USTekinumab in Fistulising Perianal Crohn's Disease (USTAP) (USTAP)

January 18, 2024 updated by: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

USTekinumab in Fistulising Perianal Crohn's Disease (CD): The USTAP CD Study

Phase IV

Trial design : Multicentre, randomized, double-blind, placebo-controlled study

Population : Moderate to severe Crohn's disease with at least one active perianal fistula track

Investigational treatment : Group 1: Ustekinumab (UST) IntraVenous (IV) induction (6mg/kg) followed by UST SubCutaneous (SC) 90mg every 8 weeks. Group 2: Placebo IV followed by Placebo SC The trial duration for each patient will be 48 weeks.

Trial objective : To evaluate the efficacy and safety of ustekinumab in fistulizing perianal Crohn's disease.

Number of patients : A total of 146 patients will be included in 20 sites in France

Trial duration : First patient in: Q3 2020 - Last patient first visit: Q3 2022 Last patient last visit: Q3 2023

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Main endpoint:

The primary endpoint will be combined remission at week 12 defined as:

  • 100% of the fistula tracts without any drainage by the external openings (occurring spontaneously or after gentle finger compression) And
  • absence of collections >2 cm of the treated perianal fistulas confirmed by masked central MRI Patient requiring UST optimization will be considered in failure but will be followed until week 48

Secondary endpoints:

Definition

  • Clinical remission: 100% of the fistula tracts without any drainage by the external openings (i.e, absence of any drainage by all fistula openings occurring spontaneously or after gentle finger compression)
  • Clinical response (closure of at least 50% of all treated external openings that were draining at baseline)
  • Radiological remission: absence of collections >2 cm of the treated perianal fistulas confirmed by masked central MRI
  • Combined clinical and radiological remission at week 24 and 48.
  • Clinical remission (i.e, absence of any drainage by all fistula openings occurring spontaneously or after gentle finger compression) at week 12, 24 and 48
  • Absence of collections >2 cm of the treated perianal fistulas confirmed by masked central MRI at week 12, 24 and 48
  • Evaluation of the magnetic resonance novel index for fistula imaging in CD at week 12, 24 and 48
  • Clinical response (closure of at least 50% of all treated external openings that were draining at baseline) at week 12, 24 and 48
  • Combined clinical response and radiological remission at week 48
  • Perineal Disease Activity Index (PDAI), Crohn Disease Activity Index (CDAI) at week 12, 24 and 48
  • Quality of life will be assessed with the Inflammatory Bowel Disease questionnaire (IBDQ) scores at week 24 and 48
  • Correlation between response and remission and UST trough levels and antidrug (UST) antibodies at week 12, 24, 48
  • Clinical response of UST optimization at week 48 (closure of at least 50% of all treated external openings that were draining at week 12)
  • Clinical response at week 48 of UST introduction at W12 (closure of at least 50% of all treated external

Study Type

Interventional

Enrollment (Estimated)

