Crohn's DiseasePhase 4NCT00851565
Use of Combined Measurements of Serum Infliximab and Anti-infliximab Antibodies in the Treatment of Patients With Crohns Disease Failing Infliximab Therapy
A Phase 4 study testing Measurement of serum infliximab and anti-infliximab antibodies and Treatment according to current standards without knowledge of serum infliximab and anti-infliximab Ab status in people with Crohn's Disease, run by Copenhagen University Hospital at Herlev at 8 sites in Denmark.
Trial summary
To compare treatment outcome in patients with Crohn's disease with secondary loss of response to infliximab (i.e. initial good response follow by loss of response) treated according to current standards based only on clinical features versus treatment based on serum levels of infliximab and anti-infliximab antibody… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Crohn's Disease
- What is being tested?
- Measurement of serum infliximab and anti-infliximab antibodies and Treatment according to current standards without knowledge of serum infliximab and anti-infliximab Ab status
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 8 sitesDenmark
- Study dates
- Jun 2009to Feb 2014
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must be able to understand the information given to him/her and give written informed consent.
- Definitive diagnosis of Crohn's disease (confirmed by recent radiological, endoscopic and/or histological evidence according to international criteria) .
- Age minimum 18 years.
- Previous good response to at least 3 doses (5mg/kg) of infliximab (as judged by the treating physician).
- Loss of response to standard doses of infliximab (as judged by the treating physician).
- Last infliximab infusion given at least 4 weeks before inclusion.
- For patients with luminal disease, the CDAI should be above 220 points at inclusion.
- For patients with fistulising disease only, at least one draining perianal fistula (confirmed by radiography, MR, ultrasound or physical examination) should be present.
Who cannot join
- Any contraindication to continued infliximab treatment
- Short bowel syndrome
- Bowel resection within 12 weeks of inclusion.
- Current or recent history of severe, progressive, and/or uncontrolled renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, or cerebral disease.
- Pregnancy
- History of alcohol or drug abuse within the prior year
- Patients who do not meet concomitant medication criteria.
- Any other condition, which in the Investigator's judgment would make the patient unsuitable for inclusion in the study.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Denmark8 sites
Dept of Medical Gastroenterology, Ålborg University Hospital
Aalborg, 9000
Dept of Hepatology and Medical Gastroenterology, Århus University Hospital
Aarhus, 8000
Institute for Inflammation Research, Copenhagen University Hospital, Rigshospitalet
Copenhagen, 2100
Esbjerg Hospital
Esbjerg, 6700
Herlev University Hospital
Herlev, 2730
Department of Gastroenterology, Hvidovre University Hospital
Hvidovre, 2650
Department of Medical Gastroenterology, Køge University Hospital
Køge, 4600
Dept of Medical Gastroenterology, Odense University Hospital
Odense, 5000
About this study
To compare treatment outcome in patients with Crohn's disease with secondary loss of response to infliximab (i.e. initial good response follow by loss of response) treated according to current standards based only on clinical features versus treatment based on serum levels of infliximab and anti-infliximab antibody (Ab) status.
- Conditions
- Crohn's Disease
- Being tested
- Measurement of serum infliximab and anti-infliximab antibodies, Treatment according to current standards without knowledge of serum infliximab and anti-infliximab Ab status
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Measurement of serum infliximab and anti-infliximab antibodiesProcedure or surgery
In the intervention group treatment of patients with Crohn's disease with secondary loss of response to infliximab is based on serum infliximab and anti-infliximab Ab levels according to following algorithm:
- Low s-infliximab in the presence of anti-infliximab Ab: Adalimumab 80 mg s.c. followed by 40 mg every 2 weeks.
- Low s-infliximab without anti-infliximab Ab: Infliximab 10 mg/kg i.v. every 8 weeks.
- High s-infliximab without anti-infliximab Ab: Stop infliximab treatment. Review history. Steroids or surgery.
- High s-infliximab in the presence of anti-infliximab Ab: Same as number 3.
Treatment according to current standards without knowledge of serum infliximab and anti-infliximab Ab statusProcedure or surgery
In the control group patients with Crohn's disease with secondary loss of response to infliximab is treated according to current standard of care which is to increase dose of infliximab to 5 mg/kg every 4 weeks without knowledge of serum infliximab levels and anti-infliximab Ab status.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Patients with Crohn's disease with secondary loss of response to infliximab. Receives: Procedure: Measurement of serum infliximab and anti-infliximab antibodies |
| 2 | Active comparator | Patients with Crohn's disease with secondary loss of response to infliximab. Receives: Procedure: Treatment according to current standards without knowledge of serum infliximab and anti-infliximab Ab status |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with response at week 12, i.e. CDAI decrease of 70 or more for patients with luminal disease, or reduction of 50 percent or more from base line in the number of draining fistulas for patients with fistulising disease.
Clinical response rates at week 12 should be non-inferior in the intervention group as compared to the control group.
Both primary end-points should be met in order to declare the primary end-points succesfully archived.
Measured: 12 weeks
Total expenses related to Crohn's disease during the study (inclusion to week 12).
Crohn related expenses at week 12 should be less in the intervention group as compared to the control group.
Both primary end-points should be met in order to declare the primary end-points succesfully archived.
Measured: 12 weeks
Secondary outcomes (10)
Mean change compared to baseline in WPAI score at week 12.
Measured: 12 weeks
Mean change compared to baseline in IBDQ score at week 12.
Measured: 12 weeks
Mean change compared to baseline in CDAI score at week 4,8, 12,20.
Measured: 4, 8, 12, 20 weeks
Mean change compared to baseline in PDAI score at week 4, 8, 12, and 20.
Measured: 4, 8, 12, 20 weeks
Clinical response at week 4, 8, 20
Clinical response is defined as decrease of 70 in CDAI (luminal disease) or 50% reduction of active fistulas (fistulizing disease).
Measured: Week 4, 8, 20
Laboratory parameters
Change in laboratory parameters (hemoglobin, crp, albumin) from inclusion to week 12.
Measured: Week 12
Days with subjective feeling of disability due to Crohn's disease
Total number of days with subjective feelinhg of disability due to Crohn's disease from inclusion to week 12.
Measured: week 12
Serious adverse drug reactions
Total number of serious adverse drug reactions from inclusion to week 12.
Measured: week 12
Expenses related to Crohn's diseae at week 20
Measured: week 20
Expenses related to Crohn's disease compared to change in CDAI-score (luminal disease) or PDAI-score (fistulizing disease), and IBD-score at week 12 and 20
Measured: week 12 and 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2009 (estimated)
- Study startJun 2009
- Primary completionFeb 2012 (estimated)
- Study completionFeb 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Crohn's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital at Herlev
- Sponsor type
- University, hospital or other
- Collaborators
- Aase and Ejnar Danielsens Foundation, Beckett Foundation, the Danish Biotechnology Program, Colitis-Crohn Foreningen, Danish Medical Association, Frode V. Nyegaard and wife's Foundation, Health Science Research Foundation of Region of Copenhagen, Herlev Hospital Research Council, Lundbeck Foundation, P. Carl Petersens Fund, Biomonitor A/S, Prometheus Inc., The Danish Institute for Health Services Research
- Investigators
- Mark Ainsworth, M.D., Ph.D. DMSci, Principal investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00851565
- Sponsor's protocol ID
- 01MA
- Status last verified
- Nov 2011
- First submitted
- 24 Feb 2009
- Last updated
- 28 Nov 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ainsworth MA, Bendtzen K, Brynskov J. Tumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease. Am J Gastroenterol. 2008 Apr;103(4):944-8. doi: 10.1111/j.1572-0241.2007.01638.x. Epub 2007 Nov 19.
PubMed 18028512Bendtzen K, Ainsworth M, Steenholdt C, Thomsen OO, Brynskov J. Individual medicine in inflammatory bowel disease: monitoring bioavailability, pharmacokinetics and immunogenicity of anti-tumour necrosis factor-alpha antibodies. Scand J Gastroenterol. 2009;44(7):774-81. doi: 10.1080/00365520802699278.
PubMed 19140087Bendtzen K, Geborek P, Svenson M, Larsson L, Kapetanovic MC, Saxne T. Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab. Arthritis Rheum. 2006 Dec;54(12):3782-9. doi: 10.1002/art.22214.
PubMed 17133559Svenson M, Geborek P, Saxne T, Bendtzen K. Monitoring patients treated with anti-TNF-alpha biopharmaceuticals: assessing serum infliximab and anti-infliximab antibodies. Rheumatology (Oxford). 2007 Dec;46(12):1828-34. doi: 10.1093/rheumatology/kem261.
PubMed 18032541Steenholdt C, Brynskov J, Thomsen OO, Munck LK, Christensen LA, Pedersen G, Kjeldsen J, Ainsworth MA. Implications of Infliximab Treatment Failure and Influence of Personalized Treatment on Patient-reported Health-related Quality of Life and Productivity Outcomes in Crohn's Disease. J Crohns Colitis. 2015 Nov;9(11):1032-42. doi: 10.1093/ecco-jcc/jjv139. Epub 2015 Aug 5.
PubMed 26245216Steenholdt C, Bendtzen K, Brynskov J, Thomsen OO, Munck LK, Christensen LA, Pedersen G, Kjeldsen J, Ainsworth MA. Changes in serum trough levels of infliximab during treatment intensification but not in anti-infliximab antibody detection are associated with clinical outcomes after therapeutic failure in Crohn's disease. J Crohns Colitis. 2015 Mar;9(3):238-45. doi: 10.1093/ecco-jcc/jjv004. Epub 2015 Jan 9.
PubMed 25576753Steenholdt C, Brynskov J, Thomsen OO, Munck LK, Fallingborg J, Christensen LA, Pedersen G, Kjeldsen J, Jacobsen BA, Oxholm AS, Kjellberg J, Bendtzen K, Ainsworth MA. Individualised therapy is more cost-effective than dose intensification in patients with Crohn's disease who lose response to anti-TNF treatment: a randomised, controlled trial. Gut. 2014 Jun;63(6):919-27. doi: 10.1136/gutjnl-2013-305279. Epub 2013 Jul 22.
PubMed 23878167
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Combined Measurements of Serum Infliximab and Anti-infliximab Antibodies in the Treatment of Patients With Crohns Disease Failing Infliximab Therapy
- ClinicalTrials.gov ID
- NCT00851565
- Acronym / sponsor ID
- 01MA
- Conditions
- Crohn's Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Copenhagen University Hospital at HerlevUniversity, hospital or other
- Collaborators
- Aase and Ejnar Danielsens Foundation, Beckett Foundation, the Danish Biotechnology Program, Colitis-Crohn Foreningen, Danish Medical Association, Frode V. Nyegaard and wife's Foundation, Health Science Research Foundation of Region of Copenhagen, Herlev Hospital Research Council, Lundbeck Foundation, P. Carl Petersens Fund, Biomonitor A/S, Prometheus Inc., The Danish Institute for Health Services Research
- Study start
- Jun 2009
- Primary completion
- Feb 2012 (estimated)
- Study completion
- Feb 2014 (estimated)
- First posted
- 26 Feb 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To compare treatment outcome in patients with Crohn's disease with secondary loss of response to infliximab (i.e. initial good response follow by loss of response) treated according to current standards based only on clinical features versus treatment based on serum levels of infliximab and anti-infliximab antibody (Ab) status.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Procedure: Measurement of serum infliximab and anti-infliximab antibodiesPatients with Crohn's disease with secondary loss of response to infliximab. |
| 2 | Active comparator | Procedure: Treatment according to current standards without knowledge of serum infliximab and anti-infliximab Ab statusPatients with Crohn's disease with secondary loss of response to infliximab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patient must be able to understand the information given to him/her and give written informed consent.
- Definitive diagnosis of Crohn's disease (confirmed by recent radiological, endoscopic and/or histological evidence according to international criteria) .
- Age minimum 18 years.
- Previous good response to at least 3 doses (5mg/kg) of infliximab (as judged by the treating physician).
- Loss of response to standard doses of infliximab (as judged by the treating physician).
Key exclusion criteria (8 listed)
- Any contraindication to continued infliximab treatment
- Short bowel syndrome
- Bowel resection within 12 weeks of inclusion.
- Current or recent history of severe, progressive, and/or uncontrolled renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, or cerebral disease.
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Measurement of serum infliximab and anti-infliximab antibodiesIn the intervention group treatment of patients with Crohn's disease with secondary loss of response to infliximab is based on serum infliximab and anti-infliximab Ab levels according to following algorithm: 1. Low s-infliximab in the presence of anti-infliximab Ab: Adalimumab 80 mg s.c. followed by 40 mg every 2 weeks. 2. Low s-infliximab without anti-infliximab Ab: Infliximab 10 mg/kg i.v. every 8 weeks. 3. High s-infliximab without anti-infliximab Ab: Stop infliximab treatment. Review history. Steroids or surgery. 4. High s-infliximab in the presence of anti-infliximab Ab: Same as number 3. | Procedure or surgery | 1 |
| Treatment according to current standards without knowledge of serum infliximab and anti-infliximab Ab statusIn the control group patients with Crohn's disease with secondary loss of response to infliximab is treated according to current standard of care which is to increase dose of infliximab to 5 mg/kg every 4 weeks without knowledge of serum infliximab levels and anti-infliximab Ab status. | Procedure or surgery | 2 |
Primary outcome
Proportion of patients with response at week 12, i.e. CDAI decrease of 70 or more for patients with luminal disease, or reduction of 50 percent or more from base line in the number of draining fistulas for patients with fistulising disease.
Time frame: 12 weeks
Clinical response rates at week 12 should be non-inferior in the intervention group as compared to the control group. Both primary end-points should be met in order to declare the primary end-points succesfully archived.
Total expenses related to Crohn's disease during the study (inclusion to week 12).
