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Long-term Follow-up Study With Darvadstrocel in the Treatment of Complex Perianal Fistula

Phase 3
Completed
Conditions
Complex Perianal Fistula
Crohn's Disease
Interventions
Registration Number
NCT04075825
Lead Sponsor
Takeda
Brief Summary

The main aim is to follow-up on long term side effect and symptom improvement of Darvadstrocel in the treatment of complex perianal fistula in adults. Participants will not receive any drug in this study.

Detailed Description

The drug being tested in this study is called darvadstrocel (Cx601). Darvadstrocel is being tested to treat people who have complex perianal fistula in CD. This study will look at the long-term safety and efficacy of darvadstrocel in the treatment of complex perianal fistula in CD.

The study will enroll approximately 150 patients. Participants who received darvadstrocel or placebo in study ADMIRE-CD II (Cx601-0303, NCT03279081) and who have completed the 52 weeks of the study will be enrolled in this long-term extension study.

This multi-center study will be conducted worldwide. The overall time to participate in this study is 104 weeks (in addition to the 52 weeks on ADMIRE-CD II study). Participants will make multiple visits to the clinic and will be contacted by telephone every 3 months for a follow-up assessment. After unblinding of the ADMIRE-CD II study, the LTE study will be conducted as an open-label study. Participants will remain in the treatment group assigned in the ADMIRE-CD II study.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
150
Inclusion Criteria
  1. Has participated in and completed the ADMIRE-CD II (NCT03279081) study (i.e., did not discontinue).
Exclusion Criteria
  1. Has been more than 3 months since the participant completed the ADMIRE-CD II study.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboParticipants who received darvadstrocel placebo-matching expanded adipose-derived stem cells (eASCs) intralesional injection previously in the ADMIRE-CD II study were observed for efficacy and safety. No drug was administered in this study.
DarvadstrocelDarvadstrocelParticipants who received a single dose of darvadstrocel, 120 million cells, intralesionally previously in the ADMIRE-CD II study were observed for efficacy and safety. No drug was administered in this study.
Primary Outcome Measures
NameTimeMethod
Number of Participants With Treatment Emergent Adverse Events (TEAEs)Baseline (Week 0) up to Week 104 of this study (Week 52 up to Week 156 in relation to ADMIRE-CD II)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered an investigational medicinal product; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with a study intervention or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the study intervention or medicinal product.

Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs)Baseline (Week 0) up to Week 104 of this study (Week 52 up to Week 156 in relation to ADMIRE-CD II)

TEAE is defined as: any adverse event emerging/manifesting at or after the initiation of treatment with a study intervention/medicinal product or any existing event that worsens in either intensity/frequency following exposure to the study intervention/medicinal product. Serious adverse event (SAE) is an untoward medical occurrence, significant hazard, contraindication, side effect/precaution that at any dose: results in death, is life-threatening, required in-patient hospitalization/prolongation of existing hospitalization, results in persistent/significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Number of Participants With Specific Adverse Events of Special Interest (AESIs)Baseline (Week 0) up to Week 104 of this study (Week 52 up to Week 156 in relation to ADMIRE-CD II)

AESIs are AEs that are not solicited local or systemic AEs, they are predefined AEs that require close monitoring and prompt reporting to the sponsor. Protocol pre-specified AESIs included immunogenicity/allo-immunoreactions, tumorigenicity, ectopic tissue formation and fistula/abscess. In addition, ad hoc AESIs of anaphylactic reaction, hypersensitivity, and malignancy.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants Who Achieve Clinical Remission at Weeks 104 and 156 (After IMP Administration in ADMIRE-CD II Study)At Weeks 52 and 104 of this study (Weeks 104 and 156 in relation to ADMIRE-CD II, respectively)

Clinical remission is defined as closure of all treated external fistula openings that were draining at baseline of ADMIRE-CD II despite gentle finger compression. Percentages were rounded off to the nearest second decimal place.

