Switching From Adalimumab to Infliximab (ADA-IFX)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by University Hospital, Ghent
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
University Hospital, Ghent
ClinicalTrials.gov Identifier:
NCT01338740
First received: April 18, 2011
Last updated: February 1, 2013
Last verified: February 2013
  Purpose

Switching to Adalimumab has proven to be efficacious in Crohn's disease (CD) patients with intolerance or loss of response to Infliximab. Currently there are no studies on the efficacy of switching to Infliximab in patients with loss of response or primary non-response to Adalimumab. Even in rheumatology, where switching between all classes of anti-TNFα biologicals is common practice, there are no scientific data on switching from humanized to chimeric anti-TNFα antibodies.

The purpose of this study is to document the efficacy of such a switch and to identify the possible predictive factors for success.

If treatment with Adalimumab fails (despite optimal dose and interval) and the treating physician therefore decided to switch to infliximab, the patient may be enrolled in this observational study. At regular intervals (every Remicade), the patient will be clinically re-evaluated. The disease activity score will be calculated: Crohn's disease activity index (CDAI). At regular intervals, the results of interim blood tests will be documented (3x). The succession will be 1 year. At week 10, 26 and 52, additional serum samples will be taken for determination of antibodies against Adalimumab and Infliximab. The serum levels of Adalimumab (week 0) and Infliximab (week 10, 26 and 52) will be determined.

For this study there is no specific therapy change. The study wants only to document the results of a therapy switch that, in current clinical practice, is made by the treating physician.


Condition Intervention
Crohn's Disease
Drug: Adalimumab and Infliximab

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Prospective Study to Assess the Efficacy of Switching to Infliximab in Moderately to Severely Active Chrohn's Disease Patients With Primary Non-response or Loss of Response to Adalimumab

Resource links provided by NLM:


Further study details as provided by University Hospital, Ghent:

Primary Outcome Measures:
  • Assess efficacy of switching from Adalimumab to Infliximab. [ Time Frame: after 10 weeks ] [ Designated as safety issue: No ]

    The primary objective of the study is to assess the efficacy of switching to Infliximab for the induction of clinical remission in subjects with moderately to severely active Crohn's disease with primary non-response or loss of response to Adalimumab.

    The proportion of subjects achieving clinical remission at week 10 after 3 infusions of Infliximab (week 0, 2 and 6). Clinical remission is defined as a total Crohn's Disease Activity Index (CDAI) score of 150 or less.



Secondary Outcome Measures:
  • induction of clinical response [ Time Frame: after 10 weeks ] [ Designated as safety issue: No ]
    To assess the efficacy of switching from Adalimumab to Infliximab for the induction of clinical response. The proportion of subjects with clinical response (at least 70 point decrease in Crohn's Disease Activity Index (CDAI)) at week 10.

  • induction of strong clinical response [ Time Frame: after 10 weeks ] [ Designated as safety issue: No ]

    To assess the efficacy of switching from Adalimumab to Infliximab for the induction of strong clinical response.

    The proportion of subjects with strong clinical response (at least 100 point decrease in CDAI) at week 10.


  • Sustained Clinical Response [ Time Frame: after 26 and 52 weeks ] [ Designated as safety issue: No ]

    To assess the efficacy of switching from Adalimumab to Infliximab to achieve sustained clinical response, treating with maintenance Infliximab infusions.

    The proportion of subjects with sustained clinical response (at least 100 and 70 point decrease in CDAI) at weeks 26 and 52.


  • Sustained Clinical Remission [ Time Frame: after 26 and 52 weeks ] [ Designated as safety issue: No ]

    To assess the efficacy of switching from Adalimumab to Infliximab to achieve sustained clinical remission, treating with maintenance Infliximab infusions.

    The proportion of subjects with sustained clinical remission (CDAI 150 or less) at weeks 26 and 52.