146

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Amiens, France, 80054
      • Besançon, France
        • Not yet recruiting
        • CHU Besançon
        • Contact:
          • Lucine VUITTON
        • Contact:
        • Principal Investigator:
          • Lucine VUITTON, MD
      • Clermont-Ferrand, France, 63003
      • Clichy, France, 92110
        • Not yet recruiting
        • APHP- Hopital Beaujon
        • Contact:
        • Principal Investigator:
          • Yoram BOUHNIK, MD
      • Colombes, France, 92700
        • Not yet recruiting
        • Hopital Louis Mourier
        • Contact:
        • Principal Investigator:
          • Benoit COFFIN, MD PhD
      • Le Kremlin Bicêtre, France, 94270
        • Not yet recruiting
        • Hopital Kremlin Bicetre
        • Contact:
        • Principal Investigator:
          • Franck CARBONNEL, MD PhD
      • Lille, France, 59037
      • Montpellier, France, 34295
        • Not yet recruiting
        • CHU Montpellier - St Eloi
        • Contact:
        • Principal Investigator:
          • Romain Altwegg, MD
      • Nantes, France, 44093
        • Not yet recruiting
        • Hôpital Hotel Dieu
        • Contact:
        • Principal Investigator:
          • Arnaud BOUREILLE, MD PhD
      • Nice, France, 62002
        • Not yet recruiting
        • CHU Nice- Hopital l'Archet
        • Contact:
        • Principal Investigator:
          • Xavier HEBUTERNE, MD PhD
      • Nîmes, France, 30029
        • Recruiting
        • CHU Nîmes - Hôpital Universitaire Caremeau
        • Principal Investigator:
          • Ludovic CAILLO, MD
        • Contact:
      • Paris, France, 75010
        • Not yet recruiting
        • Hopital St Louis
        • Contact:
        • Principal Investigator:
          • Matthieu ALLEZ, MD PhD
        • Sub-Investigator:
          • Joëlle BONNET, MD
      • Paris, France, 75012
        • Not yet recruiting
        • Hopital Saint-Antoine
        • Contact:
        • Principal Investigator:
          • Philippe SEKSIK, MD PhD
      • Paris, France, 75018
      • Pierre-Bénite, France, 69495
        • Recruiting
        • CHU LYON- Hopital Lyon Sud
        • Contact:
        • Principal Investigator:
          • Stéphane NANCEY, MD
      • Roubaix, France, 59056
        • Not yet recruiting
        • CHU Roubaix
        • Contact:
        • Principal Investigator:
          • Nicolas DUVEAUX, MD
      • Saint-Priest-en-Jarez, France, 42270
        • Recruiting
        • CHU Saint-Etienne
        • Contact:
        • Principal Investigator:
          • Xavier ROBLIN, MD PhD
      • Tours, France, 37044
        • Not yet recruiting
        • CHU DE TOURS - Hopital Trousseau
        • Contact:
        • Principal Investigator:
          • Laurence PICON, MD
      • Vandœuvre-lès-Nancy, France, 54500
        • Recruiting
        • CHU Nancy - Hôpital de Brabois
        • Contact:
        • Principal Investigator:
          • Laurent PEYRIN-BIROULET, MD PhD
    • Bretagne
      • Rennes, Bretagne, France, 35033
        • Not yet recruiting
        • CHU Rennes
        • Sub-Investigator:
          • Marie DEWITTE, MD
        • Contact:
        • Principal Investigator:
          • Guillaume BOUGUEN, MD PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥18 years
  • Adults with moderate to severe Crohn's disease for at least six months
  • Patients with at least one active perianal fistula track (between the anus or low rectum and the perineum or vulva) confirmed by MRI within the previous 12 weeks
  • Patients either naïve to anti-TNF therapy (50%) or refractory to anti-TNF therapy (50%).

  • If female, subject is either not of child bearing potential, defined as post-menopausal for at least1 year, surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or is of childbearing potential and practicing one of the following methods of birth control during the study and for 150 days after the last dose:

    • Condoms, sponge and foam, jellies with diaphragm or intrauterine device (IUD). IUDs may fail during azathioprine treatment. Alternative or additional contraceptive measures are advised, if azathioprine is initiated
    • Oral or parenteral contraceptives for 3 months prior to study drug administration
    • A vasectomized partner
  • Male subjects must agree to use an acceptable form of birth control, listed above at the start of azathioprine administration and for 90 days after last dose of azathioprine. Males should also commit to inform his partner(s) about it and to report any pregnancy to the investigator.
  • If female, subject is not breast-feeding throughout the study and for 150 days after last dose.
  • Subjects or his/her legal representative have voluntarily signed and dated an informed consent approved by and compliant with the requirements of this study protocol which has been approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
  • Adequate cardiac, renal and hepatic function as determined by the Principal Investigator and demonstrated by Screening laboratory evaluations, questionnaires and physical examination results that do not indicate an abnormal clinical condition which would place the subject at undue risk and thus preclude subject participation in the study
  • Subject with a negative tuberculosis (TB) Screening Assessment [(including a Purified Protein Derivative (PPD) test < 5 mm and/or negative QuantiFERON-TB Gold test or equivalent and negative Chest X-Ray (CXR) (PA and lateral view)] at screening

Exclusion Criteria:

