Inflammatory Bowel DiseasesNCT03308357
Comparison of the Performance of SB2-Infliximab With Originator Infliximab in the Measure of Serum Concentrations in Serum
An observational study of Inflammatory Bowel Diseases, run by The Alfred.
Trial summary
The measurement of serum concentrations of infliximab (IFX)has now become a routine part of optimal use of that drug. Trough values are used in two situations: (a) reactively where there is loss of response to infliximab - therapeutic concentrations are indicate likely non-response to the drug, whereas low levels are… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Inflammatory Bowel Diseases
- What is being tested?
- Drug assays to measure infliximab
- How many people
- 6 participants
- Where
- No sites listed yet
- Study dates
- Oct 2017to Mar 2018
- Phase
- Observational
- 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients attending the inflammatory bowel disease outpatient clinics at Alfred Health. Healthy controls will be doctors attending the clinic
Who may be able to join
- Crohn's disease and ulcerative colitis, deemed to be in remission or with active disease according to validated clinical scoring indices
- healthy controls
- Adult patients able to give informed consent to participate
Who cannot join
- not meeting inclusion criteria
Trial locations and contacts
No sites are listed yet.
About this study
The measurement of serum concentrations of infliximab (IFX)has now become a routine part of optimal use of that drug. Trough values are used in two situations: (a) reactively where there is loss of response to infliximab - therapeutic concentrations are indicate likely non-response to the drug, whereas low levels are associated with the chance of regaining response by increasing dosage; or (b) proactively, where dose optimisation in the maintenance phase is performed to ensure ongoing efficacy and/or cost-effective use (where high levels lead to reduction in dosage without loss of efficacy).
With the introduction of biosimilar infliximab into clinical practice, it is important to demonstrate that the biosimilar behaves similarly in the assay used as does originator infliximab to which the assays were developed. While unlikely to be different due to identical protein core, such confirmation is needed before such assays can be used in clinical practice with confidence.
Read more
AIMS
- To compare the concentrations of biosimilar IFX (MSD-IFX) with that of originator IFX (orig-IFX) when added to serum form healthy subjects and those with IBD when measured by commonly-used commercial assays.
- To compare the effect of freeze-thawing and storage at 4 oC on concentrations of MSD-IFX.
Read the detailed description
EXPERIMENTAL PLAN Serum This will separated from peripheral blood taken from 2 healthy subjects, 2 patients with ulcerative colitis (one with quiescent and the other with active disease), and 2 patients with Crohn's disease (one with quiescent and the other with active disease). It will be used wither fresh or freshly thawed from serum stored at -20 oC.
Infliximab
Two sources of infliximab will be used:
- Orig-IFX from Janssen
- MSD-IFX from Merck Sharp \& Dome.
Preparation of simulated serum samples Fresh or thawed serum will be spiked with IFX to obtained serum at concentrations of 0, 1, 2, 4, 6, 8, 10, 12, 15 and 20 ug/ml. This range covers that seen in routine practice. These preparations will be used fresh or stored in aliquots at 4 oC or -20 oC.
Assays to be evaluated These commercially-available assay kits have been chosen on the basis that they are commonly used. They will all be used according to manufacturer's recommendations.
- SHIKARI Q-INFLIXI from Matriks Biotech;
- LISA TRACKER Premium from Theradiag;
- Promonitor ELISA kit from Grifols;
- Quantum Blue Infliximab trough level rapid test from Buhlmann. Testing protocol The two IFX molecules will be tested on the same plates in duplicate at the concentrations prepared (as above). One assay plate will be sufficient for sera from 2 individuals. One assay only will be performed on any one day.
For the direct comparisons, 3 ELISA assay kits will be required to assess 6 pairs of IFX-spiked sera. The rapid test will be performed in duplicate in a similar way.
In order to assess the effect of storing at -20 oC followed by freeze-thawing, and storage at 4 oC, sera from two subjects will be prepared at one concentration (7 ug/ml), will tested fresh and then again 7 days later after storage at the two temperatures. This will l be performed with one assay kit only (the one performing the best in the comparative studies if differences in kits emerge).
Analysis The result of MSD-IFX will be compared to those of Orig-IFX by plotting the respective curves of concentrations and visually comparing them for each assay. The percent deviation for each concentration will be calculated. The results will also be compared across assays for each IFX source and then the findings compared.
- Conditions
- Inflammatory Bowel Diseases
- Being tested
- Drug assays to measure infliximab
- Keywords
- drug monitoring
- Medical subject headings
- Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Drug assays to measure infliximabDiagnostic test
See protocol
| Study group | Role | What they receive |
|---|---|---|
| All six subjects | 2 patients with ulcerative colitis; one with active disease and one in remission. 2 patients with Crohn's disease; one with active disease and one in remission. 2 healthly controls. Single blood sample from each participant, serum collected, that serum will be spiked with known concentrations of the originator infliximab and the biosimilar infliximab and then run on a range of assays to measure infliximab drug concentrations Receives: Diagnostic Test: Drug assays to measure infliximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Drug levels of infliximab originator and biosimilar infliximab
Infliximab drug levels will be measured on a range of commercially available drug assays
Measured: Over the study duration (6 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2017
- Study startOct 2017 (estimated)
- Primary completionMar 2018 (estimated)
- Study completionMar 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inflammatory Bowel DiseasesStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Alfred
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Mark Ward, The Alfred
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03308357
- Sponsor's protocol ID
- MSD IIS-57047- GIBSON
- Status last verified
- Oct 2017
- First submitted
- 9 Oct 2017
- Last updated
- 13 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of the Performance of SB2-Infliximab With Originator Infliximab in the Measure of Serum Concentrations in Serum
- ClinicalTrials.gov ID
- NCT03308357
- Acronym / sponsor ID
- MSD IIS-57047- GIBSON
- Conditions
- Inflammatory Bowel Diseases
- Keywords
- drug monitoring
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- The AlfredUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Oct 2017 (estimated)
- Primary completion
- Mar 2018 (estimated)
- Study completion
- Mar 2018 (estimated)
- First posted
- 12 Oct 2017 (actual)
- 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.
