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

September 2, 2020 updated by: IRCCS Burlo Garofolo

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
9

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Campania
      • Napoli, Campania, Italy, 80131
        • Dipartimento di Pediatria dell'Università di Napoli "Federico II"
    • Friuli Venezia Giulia
      • Trieste, Friuli Venezia Giulia, Italy, 34137
        • IRCCS Burlo Garofolo
    • Liguria
      • Genoa, Liguria, Italy, 16147
        • Pediatria III Gastroenterologia ed Endoscopia Digestiva, Istituto Giannina Gaslini
    • Lombardia
      • Monza, Lombardia, Italy, 20052
        • Fondazione MBBM , Azienda Ospedaliera San Gerardo - Università Milano Bicocca
    • Sicilia
      • Messina, Sicilia, Italy, 98124
        • Unità di Gastroenterologia Pediatrica e Fibrosi Cistica, Dipartimento di Scienze Pediatriche Mediche e Chirurgiche, Policlinico Universitario
    • Toscana
      • Firenze, Toscana, Italy, 50139
        • Gastroenterologia e Nutrizione Pediatrica, Azienda Ospedaliero Universitaria Meyer

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

6 years to 17 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
52 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
12 weeks
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.
52 weeks
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.
12 weeks
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.
52 weeks
Efficacy in reducing the need to change therapy
Time Frame: 12 weeks
Evaluation of the proportion of patients that need a therapeutic change
12 weeks
Efficacy in reducing the need to change therapy
Time Frame: 52 weeks
Evaluation of the proportion of patients that need a therapeutic change
52 weeks
Efficacy in reducing hospitalizations
Time Frame: 52 weeks
Evaluation of the proportion of patients that need hospitalization.
52 weeks
Efficacy in reducing the need for surgery
Time Frame: 52 weeks
Evaluation of the proportion of patients that need surgery
52 weeks
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)
Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks)
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)
Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks)
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
Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks)
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
Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks)
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
Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks)
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
Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks)
Evaluation of the Treatment-Emergent Adverse Events
Time Frame: Between enrolment and 52 weeks
Number and type
Between enrolment and 52 weeks
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
52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
IRCCS Burlo Garofolo

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Centro di Riferimento Oncologico - Aviano

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Alessandro Ventura, MD PhD, IRCCS Burlo Garofolo

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 27, 2018

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 31, 2020

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 31, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 5, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 14, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 18, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 4, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NET-2013-02355002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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