  • Absence of written consent. People unable to give their consent (because of their physical or mental state)
  • Pregnancy or breastfeeding
  • Rectovaginal fistulas
  • Rectal and/or anal stenosis
  • Diverting stomas
  • Abscess or collections >2 cm which are not properly drained ((i.e not drained at least 3 weeks before baseline and adequately treated provided that there is no anticipated need for any further surgery)
  • History of colectomy.
  • History of colonic mucosal dysplasia or adenomatous colonic polyps that are not removed.
  • Screening stool trial positive for enteric pathogens or Clostridium difficile toxin. History of ongoing, chronic or recurrent infectious disease
  • Positive HIV, Hepatitis B Virus (HBV),Hepatitis C Virus (HCV)
  • Severe infection, chronic infection, history of recurrent infections, active infection including TB
  • Malignancies or history of malignancies
  • History of congestive heart failure (NYHA: Grade III and IV), demyelinating disease, current signs or history of severe/ progressive/uncontrolled renal, hepatic, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease, or systemic lupus erythematosus (SLE).
  • History of transplanted organ, lymphoproliferative disease, any known malignancy
  • Previous allergy immunotherapy for anaphylaxis, hypersensitivity to ustekinumab or to any excipients, or metronidazole or ciprofloxacin
  • Previous use of a biologic agent targeting Interleukin 12 (IL12) and/or Interleukin 23 (IL 23), including but not limited to ustekinumab
  • Oral corticosteroids at a dose > 40 mg prednisone or its equivalent per day at inclusion (oral steroids should be at stable dose at least 7 days before inclusion)
  • Any current or previous use of the following within 8 weeks before the first trial agent injection : cyclosporine, tacrolimus, anti-TNF biologic agents or other agents intended to suppress or eliminate Tumor Necrosing Factor (TNF), and other biologics, including anti-integrin antibodies (approved or investigational), Janus Kinase (JAK) inhibitors (approved or investigational), or any current or previous use of an investigational agent
  • Non-autologous stem cell therapy or biologic agents that deplete B or T cells <12 months prior to baseline
  • Current or recent (less than 4 weeks) vaccination with attenuated live vaccines
  • Patients using a prohibited medication
  • Patients participating in another trial or being in a follow-up period for another trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1 Ustekinumab
Intravenous induction (6mg/kg) followed by Ustekinumab subcutaneous 90mg every 8 weeks
Drug: Ustekinumab
Intravenous induction (6mg/kg) followed by Ustekinumab subcutaneous 90mg every 8 weeks
Other Names:
  • Stelara
Placebo Comparator: Group 2 Placebo
Placebo intravenous followed by Placebo subcutaneous every 8 weeks
Drug: Placebo
Placebo intravenous followed by Placebo subcutaneous every 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Combined clinical and radiological remission
Time Frame: Week 12

Number of participants with 100% of the fistula tracts without any drainage by the external openings (occurring spontaneously or after gentle finger compression)

- Number of participants with absence of collections >2 cm of the treated perianal fistulas confirmed by masked central MRI.
Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Combined clinical and radiological remission
Time Frame: week 24 and week 48

Number of participants with 100% of the fistula tracts without any drainage by the external openings (occurring spontaneously or after gentle finger compression)

- Number of participants with absence of collections >2 cm of the treated perianal fistulas confirmed by masked central MRI.
week 24 and week 48
Clinical response
Time Frame: week 12, week 24 and week 48
Number of participants with closure of at least 50% of all treated external openings that were draining at baseline
week 12, week 24 and week 48
MAGNIFI-CD26
Time Frame: week 12, week 24 and week 48
Evaluation of the magnetic resonance novel index for fistula imaging in CD (MAGNIFI-CD26)
week 12, week 24 and week 48
PDAI
Time Frame: week 12, week 24 and week 48
Perineal Disease Activity Index
week 12, week 24 and week 48
IBDQ scores
Time Frame: week 24 and week 48
Quality of life will be assessed with the Inflammatory Bowel Disease questionnaire scores
week 24 and week 48
UST trough levels and antidrug
Time Frame: week 12 and week 24
Correlation between response and remission and UST trough levels and antidrug (UST) antibodies
week 12 and week 24
Clinical response of UST optimization
Time Frame: week 24 and week 48
Number of participants with closure of at least 50% of all treated external openings that were draining at week 12
week 24 and week 48
Clinical response of UST introduction at week 12
Time Frame: week 24 and week 48
Number of participants with closure of at least 50% of all treated external openings that were draining at week 12
week 24 and week 48
CDAI
Time Frame: week 12, week 24 and week 48
Crohn Disease Activity Index
week 12, week 24 and week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

Collaborators

Janssen, LP

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 16, 2020

Primary Completion (Estimated)

June 30, 2024

Study Completion (Estimated)

June 30, 2025

Study Registration Dates

First Submitted

June 29, 2020

First Submitted That Met QC Criteria

July 30, 2020

First Posted (Actual)

August 3, 2020

Study Record Updates

Last Update Posted (Estimated)

January 19, 2024

Last Update Submitted That Met QC Criteria

January 18, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GT-2019-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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