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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 : Terminated (Difficulty in recruiting subjects who meet the inclusion/exclusion criteria)
First Posted : July 18, 2017
Last Update Posted : September 4, 2020
Sponsor:
Collaborators:
Centro di Riferimento Oncologico - Aviano
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Information provided by (Responsible Party):
IRCCS Burlo Garofolo

Tracking Information
First Submitted Date  ICMJE July 5, 2017
First Posted Date  ICMJE July 18, 2017
Last Update Posted Date September 4, 2020
Actual Study Start Date  ICMJE February 27, 2018
Actual Primary Completion Date July 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 14, 2017)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2017)
  • 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.
  • 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.
  • 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.
  • 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.
  • Efficacy in reducing the need to change therapy [ Time Frame: 12 weeks ]
    Evaluation of the proportion of patients that need a therapeutic change
  • Efficacy in reducing the need to change therapy [ Time Frame: 52 weeks ]
    Evaluation of the proportion of patients that need a therapeutic change
  • Efficacy in reducing hospitalizations [ Time Frame: 52 weeks ]
    Evaluation of the proportion of patients that need hospitalization.
  • Efficacy in reducing the need for surgery [ Time Frame: 52 weeks ]
    Evaluation of the proportion of patients that need surgery
  • 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)
  • 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)
  • 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
  • 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
  • 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
  • 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
  • Evaluation of the Treatment-Emergent Adverse Events [ Time Frame: Between enrolment and 52 weeks ]
    Number and type
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: July 14, 2017)
  • 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.
  • 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.
  • 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.
  • 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.
  • Efficacy in reducing the need to change therapy [ Time Frame: 12 weeks ]
    Evaluation of the proportion of patients that need a therapeutic change
  • Efficacy in reducing the need to change therapy [ Time Frame: 52 weeks ]
    Evaluation of the proportion of patients that need a therapeutic change
  • Efficacy in reducing hospitalizations [ Time Frame: 52 weeks ]
    Evaluation of the proportion of patients that need hospitalization.
  • Efficacy in reducing the need for surgery [ Time Frame: 52 weeks ]
    Evaluation of the proportion of patients that need surgery
  • 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)
  • 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)
  • 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
  • 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
  • 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
  • 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
  • Evaluation of the Treatment-Emergent Adverse Events [ Time Frame: Between enrolment and 52 weeks ]
    Number and type
  • Direct and indirect costs [ Time Frame: 52 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Thalidomide Versus Infliximab in New Onset Crohn's Disease With Poor Prognostic Factors
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Crohn Disease
Intervention  ICMJE
  • Drug: Thalidomide
    Thalidomide is a immunomodulatory and antiangiogenetic drug with anti TNF alpha properties
  • Drug: Infliximab
    Infliximab is a chimeric monoclonal antibody against TNF alpha
Study Arms  ICMJE
  • Experimental: Thalidomide
    Thalidomide is a immunomodulatory and antiangiogenetic drug with anti tumor necrosis factor (TNF) alpha properties
    Intervention: Drug: Thalidomide
  • Active Comparator: Infliximab
    Infliximab is a chimeric monoclonal antibody against TNF alpha
    Intervention: Drug: Infliximab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 2, 2020)
9
Original Estimated Enrollment  ICMJE
 (submitted: July 14, 2017)
124
Actual Study Completion Date  ICMJE July 31, 2020
Actual Primary Completion Date July 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03221166
Other Study ID Numbers  ICMJE NET-2013-02355002
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party IRCCS Burlo Garofolo
Study Sponsor  ICMJE IRCCS Burlo Garofolo
Collaborators  ICMJE
  • Centro di Riferimento Oncologico - Aviano
  • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Investigators  ICMJE
Study Chair: Alessandro Ventura, MD PhD IRCCS Burlo Garofolo
PRS Account IRCCS Burlo Garofolo
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP