodic sexual abstinence (refraining from heterosexual intercourse), single-barrier method, vasectomy, adequate hormonal contraception (to have started at least 7 days prior to Screening visit), or an intra-uterine device (to have been in place for at least 2 months prior to Screening visit).

Exclusion Criteria

1. Concomitant rectovaginal or rectovesical fistula(s).
2. Participant naïve to prior specific medical treatment for complex perianal fistula(s) including immunosuppressant (IS) or anti-TNFs.
3. Presence of a perianal collection \>2 cm in at least two dimensions on the central reading MRI at Screening visit that was not adequately drained as confirmed by the surgeon during the preparation procedure (week -3 to day 0).
4. Severe rectal and/or anal stenosis and/or severe proctitis (defined as the presence of large \>0.5 cm ulcers in the rectum) that make impossible to follow the surgery procedure manual.
5. Participant with diverting stomas.
6. Active, uncontrolled infection requiring parenteral antibiotics.
7. Participant with ongoing systemic or rectal steroids for CD in the last 2 weeks prior to the Preparation visit.
8. Participants with major alteration on any of the following laboratory tests or increased risk for the surgical procedure:

* Serum creatinine levels \>1.5 times the ULN
* Total bilirubin \>1.5 ULN
* Aspartate Transaminase (AST)/ Alanine Transaminase (ALT) \>3 times ULN
* Hemoglobin \<10.0 g/dL
* Platelets \<75.0\*10\^9/L
* Albuminemia \<3.0 g/dL
9. Suspected or documented infectious enterocolitis within two weeks prior to Screening visit.
10. Any prior invasive malignancy diagnosed within the last 5 years prior to Screening visit. Participants with basal-cell carcinoma of the skin completely resected outside the perineal region can be included.
11. Current or recent (within 6 months prior to the Screening visit) history of severe, progressive, and/or uncontrolled hepatic, haematological, gastrointestinal (GI) (other than CD), renal, endocrine, pulmonary, cardiac, neurological or psychiatric disease that may result in participants increased risk from study participation and/or lack of compliance with study procedures.
12. Participants with primary sclerosing cholangitis.
13. Participants with known chronically active hepatopathy of any origin, including cirrhosis and participants with persistent positive 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 Screening.
14. Congenital or acquired immunodeficiencies, including participants known to be HIV carriers
15. Known allergies or hypersensitivity to penicillin or aminoglycosides; Dulbecco Modified Eagle's Medium (DMEM); bovine serum; local anaesthetics or gadolinium (MRI contrast).
16. Contraindication to MRI scan (example, due to the presence of pacemakers, hip replacements or severe claustrophobia).
17. Severe trauma within 6 months prior to Screening visit.
18. Pregnant or breastfeeding women.
19. Participants who do not wish to or cannot comply with study procedures.
20. Participants currently receiving, or having received any investigational drug within 3 months prior to Screening visit.
21. Participants previously treated with Cx601 or other allogeneic stem-cell therapy cannot be enrolled into this clinical study.
22. Any major surgery of the GI tract (including one or more segments of the colon or terminal ileum) within 6 months prior the screening or any minor surgery of the GI tract within 3 months prior to screening.
23. Participants who had local perianal surgery other than drainage for the fistula within 6 months prior to the Screening visit, or those who may need surgery in the perianal region for reasons other than fistulas at the time of inclusion in the study.
24. Contraindication to the anaesthetic procedure.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

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Scottsdale Mayo Clinic

Scottsdale, Arizona, United States

Site Status

UC San Diego Health Systems

La Jolla, California, United States

Site Status

University of Southern California (USC) Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

UC Irvine Medical Center - Chao Family Comprehensive Cancer

Orange, California, United States

Site Status

Inland Empire Liver Foundation

Rialto, California, United States

Site Status

Kaiser Permamente

San Francisco, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

Vallejo Hospital and Medical Offices

Vallejo, California, United States

Site Status

Cedar-Sinai Medical Center

West Hollywood, California, United States

Site Status

University of Colorado Hospital

Aurora, Colorado, United States

Site Status

Hartford Hospital - Gastroenterology

Farmington, Connecticut, United States

Site Status

Yale University School of Medicine

New Haven, Connecticut, United States

Site Status

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

Mayo Clinic - Gastroenterology

Jacksonville, Florida, United States

Site Status

University of Miami Hospital

Miami, Florida, United States

Site Status

Florida Hospital Orlando

Orlando, Florida, United States

Site Status

USF Health South Tampa Center for Advanced Healthcare

Tampa, Florida, United States

Site Status

Florida Hospital Tampa

Tampa, Florida, United States

Site Status

Cleveland Clinic Florida

Weston, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

The University of Chicago Medicine - Colon & Rectal Surgery

Chicago, Illinois, United States

Site Status

Carle Foundation Hospital

Urbana, Illinois, United States

Site Status

Indiana University - Colon and Rectal

Indianapolis, Indiana, United States

Site Status

University of Kansas Sxchool of Medicine

Kansas City, Kansas, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

Digestive Health Center of Louisiana

Baton Rouge, Louisiana, United States

Site Status

Colon and Rectal Surgery Associates

Metairie, Louisiana, United States

Site Status

University Medical Center - New Orleans

New Orleans, Louisiana, United States

Site Status

University of Maryland

Baltimore, Maryland, United States

Site Status

Johns Hopkins Medicine - The Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Massachussetts General Hospital

Boston, Massachusetts, United States

Site Status

Boston Medical Center

Boston, Massachusetts, United States

Site Status

Lahey Hospital & Medical Center

Burlington, Massachusetts, United States

Site Status

University of Massachusetts - colon & rectal surgery

Worcester, Massachusetts, United States

Site Status

Mayo Clinic College of Medicine - Division of Colon and Rectal Surgery - Division of Colon and Rectal Surgery

Rochester, Minnesota, United States

Site Status

Barnes-Jewish Hospital - Gastroenterology

St Louis, Missouri, United States

Site Status

University of Nevada School of Medicine

Las Vegas, Nevada, United States

Site Status

Dartmouth Hitchcock Medical Center - Cancer Center

Lebanon, New Hampshire, United States

Site Status

Morristown Medical Center - Gastroenterology

Morristown, New Jersey, United States

Site Status

Albany Medical Center

Albany, New York, United States

Site Status