Time frame: 12 weeks
Crohn related expenses at week 12 should be less in the intervention group as compared to the control group. Both primary end-points should be met in order to declare the primary end-points succesfully archived.
10 secondary outcomes
Mean change compared to baseline in WPAI score at week 12.
Time frame: 12 weeks
Mean change compared to baseline in IBDQ score at week 12.
Time frame: 12 weeks
Mean change compared to baseline in CDAI score at week 4,8, 12,20.
Time frame: 4, 8, 12, 20 weeks
Mean change compared to baseline in PDAI score at week 4, 8, 12, and 20.
Time frame: 4, 8, 12, 20 weeks
Clinical response at week 4, 8, 20
Time frame: Week 4, 8, 20
Laboratory parameters
Time frame: Week 12
Days with subjective feeling of disability due to Crohn's disease
Time frame: week 12
Serious adverse drug reactions
Time frame: week 12
Expenses related to Crohn's diseae at week 20
Time frame: week 20
Expenses related to Crohn's disease compared to change in CDAI-score (luminal disease) or PDAI-score (fistulizing disease), and IBD-score at week 12 and 20
Time frame: week 12 and 20
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2011.
- Background: PubMed 18028512Ainsworth MA, Bendtzen K, Brynskov J. Tumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease. Am J Gastroenterol. 2008 Apr;103(4):944-8. doi: 10.1111/j.1572-0241.2007.01638.x. Epub 2007 Nov 19.
- Background: PubMed 19140087Bendtzen K, Ainsworth M, Steenholdt C, Thomsen OO, Brynskov J. Individual medicine in inflammatory bowel disease: monitoring bioavailability, pharmacokinetics and immunogenicity of anti-tumour necrosis factor-alpha antibodies. Scand J Gastroenterol. 2009;44(7):774-81. doi: 10.1080/00365520802699278.
- Background: PubMed 17133559Bendtzen K, Geborek P, Svenson M, Larsson L, Kapetanovic MC, Saxne T. Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab. Arthritis Rheum. 2006 Dec;54(12):3782-9. doi: 10.1002/art.22214.
- Background: PubMed 18032541Svenson M, Geborek P, Saxne T, Bendtzen K. Monitoring patients treated with anti-TNF-alpha biopharmaceuticals: assessing serum infliximab and anti-infliximab antibodies. Rheumatology (Oxford). 2007 Dec;46(12):1828-34. doi: 10.1093/rheumatology/kem261.
- Derived from this study: PubMed 26245216Steenholdt C, Brynskov J, Thomsen OO, Munck LK, Christensen LA, Pedersen G, Kjeldsen J, Ainsworth MA. Implications of Infliximab Treatment Failure and Influence of Personalized Treatment on Patient-reported Health-related Quality of Life and Productivity Outcomes in Crohn's Disease. J Crohns Colitis. 2015 Nov;9(11):1032-42. doi: 10.1093/ecco-jcc/jjv139. Epub 2015 Aug 5.
- Derived from this study: PubMed 25576753Steenholdt C, Bendtzen K, Brynskov J, Thomsen OO, Munck LK, Christensen LA, Pedersen G, Kjeldsen J, Ainsworth MA. Changes in serum trough levels of infliximab during treatment intensification but not in anti-infliximab antibody detection are associated with clinical outcomes after therapeutic failure in Crohn's disease. J Crohns Colitis. 2015 Mar;9(3):238-45. doi: 10.1093/ecco-jcc/jjv004. Epub 2015 Jan 9.
- Derived from this study: PubMed 23878167Steenholdt C, Brynskov J, Thomsen OO, Munck LK, Fallingborg J, Christensen LA, Pedersen G, Kjeldsen J, Jacobsen BA, Oxholm AS, Kjellberg J, Bendtzen K, Ainsworth MA. Individualised therapy is more cost-effective than dose intensification in patients with Crohn's disease who lose response to anti-TNF treatment: a randomised, controlled trial. Gut. 2014 Jun;63(6):919-27. doi: 10.1136/gutjnl-2013-305279. Epub 2013 Jul 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Ainsworth, M.D., Ph.D. DMSci principal investigator
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Measurement of serum infliximab and anti-infliximab antibodies and Treatment according to current standards without knowledge of serum infliximab and anti-infliximab Ab status in people with Crohn's Disease, run by Copenhagen University Hospital at Herlev at 8 sites in Denmark.
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 8 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 28 Nov 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Denmark. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
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?
Proportion of patients with response at week 12, i.e. CDAI decrease of 70 or more for patients with luminal disease, or reduction of 50 percent or more from base line in the number of draining fistulas for patients with fistulising disease. (time frame: 12 weeks). The study lists 2 primary outcomes in all. 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 NCT00851565, which also lists 7 linked publications.
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 28 Nov 2011.