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Thalidomide Versus Infliximab in New Onset Crohn's Disease With Poor Prognostic Factors

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ClinicalTrials.gov Identifier: NCT03221166
Recruitment Status : Recruiting
First Posted : July 18, 2017
Last Update Posted : April 9, 2018
Sponsor:
Collaborators:
Centro di Riferimento Oncologico - Aviano
Azienda Ospedaliera Spedali Civili di Brescia
Information provided by (Responsible Party):
IRCCS Burlo Garofolo

Brief Summary:

Crohn's disease (CD) is a life-long inflammatory bowel disease disease with an unknown pathogenesis. The ultimate goal of therapy is to modify the natural history of CD thus reducing complications. Thalidomide is a small molecule with immunomodulatory and anti-angiogenetic properties. It is currently approved for the treatment of erythema nodosum leprosum, an immunological complication of leprosy and multiple myeloma. It has also been used in several other inflammatory diseases of the skin and of the mucosal membranes, such as Behcet disease, oropharyngeal ulcers in AIDS, cutaneous lupus, and graft versus host disease. Many case series and one pediatric randomized controlled trial proved the efficacy of thalidomide in the treatment of children with CD refractory to standard treatments. In these patients, clinical remission was achieved in about 50% of the cases and was maintained for a mean time superior of 3 years. Mucosal healing after 52 weeks of treatment was observed in 40% of the patients in clinical remission. Moreover, thalidomide was found to have a steroid-sparing effect and to decrease the need for surgical interventions. The clinical and endoscopic efficacy of thalidomide was also observed in children with failure to respond or intolerance to anti-TNF biological drugs.

The aim of this multicentric prospective randomized controlled is to evaluate the efficacy and safety of thalidomide vs infliximab in changing the natural history of CD in patients with poor prognostic outcome. Moreover, the study will evaluate the immunological and genetical mechanisms of CD, the mechanisms of action thalidomide in CD and will the pharmacokinetics, metabolomics and pharmacogenomics of thalidomide, and their impact on thalidomide safety and effectiveness.


Condition or disease Intervention/treatment Phase
Crohn Disease Drug: Thalidomide Drug: Infliximab Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 124 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Thalidomide, a Novel Immunological Treatment to Modify the Natural History of Paediatric Crohn's Disease: a New Proposal From a Well-established Paediatric Research Network
Actual Study Start Date : February 27, 2018
Estimated Primary Completion Date : October 31, 2019
Estimated Study Completion Date : September 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arm Intervention/treatment
Experimental: Thalidomide
Thalidomide is a immunomodulatory and antiangiogenetic drug with anti tumor necrosis factor (TNF) alpha properties
Drug: Thalidomide
Thalidomide is a immunomodulatory and antiangiogenetic drug with anti TNF alpha properties

Active Comparator: Infliximab
Infliximab is a chimeric monoclonal antibody against TNF alpha
Drug: Infliximab
Infliximab is a chimeric monoclonal antibody against TNF alpha




Primary Outcome Measures :
  1. Efficacy in inducing mucosal healing [ Time Frame: 52 weeks ]
    Proportion of patients that achieve mucosal healing, defined by a Simplified Endoscopic Activity Index for CD (SES-CD) ≤ 2.


Secondary Outcome Measures :
  1. Efficacy in inducing clinical response [ Time Frame: 12 weeks ]
    Clinical response will be evaluated with the weighted Pediatric Crohn's Disease Activity Index (wPCDAI), defined by a reduction of wPCDAI > 50% from the basal values.

  2. Efficacy in inducing clinical response [ Time Frame: 52 weeks ]
    Clinical response will be evaluated with the weighted Pediatric Crohn's Disease Activity Index (wPCDAI), defined by a reduction of wPCDAI > 50% from the basal values.

  3. Efficacy in inducing clinical remission [ Time Frame: 12 weeks ]
    Clinical remission will be evaluated with the weighted Pediatric Crohn's Disease Activity Index (wPCDAI), defined by a wPCDAI <12.5.

  4. Efficacy in inducing clinical remission [ Time Frame: 52 weeks ]
    Clinical remission will be evaluated with the weighted Pediatric Crohn's Disease Activity Index (wPCDAI), defined by a wPCDAI <12.5.

  5. Efficacy in reducing the need to change therapy [ Time Frame: 12 weeks ]
    Evaluation of the proportion of patients that need a therapeutic change

  6. Efficacy in reducing the need to change therapy [ Time Frame: 52 weeks ]
    Evaluation of the proportion of patients that need a therapeutic change

  7. Efficacy in reducing hospitalizations [ Time Frame: 52 weeks ]
    Evaluation of the proportion of patients that need hospitalization.

