Clinical trial NCT03308357: Comparison of the Performance of SB2-Infliximab With Originator Infliximab in the Measure of Serum Concentrations in Serum
Official title: Comparison of the Performance of SB2-Infliximab With Originator Infliximab in the Measure of Serum Concentrations in Serum
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Inflammatory Bowel Diseases
Keywords: drug monitoring
Lead sponsor: The Alfred
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2017-10-12
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients attending the inflammatory bowel disease outpatient clinics at Alfred Health. Healthy controls will be doctors attending the clinic

Brief 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 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

1. 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.
2. 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* not meeting inclusion criteria

Primary outcomes:
measure: Drug levels of infliximab originator and biosimilar infliximab
timeFrame: Over the study duration (6 months)
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References: