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

NCT ID: NCT03221166

Last Updated: 2020-09-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-27
• Study Completion Date: 2020-07-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Thalidomide

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

Group Type: EXPERIMENTAL

Thalidomide

Intervention Type: DRUG

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

Infliximab

Infliximab is a chimeric monoclonal antibody against TNF alpha

Group Type: ACTIVE_COMPARATOR

Infliximab

Intervention Type: DRUG

Infliximab is a chimeric monoclonal antibody against TNF alpha

Interventions

Thalidomide

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

Intervention Type: DRUG

Infliximab

Infliximab is a chimeric monoclonal antibody against TNF alpha

Intervention Type: DRUG

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centro di Riferimento Oncologico - Aviano

OTHER

Sponsor Role: collaborator

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

OTHER

Sponsor Role: collaborator

IRCCS Burlo Garofolo

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alessandro Ventura, MD PhD

Role: STUDY_CHAIR

IRCCS Burlo Garofolo

Locations

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

Napoli, Campania, Italy

IRCCS Burlo Garofolo

Trieste, Friuli Venezia Giulia, Italy

Pediatria III Gastroenterologia ed Endoscopia Digestiva, Istituto Giannina Gaslini

Genoa, Liguria, Italy

Fondazione MBBM , Azienda Ospedaliera San Gerardo - Università Milano Bicocca

Monza, Lombardy, Italy

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

Messina, Sicily, Italy

Gastroenterologia e Nutrizione Pediatrica, Azienda Ospedaliero Universitaria Meyer

Florence, Tuscany, Italy

Countries

Italy

Other Identifiers

NET-2013-02355002

Identifier Type: -

Identifier Source: org_study_id