  8. Efficacy in reducing the need for surgery [ Time Frame: 52 weeks ]
    Evaluation of the proportion of patients that need surgery

  9. Efficacy in reducing erythrocyte sedimentation rate [ Time Frame: Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks) ]
    Evaluation of the trend of erythrocyte sedimentation rate (ESR)

  10. Efficacy in reducing C-reactive protein [ Time Frame: Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks) ]
    Evaluation of the trend of C-reactive protein (CRP)

  11. Efficacy in reducing faecal calprotectin [ Time Frame: Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks) ]
    Evaluation of the trend of faecal calprotectin

  12. Efficacy in modifying body mass index [ Time Frame: Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks) ]
    Evaluation of the trend of body mass index, defined as weight (kg)/height (m)^2

  13. Efficacy in modifying height-for-age z score [ Time Frame: Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks) ]
    Evaluation of the trend of height-for-age z score

  14. Efficacy in modifying weight-for-age z score [ Time Frame: Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks) ]
    Evaluation of the trend of weight-for-age z score

  15. Evaluation of the Treatment-Emergent Adverse Events [ Time Frame: Between enrolment and 52 weeks ]
    Number and type

  16. Direct and indirect costs [ Time Frame: 52 weeks ]
    Comparison of direct and indirect costs (i.e. drugs, medical supplies and equipment, laboratory and diagnostic tests, hospitalizations, visits, transportation to and from healthcare facilities, missing work and school days…) between the two groups



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age at diagnosis <18 years and >=6 years
  • New diagnosis of CD based on Porto criteria
  • CD with inflammatory phenotype (non-penetrating, non-fistulizing) and with no need for surgery except for perinal fistulas
  • Presence of at least one of the following risk factors for poor prognosis:

    • fistulizing perianal disease
    • pan-enteric disease
    • disease extension > 60 cm
    • severe growth delay (height z-score < -2 DS)
    • severe osteoporosis (z score < -2 DS)
    • hypoalbuminemia (< 3g/dL) or high C-reactive protein (2 times higher the normal range)
  • Acceptance of the Risk Evaluation and Mitigation Strategy (REMS) program for reducing the teratogenic risk.

Exclusion Criteria:

  • ongoing pregnancy
  • presence of peripheral neuropathy
  • HIV
  • patients with transplanted organs
  • ongoing major infections or other severe diseases
  • participation to other experimental studies.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03221166


Contacts
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Contact: Matteo Bramuzzo, MD +39.040.3785.312 matteo.bramuzzo@burlo.trieste.it
Contact: Luca Ronfani, MD PhD +39.040.3785.401 luca.ronfani@burlo.trieste.it

Locations
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Italy
Dipartimento di Pediatria dell'Università di Napoli "Federico II" Not yet recruiting
Napoli, Campania, Italy, 80131
Contact: Erasmo Miele, MD, PhD    +39 081 7464565    erasmo.miele@unina.it   
IRCCS Burlo Garofolo Not yet recruiting
Trieste, Friuli Venezia Giulia, Italy, 34137
Contact: Matteo Bramuzzo, MD    +39 040 3785312    matteo.bramuzzo@burlo.trieste.it   
Pediatria III Gastroenterologia ed Endoscopia Digestiva, Istituto Giannina Gaslini Recruiting
Genoa, Liguria, Italy, 16147
Contact: Arrigo Barabino, MD    +39 010 5636350    arrigobarabino@gaslini.org   
Fondazione MBBM , Azienda Ospedaliera San Gerardo - Università Milano Bicocca Not yet recruiting
Monza, Lombardia, Italy, 20052
Contact: Roberto Panceri, MD    +390392333515    rpanceri@asst-monza.it   
Unità di Gastroenterologia Pediatrica e Fibrosi Cistica, Dipartimento di Scienze Pediatriche Mediche e Chirurgiche, Policlinico Universitario Not yet recruiting
Messina, Sicilia, Italy, 98124
Contact: Giuseppe Magazzu, MD    +39 090 2213160    giuseppe.magazzu@unime.it   
Gastroenterologia e Nutrizione Pediatrica, Azienda Ospedaliero Universitaria Meyer Not yet recruiting
Firenze, Toscana, Italy, 50139
Contact: Paolo Lionetti, MD, PhD    +39 055 5662950    paolo.lionetti@unifi.it   
Sponsors and Collaborators
IRCCS Burlo Garofolo
Centro di Riferimento Oncologico - Aviano
Azienda Ospedaliera Spedali Civili di Brescia
Investigators
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Study Chair: Alessandro Ventura, MD PhD IRCCS Burlo Garofolo

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Responsible Party: IRCCS Burlo Garofolo
ClinicalTrials.gov Identifier: NCT03221166     History of Changes
Other Study ID Numbers: NET-2013-02355002
First Posted: July 18, 2017    Key Record Dates
Last Update Posted: April 9, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by IRCCS Burlo Garofolo:
Children
Crohn disease
Thalidomide
Mucosal healing

Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Infliximab
Thalidomide
Dermatologic Agents
Gastrointestinal Agents
Antirheumatic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents