Switching From Adalimumab to Infliximab

NCT01338740 | Completed

• 1 other identifier: 2010/566
• Study Type: observational
• Target: 21
• Locations: 1 country
• Sites: 16

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

Keywords

Chrohn's disease; Moderate to severely active Crohn's disease patients

Outcome Measures

Primary Outcomes (1)

• Assess efficacy of switching from Adalimumab to Infliximab.

  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.

  after 10 weeks

Secondary Outcomes (9)

• induction of clinical response

  after 10 weeks

• induction of strong clinical response

  after 10 weeks

• Sustained Clinical Response

  after 26 and 52 weeks

• Sustained Clinical Remission

  after 26 and 52 weeks

• Induction and maintenance of steroid-free remission.

  after 10, 26 and 52 weeks

Study Arms (1)

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

Interventions

Adalimumab and Infliximab DRUG

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

Switch from Adalimumab to Infliximab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University Hospital, Ghent: lead
• Abbott: collaborator

Study Sites (16)

Sint-Augustinus

Antwerp, Belgium

Location

UZ Antwerpen

Antwerp, Belgium

Location

Imelda Hospital

Bonheiden, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

ULB université libre (erasme)

Brussels, Belgium

Location

Ziekenhuis Oost-Limburg

Genk, Belgium

Location

University Hospital Ghent

Ghent, Belgium

Location

Virga Jesse hospital

Hasselt, Belgium

Location

AZ Groeninge

Kortrijk, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

CHC (Centre Hospitalier Chrétien)

Liège, Belgium

Location

CHU de liège

Liège, Belgium

Location

Hospital Maas en kempen

Maaseik, Belgium

Location

AZ Damiaan

Ostend, Belgium

Location

Clinique Saint-Pierre

Ottignies, Belgium

Location

Heilig Hartziekenhuis Roeselare

Roeselare, Belgium

Location

Related Links

• Related Info

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.

MeSH Terms

Conditions

Crohn Disease

Interventions

Adalimumab; Infliximab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Harald Peeters, Ph.D., M.D.

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2011
• First Posted: April 19, 2011
• Study Start: April 1, 2011
• Primary Completion: February 17, 2014
• Study Completion: February 17, 2014
• Last Updated: January 5, 2023

Record last verified: 2023-01

Locations

BE (16)