Percentage of Participants Who Achieve Clinical Response at Weeks 104 and 156 (After IMP Administration in ADMIRE-CD II Study)At Weeks 52 and 104 of this study (Weeks 104 and 156 in relation to ADMIRE-CD II, respectively)

Clinical response is defined as closure of at least 50% of all treated external fistula openings that were draining at baseline of ADMIRE-CD II despite gentle finger compression. Percentages were rounded off to the nearest second decimal place.

Percentage of Participants With Relapse at Week 156 After Achieving Combined Remission at Week 52 of ADMIRE-CD IIAt Week 104 of this study (Week 156 in relation to ADMIRE-CD II)

Relapse is defined as participants who were in combined remission at Week 52 of ADMIRE-CD II and who have either reopening of any of the treated fistula(s) external openings with active drainage as clinically assessed or, the development of a perianal fluid collection \>2 cm of the treated perianal fistulas confirmed by centrally read magnetic resonance imaging (MRI) assessment. Combined remission at Week 52 was defined as clinically assessed closure of all treated external openings that were draining at baseline of ADMIRE-CD II, despite gentle finger compression, and absence of collection(s) \>2 cm (in at least 2 dimensions) of the treated perianal fistula(s) confirmed by blinded central MRI assessment. Percentages were rounded off to the nearest second decimal place.

Percentage of Participants Who Achieve Combined Remission at Week 156 (After IMP Administration in ADMIRE-CD II Study)At Week 104 of this study (Week 156 in relation to ADMIRE-CD II)

Combined remission of complex perianal fistula(s) is defined as the clinical assessment of closure of all treated external openings that were draining at baseline of ADMIRE-CD II, despite gentle finger compression, and absence of collection(s) \>2 cm (in at least 2 dimensions) of the treated perianal fistula(s) confirmed by centrally read blinded MRI assessment. Percentages were rounded off to the nearest second decimal place.

Percentage of Participants With New Anal Abscess in Treated Fistula at Week 156At Week 104 of this study (Week 156 in relation to ADMIRE-CD II)

Percentages were rounded off to the nearest second decimal place.

Change From Baseline of ADMIRE-CD II in Scores of Discharge Items of Perianal Disease Activity Index (PDAI) Score at Weeks 104 and 156From Baseline of ADMIRE-CD II up to Weeks 52 and 104 of this study (From Baseline up to Weeks 104 and 156 in relation to ADMIRE-CD II, respectively)

The PDAI is a scoring system to evaluate the severity of perianal CD. From the 5-item instrument, only 'discharge' was used for this outcome measure. Each category is graded on a 5-point Likert scale ranging from no symptoms (score of 0) to severe symptoms (score of 4); a higher score indicates more severe disease.

Change From Baseline of ADMIRE-CD II in Scores of Pain Items of Perianal Disease Activity Index (PDAI) Score at Weeks 104 and 156From Baseline of ADMIRE-CD II up to Weeks 52 and 104 of this study (From Baseline up to Weeks 104 and 156 in relation to ADMIRE-CD II, respectively)

The PDAI is a scoring system to evaluate the severity of perianal CD. From the 5-item instrument, only 'pain' was used for this outcome measure. Each category is graded on a 5-point Likert scale ranging from no symptoms (score of 0) to severe symptoms (score of 4); a higher score indicates more severe disease.

Trial Locations

Locations (58)

University of California San Francisco

🇺🇸

San Francisco, California, United States

Cedar-Sinai Medical Center

🇺🇸

West Hollywood, California, United States

Yale University School of Medicine

🇺🇸

New Haven, Connecticut, United States

Cleveland Clinic Florida

🇺🇸

Fort Lauderdale, Florida, United States

University of Miami Hospital

🇺🇸

Miami, Florida, United States

USF Health South Tampa Center for Advanced Healthcare

🇺🇸

Tampa, Florida, United States

AdventHealth Tampa

🇺🇸

Tampa, Florida, United States

Indiana University - Colon and Rectal

🇺🇸

Indianapolis, Indiana, United States

University of Kansas Medical Center (KUMC) - University of Kansas Liver Center - Hepatology Clinic

🇺🇸

Kansas City, Kansas, United States

Johns Hopkins School of Medicine

🇺🇸

Baltimore, Maryland, United States

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University of California San Francisco
🇺🇸San Francisco, California, United States

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