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

NCT03221166 | Terminated Phase 3

• 1 other identifier: NET-2013-02355002
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 6

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.

Conditions

Crohn Disease

Keywords

Children; Crohn disease; Thalidomide; Mucosal healing

Outcome Measures

Primary Outcomes (1)

• Efficacy in inducing mucosal healing

  Proportion of patients that achieve mucosal healing, defined by a Simplified Endoscopic Activity Index for CD (SES-CD) ≤ 2.

  52 weeks

Secondary Outcomes (16)

• Efficacy in inducing clinical response

  12 weeks

• Efficacy in inducing clinical response

  52 weeks

• Efficacy in inducing clinical remission

  12 weeks

• Efficacy in inducing clinical remission

  52 weeks

• Efficacy in reducing the need to change therapy

  12 weeks

Study Arms (2)

Thalidomide

EXPERIMENTAL

Thalidomide is a immunomodulatory and antiangiogenetic drug with anti tumor necrosis factor (TNF) alpha properties

Drug: Thalidomide

Infliximab

ACTIVE COMPARATOR

Infliximab is a chimeric monoclonal antibody against TNF alpha

Drug: Infliximab

Interventions

Thalidomide DRUG

Thalidomide is a immunomodulatory and antiangiogenetic drug with anti TNF alpha properties

Thalidomide

Infliximab DRUG

Infliximab is a chimeric monoclonal antibody against TNF alpha

Infliximab

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• IRCCS Burlo Garofolo: lead
• Centro di Riferimento Oncologico - Aviano: collaborator
• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia: collaborator

Study Sites (6)

Dipartimento di Pediatria dell'Università di Napoli "Federico II"

Napoli, Campania, 80131, Italy

Location

IRCCS Burlo Garofolo

Trieste, Friuli Venezia Giulia, 34137, Italy

Location

Pediatria III Gastroenterologia ed Endoscopia Digestiva, Istituto Giannina Gaslini

Genoa, Liguria, 16147, Italy

Location

Fondazione MBBM , Azienda Ospedaliera San Gerardo - Università Milano Bicocca

Monza, Lombardy, 20052, Italy

Location

Unità di Gastroenterologia Pediatrica e Fibrosi Cistica, Dipartimento di Scienze Pediatriche Mediche e Chirurgiche, Policlinico Universitario

Messina, Sicily, 98124, Italy

Location

Gastroenterologia e Nutrizione Pediatrica, Azienda Ospedaliero Universitaria Meyer

Florence, Tuscany, 50139, Italy

Location

MeSH Terms

Conditions

Crohn Disease

Interventions

Thalidomide; Infliximab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Alessandro Ventura, MD PhD

  IRCCS Burlo Garofolo

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2017
• First Posted: July 18, 2017
• Study Start: February 27, 2018
• Primary Completion: July 31, 2020
• Study Completion: July 31, 2020
• Last Updated: September 4, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (6)