A Study of Darvadstrocel in Adults With Crohn's Disease and Complex Perianal Fistula

Crohn's Disease Clinical Trial

— EMPIRE  

Official title:

Postauthorization Safety Study of the Long-Term Safety and Efficacy of Repeat Administration of Darvadstrocel in Patients With Crohn's Disease and Complex Perianal Fistula

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04118088
• Other study ID #: Alofisel-4001
• Secondary ID: EUPAS314392022-5
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: December 22, 2020
• Est. completion date: March 31, 2026

Study information

• Verified date: February 2024
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main aim is to check the long term side effects of a repeat treatment of darvadstrocel and to see if that treatment improves symptoms of Crohn's disease and complex perianal fistula. Participants will attend 8 clinic visits and will receive 1 treatment of darvadstrocel at the third visit. A magnetic resonance imaging (MRI) will be performed several times during the study.

Description:

The biological being tested in this study is called darvadstrocel (Alofisel). This study is examining the long-term safety and efficacy of a repeat dose of darvadstrocel in people who have Crohn's disease and complex perianal fistula.

The study will enroll approximately 50 patients. Participants will be assigned to one treatment group to receive:

• Darvadstrocel 120 million cells

All participants would be allowed to receive one repeat dose of darvadstrocel in the whole study. This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 3 years. Participants will make multiple visits to the clinic.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: March 31, 2026
• Est. primary completion date: March 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

2. The participant signs and dates a written, ICF and any required privacy authorization before the initiation of any study procedures.

3. The participant is male or female and aged 18 years or older.

4. The participant has complex perianal fistula(s) with a maximum of 2 internal openings and a maximum of 3 external openings based on clinical assessment and a reading of a locally-performed contrast enhanced (gadolinium) pelvic MRI. Fistula(s) must have been draining for at least 6 weeks prior to baseline visit. A complex perianal fistula is defined as a fistula that meets 1 or more of the following criteria:

1. High inter-sphincteric, high trans-sphincteric, extra-sphincteric or suprasphincteric.

2. Presence of =2 external openings.

3. Associated perianal abscess(es). Note: Abscesses that are larger than 2 cm in 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. The participant has already received treatment with darvadstrocel for a complex perianal fistula at least 6 months prior to baseline visit for retreatment, and their physician has planned a repeat treatment administration for the original tract (full remission not obtained or relapse of fistula draining) or for a new complex perianal fistula tract.

6. The participant has controlled or mildly active Crohn's disease (CD) (defined as patient reported outcomes measure derived from CDAI patient reported outcome score-2 [PRO-2] score <14).

7. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use barrier method of contraception (e.g. condom with or without spermicide) from signing of informed consent and until 1 year after repeat administration.

8. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use a highly effective/effective method of contraception from signing of informed consent and until 1 year after repeat administration.

Exclusion Criteria:

1. The participant has lack of clinical response to prior treatment with darvadstrocel, where clinical response is defined as closure of at least 50% of all treated external fistula openings that were draining at baseline despite gentle finger compression or in the case of a unique fistula, a partial closure of the fistula.

2. The participant has a history of hypersensitivity or allergies to darvadstrocel or related compounds.

3. The participant has a history of hypersensitivity or allergies to penicillin or to aminoglycosides; Dulbecco modified eagle medium; bovine serum; local anesthetics or gadolinium.

4. The participant is currently participating in a double-blind clinical study with darvadstrocel. Participants participating in the ongoing INSPIRE registry (Alofisel-5003) study would need to withdraw from that study in order to enroll in this study.

5. The participant is currently receiving or has received any other investigational medicinal product (IMP) within the last 3 months or at least 5 times the respective elimination half-life time, whichever is longer, before signing the ICF.

6. The participant 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.

a) Participants 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.

7. The participant has major alterations in any of the following laboratory tests:

1. Serum creatinine levels >1.5 times the upper limit of normal (ULN).

2. Total bilirubin >1.5 × ULN.

3. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3.0 × ULN.

4. Hemoglobin <10.0 grams per deciliter (g/dL).

5. Platelets <75.0 × 10^9 per liter (/L).

6. Albumin <3.0 g/dL.

8. The participant has an increased risk for a surgical procedure.

9. The participant has a known chronically active hepatopathy of any origin, including cirrhosis and participants with persistent positive hepatitis B surface antigen and quantitative hepatitis B virus polymerase chain reaction (PCR) or positive serology for hepatitis C virus (HCV) and quantitative HCV PCR within 6 months before the baseline visit.

10. If female, the participant is pregnant or breastfeeding, or intending to become pregnant before participating in this study, during the study, or intending to donate ova during such time period.

11. If male, the participant intends to donate sperm during this study.

12. The participant has a contraindication to MRI scan (e.g., due to the presence of pacemaker, hip replacement, severe claustrophobia, or renal insufficiency as defined by local clinical guidelines).

13. The participant has a contraindication to the anesthetic procedure.

14. The participant has severe rectal and/or anal stenosis that would make it impossible to follow the surgery procedure.

15. The participant has severe proctitis (rectal ulcers >0.5 cm) that would make it impossible to follow the surgery procedure.

16. The participant has any prior invasive malignancy diagnosed within the last 3 years before baseline visit. Participants with basal cell carcinoma of the skin completely resected outside the perineal region can be included.

17. The participant has a current or recent (within 6 months before the baseline visit) history of severe, progressive, and/or uncontrolled hepatic, hematologic, gastrointestinal (other than CD), renal, endocrine, pulmonary, cardiac, neurologic, or psychiatric disease that may result in participant's increased risk from study participation and/or lack of compliance with study procedures.

18. The participant has had major surgery of the gastrointestinal tract within 6 months before baseline or any minor surgery of the gastrointestinal tract 3 months before baseline.

19. The participant had local major perianal surgery, and/or treatment with darvadstrocel within 6 months before baseline. The abscess drainage, cleaning surgery, or seton placement are not considered as "local major surgery" in this protocol.

20. The participant does not wish to or cannot comply with study procedures.

Related Conditions & MeSH terms

• Complex Perianal Fistula
• Crohn Disease
• Crohn's Disease
• Fistula
• Rectal Fistula

Intervention

Biological:
• Darvadstrocel
Darvadstrocel suspension of human expanded adipose stem cells.

Locations

Country	Name	City	State
Austria	Akh Wien	Wien
Czechia	NH Hospital a.s.	Horovice
Czechia	ISCARE a.s.	Prague
France	CHU AMIENS PICARDIE Site SUD Hepato-Gastroenterology	AMIENS cedex 1	Picardie
France	CHRU de Lille - Hopital Claude Huriez - Gastroenterologie	Lille	Nord
France	CHU de Nice - Hopital de l'Archet II - Gastro-Enterologie, Hepatologi	Nice cedex 03	Alpes-Maritimes
France	Groupe Hospitalier Diaconesses Croix Saint Simon	Paris
France	Paris St. Joseph Hospital	Paris
France	Centre Hospitalier Lyon Sud - Gastroenterology	Pierre-Benite	Rhone
France	CHRU Hopital de Pontchaillou - Maladies De L'Appareil Digesti	Rennes	Ille-et-Vilaine
Germany	Charite - Campus Benjamin Franklin	Berlin
Germany	Krankenhaus Waldfriede	Berlin
Germany	Klinikum Dresden, University Hospital Dresden	Dresden	Sachsen
Germany	Stadtisches Klinikum Luneburg	Luneburg	Schleswig-Holstein
Israel	Hadassah Medical Organization, Hadassah Medical Center, Ein-Karem	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Rabin Medical Center, Beilinson Hospital	Petah Tikva
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Israel	Chaim sheba Medical Center	Tel Hashomer
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari de Bellvitge	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	H. Donostia	Donostia	San Sebastian
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Son Espases	Palma de Mallorca	Baleares
Spain	C.H.U. de Pontevedra	Pontevedra
Spain	Hospital Universitario Nuestra Senora de la Candelaria	Santa Cruz de Tenerife	Canarias
Spain	H.C.U. de Valencia	Valencia
Spain	Hospital Universitari i Politecnic La Fe	Valencia

Sponsors (2)

Lead Sponsor	Collaborator
Takeda	Takeda Development Center Americas, Inc.

Countries where clinical trial is conducted

Austria,  Czechia,  France,  Germany,  Israel,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with at Least 1 Treatment-Emergent Adverse Event (TEAE)	An AE is any untoward medical occurrence in a participant administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an AE with an onset that occurs after receiving study drug.	From signing of informed consent form (ICF ) up to 156 weeks post-repeat administration
Primary	Percentage of Participants with at Least 1 Treatment Emergent Serious Adverse Event (TESAE)	An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	From signing of ICF up to 156 weeks post-repeat administration
Primary	Number of Female Participants who are Pregnant	Female participants and/or female partners of male participants who become pregnant following treatment with the study product and report the pregnancy on a paper pregnancy report form immediately or within 24 hours of awareness are reported.	From administration of repeat dose up to 156 weeks post-repeat administration
Primary	Percentage of Participants with Treatment Emergent Adverse Event of Special Interest (TEAESI)	TEAESI includes immunogenicity/alloimmune reactions, hypersensitivity, transmission of infectious agents, tumorgenicity (applying to malignant tumors only), ectopic tissue formation, medication errors.	From signing of ICF up to 156 weeks post-repeat administration
Secondary	Percentage of Participants who Achieve Combined Remission of Perianal Fistula(s)	Combined remission is defined as the closure of all treated external openings that were draining at baseline, despite gentle finger compression and absence of collection(s) >2 centimeters (cm) (in at least 2 dimensions) of the treated perianal fistula(s) confirmed by central magnetic resonance imaging (MRI) assessment.	At Week 24 and at Week 156 post-repeat darvadstrocel administration
Secondary	Percentage of Participants who Achieve Clinical Remission	Clinical remission is defined as closure of all treated external fistula openings that were draining at baseline despite gentle finger compression.	At Weeks 6, 24, 52, 104, and 156 post-repeat darvadstrocel administration
Secondary	Percentage of Participants who Achieve Clinical Response	Clinical response is defined as closure of at least 50% of all treated external fistula openings that were draining at baseline despite gentle finger compression.	At Weeks 6, 24, 52, 104, and 156 post-repeat darvadstrocel administration
Secondary	Percentage of Participants with Relapse From Week 24 Combined Remission	Relapse is defined as reopening of any of the treated fistula(s) external openings with active drainage as clinically assessed that were in the combined remission at Week 24 or the development of a collection >2 cm (in at least 2 dimensions) of the treated perianal fistula(s) confirmed by centrally read MRI assessment.	From Week 24 to Week 156 post-repeat darvadstrocel administration
Secondary	Time to Relapse	Time to Relapse is defined as the time in days to reopening of any of the treated fistula(s) external openings with active drainage as clinically assessed, relative to Week 24.	From Week 24 to the Day of relapse post-repeat darvadstrocel administration
Secondary	Percentage of Participants with New Perianal Abscess in Treated Fistula		Up to Week 156 post-repeat darvadstrocel administration
Secondary	Change From Baseline in Score of Discharge and Pain Items of Perianal Disease Activity Index (PDAI) Score	The PDAI is a scoring system to evaluate the severity of perianal lesion associated with Crohn's disease. It includes the following 5 items: (a) discharge; (b) pain; (c) restriction of sexual activity; (d) type of perianal disease; and (e) degree of induration. Each item is graded on a 5-point scale ranging from no symptoms (score of 0) to severe symptoms (score of 4) and total range of score is from 0 to 20. Higher score means more severe disease.	Baseline to Weeks 6, 24, 52, 104, and 156 post-repeat darvadstrocel administration