The measurement of serum concentrations of infliximab (IFX)has now become a routine part of optimal use of that drug. Trough values are used in two situations: (a) reactively where there is loss of response to infliximab - therapeutic concentrations are indicate likely non-response to the drug, whereas low levels are associated with the chance of regaining response by increasing dosage; or (b) proactively, where dose optimisation in the maintenance phase is performed to ensure ongoing efficacy and/or cost-effective use (where high levels lead to reduction in dosage without loss of efficacy).
With the introduction of biosimilar infliximab into clinical practice, it is important to demonstrate that the biosimilar behaves similarly in the assay used as does originator infliximab to which the assays were developed. While unlikely to be different due to identical protein core, such confirmation is needed before such assays can be used in clinical practice with confidence.
AIMS
- To compare the concentrations of biosimilar IFX (MSD-IFX) with that of originator IFX (orig-IFX) when added to serum form healthy subjects and those with IBD when measured by commonly-used commercial assays.
- To compare the effect of freeze-thawing and storage at 4 oC on concentrations of MSD-IFX.
Detailed description
EXPERIMENTAL PLAN Serum This will separated from peripheral blood taken from 2 healthy subjects, 2 patients with ulcerative colitis (one with quiescent and the other with active disease), and 2 patients with Crohn's disease (one with quiescent and the other with active disease). It will be used wither fresh or freshly thawed from serum stored at -20 oC.
Infliximab
Two sources of infliximab will be used:
- Orig-IFX from Janssen
- MSD-IFX from Merck Sharp \& Dome.
Preparation of simulated serum samples Fresh or thawed serum will be spiked with IFX to obtained serum at concentrations of 0, 1, 2, 4, 6, 8, 10, 12, 15 and 20 ug/ml. This range covers that seen in routine practice. These preparations will be used fresh or stored in aliquots at 4 oC or -20 oC.
Assays to be evaluated These commercially-available assay kits have been chosen on the basis that they are commonly used. They will all be used according to manufacturer's recommendations.
- SHIKARI Q-INFLIXI from Matriks Biotech;
- LISA TRACKER Premium from Theradiag;
- Promonitor ELISA kit from Grifols;
- Quantum Blue Infliximab trough level rapid test from Buhlmann. Testing protocol The two IFX molecules will be tested on the same plates in duplicate at the concentrations prepared (as above). One assay plate will be sufficient for sera from 2 individuals. One assay only will be performed on any one day.
For the direct comparisons, 3 ELISA assay kits will be required to assess 6 pairs of IFX-spiked sera. The rapid test will be performed in duplicate in a similar way.
In order to assess the effect of storing at -20 oC followed by freeze-thawing, and storage at 4 oC, sera from two subjects will be prepared at one concentration (7 ug/ml), will tested fresh and then again 7 days later after storage at the two temperatures. This will l be performed with one assay kit only (the one performing the best in the comparative studies if differences in kits emerge).
Analysis The result of MSD-IFX will be compared to those of Orig-IFX by plotting the respective curves of concentrations and visually comparing them for each assay. The percent deviation for each concentration will be calculated. The results will also be compared across assays for each IFX source and then the findings compared.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All six subjects | – | Diagnostic Test: Drug assays to measure infliximab2 patients with ulcerative colitis; one with active disease and one in remission. 2 patients with Crohn's disease; one with active disease and one in remission. 2 healthly controls. Single blood sample from each participant, serum collected, that serum will be spiked with known concentrations of the originator infliximab and the biosimilar infliximab and then run on a range of assays to measure infliximab drug concentrations |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients attending the inflammatory bowel disease outpatient clinics at Alfred Health. Healthy controls will be doctors attending the clinic
Key inclusion criteria (3 listed)
- Crohn's disease and ulcerative colitis, deemed to be in remission or with active disease according to validated clinical scoring indices
- healthy controls
- Adult patients able to give informed consent to participate
Key exclusion criteria (1 listed)
- not meeting inclusion criteria
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 |
|---|---|---|
| Drug assays to measure infliximabSee protocol | Diagnostic test | All six subjects |
Primary outcome
Drug levels of infliximab originator and biosimilar infliximab
Time frame: Over the study duration (6 months)
Infliximab drug levels will be measured on a range of commercially available drug assays
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2017.
- Individual participant dataSharing planned: No
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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.
Questions about this trial
What is this clinical trial studying?
An observational study of Inflammatory Bowel Diseases, run by The Alfred.
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 3 inclusion and 1 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 13 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
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.
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?
Contact Mark G Ward, MBBS FRACP MD (+61390762223, m.ward@alfred.org.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Drug levels of infliximab originator and biosimilar infliximab (time frame: Over the study duration (6 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Oct 2017.