Clinical trial NCT01338740: Switching From Adalimumab to Infliximab
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Crohn's Disease
Keywords: Chrohn's disease
Moderate to severely active Crohn's disease patients
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2011-04-19
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

Brief summary: 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.


Eligibility 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.)

Primary outcomes:
measure: Assess efficacy of switching from Adalimumab to Infliximab.
timeFrame: after 10 weeks
Secondary outcomes:
measure: induction of clinical response
timeFrame: after 10 weeks
measure: induction of strong clinical response
timeFrame: after 10 weeks
measure: Sustained Clinical Response
timeFrame: after 26 and 52 weeks
measure: Sustained Clinical Remission
timeFrame: after 26 and 52 weeks
measure: Induction and maintenance of steroid-free remission.
timeFrame: after 10, 26 and 52 weeks
measure: Sustained clinical remission without need for Infliximab therapy optimization.
timeFrame: after 26 and 52 weeks
measure: Treatment failure
timeFrame: during 52 weeks
measure: Tolerance and safety for switching from Adalimumab to Infliximab.
timeFrame: After 10, 26 and 52 weeks.
measure: Serological factors associated with switching from Adalimumab to Infliximab.
timeFrame: after 10, 26 and 52 weeks
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Sint-Augustinus
city: Antwerp
country: Belgium
facility: UZ Antwerpen
city: Bonheiden
country: Belgium
facility: Imelda Hospital
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Brussels
country: Belgium
facility: ULB université libre (erasme)
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg
city: Ghent
country: Belgium
facility: University Hospital Ghent
city: Hasselt
country: Belgium
facility: Virga Jesse hospital
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: CHC (Centre Hospitalier Chrétien)
city: Liège
country: Belgium
facility: CHU de liège
city: Maaseik
country: Belgium
facility: Hospital Maas en kempen
city: Oostende
country: Belgium
facility: AZ Damiaan
city: Ottignies
country: Belgium
facility: Clinique Saint-Pierre
city: Roeselare
country: Belgium
facility: Heilig Hartziekenhuis Roeselare
Study officials:
affiliation: University Hospital, Ghent
name: Harald Peeters, Ph.D., M.D.
role: PRINCIPAL_INVESTIGATOR
References: