AzTrials
AzTrials

Crohn DiseasePhase 3NCT03221166

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

A Phase 3 study testing Thalidomide and Infliximab in people with Crohn Disease, run by IRCCS Burlo Garofolo at 6 sites in Italy.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 6 to 17 years
Conditions the study is for
Crohn Disease
What is being tested?
Thalidomide and Infliximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
6 sitesItaly
Study dates
27 Feb 2018to 31 Jul 2020
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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
Show all 11Show fewer
  • 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.

Who cannot join

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

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Italy6 sites

  • Gastroenterologia e Nutrizione Pediatrica, Azienda Ospedaliero Universitaria Meyer

    Florence, Tuscany, 50139

  • Pediatria III Gastroenterologia ed Endoscopia Digestiva, Istituto Giannina Gaslini

    Genoa, Liguria, 16147

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

    Messina, Sicily, 98124

  • Fondazione MBBM , Azienda Ospedaliera San Gerardo - Università Milano Bicocca

    Monza, Lombardy, 20052

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

    Naples, Campania, 80131

  • IRCCS Burlo Garofolo

    Trieste, Friuli Venezia Giulia, 34137

Other trials in Italy

About this study

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

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
Being tested
Thalidomide, Infliximab
Keywords
Children, Crohn disease, Thalidomide, Mucosal healing
Medical subject headings
Crohn Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ThalidomideDrug

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

  • InfliximabDrug

    Infliximab is a chimeric monoclonal antibody against TNF alpha

Study groups in NCT03221166
Study groupRoleWhat they receive
ThalidomideExperimentalThalidomide is a immunomodulatory and antiangiogenetic drug with anti tumor necrosis factor (TNF) alpha properties
Receives: Drug: Thalidomide
InfliximabActive comparatorInfliximab is a chimeric monoclonal antibody against TNF alpha
Receives: Drug: Infliximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 52 weeks

Secondary outcomes (16)

  1. Efficacy in inducing clinical response

    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.

    Measured: 12 weeks

  2. Efficacy in inducing clinical response

    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.

    Measured: 52 weeks

  3. Efficacy in inducing clinical remission

    Clinical remission will be evaluated with the weighted Pediatric Crohn's Disease Activity Index (wPCDAI), defined by a wPCDAI <12.5.

    Measured: 12 weeks

  4. Efficacy in inducing clinical remission

    Clinical remission will be evaluated with the weighted Pediatric Crohn's Disease Activity Index (wPCDAI), defined by a wPCDAI <12.5.

    Measured: 52 weeks

  5. Efficacy in reducing the need to change therapy

    Evaluation of the proportion of patients that need a therapeutic change

    Measured: 12 weeks

  6. Efficacy in reducing the need to change therapy

    Evaluation of the proportion of patients that need a therapeutic change

    Measured: 52 weeks

  7. Efficacy in reducing hospitalizations

    Evaluation of the proportion of patients that need hospitalization.

    Measured: 52 weeks

  8. Efficacy in reducing the need for surgery

    Evaluation of the proportion of patients that need surgery

    Measured: 52 weeks

  9. Efficacy in reducing erythrocyte sedimentation rate

    Evaluation of the trend of erythrocyte sedimentation rate (ESR)

    Measured: Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks)

  10. Efficacy in reducing C-reactive protein

    Evaluation of the trend of C-reactive protein (CRP)

    Measured: Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks)

  11. Efficacy in reducing faecal calprotectin

    Evaluation of the trend of faecal calprotectin

    Measured: Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks)

  12. Efficacy in modifying body mass index

    Evaluation of the trend of body mass index, defined as weight (kg)/height (m)^2

    Measured: Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks)

  13. Efficacy in modifying height-for-age z score

    Evaluation of the trend of height-for-age z score

    Measured: Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks)

  14. Efficacy in modifying weight-for-age z score

    Evaluation of the trend of weight-for-age z score

    Measured: Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks)

  15. Evaluation of the Treatment-Emergent Adverse Events

    Number and type

    Measured: Between enrolment and 52 weeks

  16. Direct and indirect costs

    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

    Measured: 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jul 2017
  2. Study start27 Feb 2018
  3. Primary completion31 Jul 2020
  4. Study completion31 Jul 2020

Why it stopped: Difficulty in recruiting subjects who meet the inclusion/exclusion criteria

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03221166
Sponsor's protocol ID
NET-2013-02355002
Status last verified
Sep 2020
First submitted
5 Jul 2017
Last updated
4 Sep 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Thalidomide and Infliximab in people with Crohn Disease, run by IRCCS Burlo Garofolo at 6 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Difficulty in recruiting subjects who meet the inclusion/exclusion criteria). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy in inducing mucosal healing (time frame: 52 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03221166.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in