  • Induction and maintenance of steroid-free remission. [ Time Frame: after 10, 26 and 52 weeks ] [ Designated as safety issue: No ]

    To assess the efficacy of switching from Adalimumab to Infliximab for the induction and maintenance of steroid-free remission.

    The proportion of subjects with steroid-free remission (CDAI 150 or less) at weeks 10, 26 and 52.


  • Sustained clinical remission without need for Infliximab therapy optimization. [ Time Frame: after 26 and 52 weeks ] [ Designated as safety issue: No ]

    To assess the efficacy of switching from Adalimumab to Infliximab to achieve sustained clinical remission, treating with maintenance Infliximab infusions, without the need for Infliximab therapy optimization (interval shortening or dose increase).

    The proportion of subjects with sustained clinical remission (CDAI 150 or less) at weeks 26 and 52, without the need for Infliximab therapy optimization (interval shortening or dose increase).


  • Treatment failure [ Time Frame: during 52 weeks ] [ Designated as safety issue: No ]
    To assess the treatment failure of switching from Adalimumab to Infliximab. The proportion of patients with treatment failure. Failure is defined as cessation of Infliximab due to intolerance or insufficient efficacy despite therapy optimization or the start or dose increase of any other Crohn's disease medication during the study (including corticosteroids, immunosuppressants and 5-aminosalicylic acid (5-ASA) analogues).

  • Tolerance and safety for switching from Adalimumab to Infliximab. [ Time Frame: After 10, 26 and 52 weeks. ] [ Designated as safety issue: Yes ]
    Adverse events/Serious adverse events will be analysed. Hematology and biochemistry will be analysed at weeks 10, 26 and 52.

  • Serological factors associated with switching from Adalimumab to Infliximab. [ Time Frame: after 10, 26 and 52 weeks ] [ Designated as safety issue: No ]
    • C-Reactive Protein (CRP) at screening, weeks 10, 26 and 52.
    • Antibodies to Adalimumab at baseline, weeks 10, 26 and 52.
    • Trough level of Adalimumab at baseline.
    • Antibodies to Infliximab at weeks 10, 26 and 52.
    • Trough level of Infliximab at weeks 10, 26 and 52.


Biospecimen Retention:   Samples Without DNA

At regular intervals, the results of interim blood tests will be documented (3x).

After 10, 26 and 52 weeks, additional serum samples will be taken for determination of antibodies against Adalimumab and Infliximab. The serum levels of Adalimumab (week 0) and Infliximab (week 10, 26 and 52) will be determined.


Estimated Enrollment: 40
Study Start Date: April 2011
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Switch from Adalimumab to Infliximab
Moderately to severely active Crohn's disease patients with primary non-response or loss of response to Adalimumab, will switch to Infliximab.
Drug: Adalimumab and Infliximab
Patients with moderately to severely active Crohn's disease with primary non-response or loss of response to Adalimumab switch to Infliximab.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Patients with moderately to severely active Crohn's disease with primary non-response or loss of response to Adalimumab, switch to Infliximab.

Criteria

Inclusion Criteria:

  • Diagnosis of Crohn's disease confirmed by radiological, endoscopical or histological evidence.
  • Moderately to severely active Crohn's disease: Crohn's Disease Activity Index (CDAI) ≥ 220 ≤ 450, scored during the screening period.
  • Primary non-response to Adalimumab induction (160mg at week 0, 80 mg at week 2, then 40 mg every 2 weeks: q2w), defined as CDAI ≥ 220 in combination with C-Reactive Protein (CRP) ≥ 0.5mg/dl or endoscopic or radiological evidence of disease activity and evaluated 2 weeks after 6 injections (q2w) of Adalimumab (injections week 0 to week 10, evaluation week 12). OR Loss of response to Adalimumab, defined as CDAI ≥ 220 in combination with CRP ≥ 0.5mg/dl or endoscopic or radiological evidence of disease activity and after at least 4 weeks of weekly injections of Adalimumab (40mg).
  • Male or female aged 18-75 years old.
  • No history, signs or symptoms of active or latent, untreated tuberculosis (TB).
  • Having laboratory results as follows:

Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) levels not exceeding 2 times the upper limit of normal for the central laboratory conducting the test Serum creatinine not exceeding 1.7 mg/dl. Platelets ≥ 100 x 103 cells/µl. Neutrophils ≥ 1.5 x 103 cells/µl.

  • Having met all concomitant medication criteria:

Capable of providing informed consent, prior to any study related procedure.

Exclusion Criteria:

  • Exclusively fistulising Crohn's disease or exclusive involvement of the upper gastrointestinal (GI) tract.
  • Subject with abscess or suspicion of abscess.
  • Subject with obstructive fibrotic strictures (with prestenotic dilatation).
  • Subject with short bowel syndrome.
  • Subject who has had a surgical bowel resection within the past 6 months or planning of any resection at the time while enrolled in the study.
  • Subject with Ulcerative Colitis or Indeterminant Colitis.
  • Subject with ostomy or ileoanal pouch.
  • Subject who is currently receiving total parenteral nutrition.
  • Subject who has previously been treated with Infliximab or Certolizumab Pegol.
  • Subject with positive stool cultures for enteric pathogens or positive C. difficile toxins during screening period.
  • Subject who has received any investigational drug within 12 weeks prior to screening.
  • Subject with a history of drug or alcohol abuse within the past 3 years.
  • Females who are pregnant or breast feeding.
  • Females of child bearing age not practicing effective birth control.
  • Subject with a history of malignancy irrespective of time (except carcinoma- in situ of cervix or basal cell carcinoma or squamous cell carcinoma that was successfully treated).
  • Subject with a history or symptoms of lymphoproliferative disease.
  • Subject with a history of Human Immunodeficiency Virus (HIV), chronic or active Hepatitis B.
  • History of Congestive Heart Failure (CHF), including medically controlled asymptomatic CHF.
  • Subject who currently has or had an opportunistic infection (e.g. cytomegalovirus (CMV), pneumocystis carinii, aspergillosis, histoplasmosis, coccidioidomycosis) within 6 months prior to screening.
  • Subject who currently has an active infection.
  • Subject who has a transplanted organ (except for corneal transplant).
  • History of known demyelinating disease such as optic neuritis or multiple sclerosis.
  • Signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, psychiatric or cerebral disease.

CONCOMITANT MEDICATION

  1. Corticosteroids (prednisone, (methyl)prednisolone, budesonide):

    stable dose for 2 weeks prior to baseline, then tapering at the discretion of the investigator.

  2. Immunosuppressants (azathioprine, 6-mercaptopurine, methotrexate):

    patients taking this medication prior to baseline: stable dose for 8 weeks prior to baseline, then stable dose until week 26 of the study. Starting or restarting of immunosuppressants is allowed until week 2, then stable dose until week 26 of the study.

  3. 5-ASA analogues (sulphasalazine, mesalazine): stable dose for 4 weeks prior to baseline, stable dose until week 26 of the study.
  4. Antibiotics (e.g. quinolone, metronidazole): stable dose for 2 weeks prior to baseline.
  5. Adalimumab: at least 2 week washout period prior to first Infliximab infusion.

Starting or increasing the dose of other medication for Crohn's disease than Infliximab during the study will be considered as "treatment failure". (except for immunosuppressants as described above under 2.)

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01338740

Contacts
Contact: Harald Peeters, Ph.D., M.D. Harald.Peeters@ugent.be

Locations
Belgium
Sint-Augustinus Not yet recruiting
Antwerp, Belgium
Contact: Frank Van De Mierop, M.D.       frank.vandemierop@gza.be   
Principal Investigator: Frank Van De Mierop, M.D.         
UZ Antwerpen Recruiting
Antwerp, Belgium
Contact: Tom Moreels, M.D.       tom.moreels@uza.be   
Principal Investigator: Tom Moreels, M.D.         
Imelda Hospital Not yet recruiting
Bonheiden, Belgium
Contact: Peter Bossuyt, M.D.       Peter.Bossuyt@imelda.be   
Principal Investigator: Peter Bossuyt, M.D.         
ULB université libre (erasme) Not yet recruiting
Brussels, Belgium
Contact: Denis Franchimont, M.D.       denis.franchimont@ulb.ac.be   
Principal Investigator: Denis Franchimont, M.D.         
Cliniques Universitaires Saint-Luc Not yet recruiting
Brussels, Belgium
Contact: Olivier Dewit, M.D.       Olivier.Dewit@clin.ucl.ac.be   
Principal Investigator: Olivier Dewit, M.D.         
Ziekenhuis Oost-Limburg Not yet recruiting
Genk, Belgium
Contact: Philip Caenepeel, M.D.       philip.caenepeel@zol.be   
Principal Investigator: Philip Caenepeel, M.D.         
Sub-Investigator: Evelien Humblet, M.D.         
University Hospital Ghent Recruiting
Ghent, Belgium
Contact: Harald Peeters, Ph.D. , M.D.         
Principal Investigator: Harald Peeters, Ph.D., M.D.         
Sub-Investigator: Martine De Vos, Ph.D., M.D.         
Virga Jesse hospital Recruiting
Hasselt, Belgium
Contact: Jean-Louis Coenegrachts, M.D.       jean-louis.coenegrachts@virgajesse.be   
Principal Investigator: Jean-Louis Coenegrachts, M.D.         
AZ Groeninge Recruiting
Kortrijk, Belgium
Contact: François D'Heygere, M.D.       francois.dheygere@azgroeninge.be   
Principal Investigator: François D'Heygere, M.D.         
UZ Leuven Recruiting
Leuven, Belgium
Contact: Séverine Vermeire, M.D.       Severine.Vermeire@uz.kuleuven.ac.be   
Principal Investigator: Séverine Vermeire, M.D.         
CHC (Centre Hospitalier Chrétien) Not yet recruiting
Liège, Belgium
Contact: Arnaud Colard       arnaud.colard@chc.be   
Principal Investigator: Arnaud Colard, M.D.         
Sub-Investigator: Fernand Fontaine, M.D.         
CHU de liège Not yet recruiting
Liège, Belgium
Contact: Edouard Louis, M.D.       Edouard.Louis@ulg.ac.be   
Principal Investigator: Edouard Louis, M.D.         
Hospital Maas en kempen Not yet recruiting
Maaseik, Belgium
Contact: Stefan Delen, M.D.       stefandelen@hotmail.com   
Principal Investigator: Stefan Delen, M.D.         
AZ Damiaan Recruiting
Oostende, Belgium
Contact: Guy Lambrecht, M.D.       glambrecht@azdamiaan.be   
Principal Investigator: Guy Lambrecht, M.D.         
Clinique Saint-Pierre Recruiting
Ottignies, Belgium
Contact: Jean-Charles Coche, M.D.       jc.coche@clinique-saint-pierre.be   
Principal Investigator: Jean-Charles Coche, M.D.         
Heilig Hartziekenhuis Roeselare Recruiting
Roeselare, Belgium
Contact: Filip Baert, M.D.       fbaert@hhr.be   
Principal Investigator: Filip Baert, M.D.         
Sponsors and Collaborators
University Hospital, Ghent
Abbott
Investigators
Principal Investigator: Harald Peeters, Ph.D. , M.D. University Hospital, Ghent
  More Information

Additional Information:
No publications provided

Responsible Party: University Hospital, Ghent
ClinicalTrials.gov Identifier: NCT01338740     History of Changes
Other Study ID Numbers: 2010/566
Study First Received: April 18, 2011
Last Updated: February 1, 2013
Health Authority: Belgium: Ethics Committee

Keywords provided by University Hospital, Ghent:
Chrohn's disease
Moderate to severely active Crohn's disease patients

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Infliximab
Adalimumab
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Dermatologic Agents
Gastrointestinal Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on October 19, 2014