Clinical trial NCT03221166: Thalidomide Versus Infliximab in New Onset Crohn's Disease With Poor Prognostic Factors
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Crohn Disease
Keywords: Children
Crohn disease
Thalidomide
Mucosal healing
Lead sponsor: IRCCS Burlo Garofolo
Sponsor class: OTHER
Collaborators: name: Centro di Riferimento Oncologico - Aviano
name: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
First posted: 2017-07-18
Enrollment: 9
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Efficacy in inducing mucosal healing
timeFrame: 52 weeks
Secondary outcomes:
measure: Efficacy in inducing clinical response
timeFrame: 12 weeks
measure: Efficacy in inducing clinical response
timeFrame: 52 weeks
measure: Efficacy in inducing clinical remission
timeFrame: 12 weeks
measure: Efficacy in inducing clinical remission
timeFrame: 52 weeks
measure: Efficacy in reducing the need to change therapy
timeFrame: 12 weeks
measure: Efficacy in reducing the need to change therapy
timeFrame: 52 weeks
measure: Efficacy in reducing hospitalizations
timeFrame: 52 weeks
measure: Efficacy in reducing the need for surgery
timeFrame: 52 weeks
measure: Efficacy in reducing erythrocyte sedimentation rate
timeFrame: Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks)
measure: Efficacy in reducing C-reactive protein
timeFrame: Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks)
measure: Efficacy in reducing faecal calprotectin
timeFrame: Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks)
measure: Efficacy in modifying body mass index
timeFrame: Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks)
measure: Efficacy in modifying height-for-age z score
timeFrame: Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks)
measure: Efficacy in modifying weight-for-age z score
timeFrame: Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks)
measure: Evaluation of the Treatment-Emergent Adverse Events
timeFrame: Between enrolment and 52 weeks
measure: Direct and indirect costs
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Napoli
country: Italy
facility: Dipartimento di Pediatria dell'Università di Napoli "Federico II"
state: Campania
city: Trieste
country: Italy
facility: IRCCS Burlo Garofolo
state: Friuli Venezia Giulia
city: Genoa
country: Italy
facility: Pediatria III Gastroenterologia ed Endoscopia Digestiva, Istituto Giannina Gaslini
state: Liguria
city: Monza
country: Italy
facility: Fondazione MBBM , Azienda Ospedaliera San Gerardo - Università Milano Bicocca
state: Lombardia
city: Messina
country: Italy
facility: Unità di Gastroenterologia Pediatrica e Fibrosi Cistica, Dipartimento di Scienze Pediatriche Mediche e Chirurgiche, Policlinico Universitario
state: Sicilia
city: Firenze
country: Italy
facility: Gastroenterologia e Nutrizione Pediatrica, Azienda Ospedaliero Universitaria Meyer
state: Toscana
Study officials:
affiliation: IRCCS Burlo Garofolo
name: Alessandro Ventura, MD PhD
role: STUDY_CHAIR
References: