Switching From Adalimumab to Infliximab

NCT ID: NCT01338740

Last Updated: 2023-01-05

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 21 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2014-02-17

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.

Conditions

Crohn's Disease

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

Adalimumab and Infliximab

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

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.)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Abbott

INDUSTRY

Sponsor Role: collaborator

University Hospital, Ghent

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Harald Peeters, Ph.D., M.D.

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Ghent

Locations

Sint-Augustinus

Antwerp, , Belgium

UZ Antwerpen

Antwerp, , Belgium

Imelda Hospital

Bonheiden, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

ULB université libre (erasme)

Brussels, , Belgium

Ziekenhuis Oost-Limburg

Genk, , Belgium

University Hospital Ghent

Ghent, , Belgium

Virga Jesse hospital

Hasselt, , Belgium

AZ Groeninge

Kortrijk, , Belgium

UZ Leuven

Leuven, , Belgium

CHC (Centre Hospitalier Chrétien)

Liège, , Belgium

CHU de liège

Liège, , Belgium

Hospital Maas en kempen

Maaseik, , Belgium

AZ Damiaan

Ostend, , Belgium

Clinique Saint-Pierre

Ottignies, , Belgium

Heilig Hartziekenhuis Roeselare

Roeselare, , Belgium

Countries

Belgium

Related Links

http://www.uzgent.be

Related Info

Other Identifiers

2010/566

Identifier Type: -

Identifier Source: org_study_id