The aim of this study is to evaluate the AUC, disease status, presence of ADAbs and treatment burden when switching from IV to SC IFX maintenance treatment in a real-world cohort of IBD patients on IFX monotherapy and combination therapy.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacokinetics:
- The first primary endpoint is the AUC at steady state normalized to a period
of 8 weeks. Mean AUC SC CT-P13 will be compared to baseline AUC on IV IFX.
- The second primary endpoint is the AUC of one dose interval at steady state
for SC CT-P13. AUC SC CT-P13 of cohort 1 will be compared to the AUC SC CT-P13
of cohort 2.
Secondary outcome
Pharmacokinetic: IFX trough level
treatment related time expenditure:
- In hospital time
- Travel time
Background summary
In July 2020, the subcutaneous formulation of infliximab (CT-P13, Remsima ®),
which is fixed in a dosing regimen of 120 mg once every 2 weeks after an
induction phase, was approved for all iintravenous infliximab indications in
adults, including Inflammatory Bowel DIsease (IBD). This was decided by the
European Medicines Agency (EMA) on the basis of a non-inferiority study in
patients with rheumatoid arthritis (RA), comparing SC CT-P13 to 3 mg/kg IFX IV
with concomitant methotrexate (MTX).[11] Assumptions regarding indication
extrapolation for SC dosing were that the trough level and the Area Under the
Curve (AUC) were comparable for SC application in both RA and IBD indications.
This includes also comparability for the data on immunogenicity with the SC
administration compared to a historical cohort of patients treated with IV IFX.
Comparability in SC kinetics among IBD and RA patients was confirmed in phase 1
studies (CT-P13 1.6 and CT-P13 3.5) were patients received at least one dose.
In IBD, however, IFX IV is usually given at a dose of 5 mg/kg versus 3 mg/kg in
RA whilst the inflamed surface most commonly is (considerably) larger and in
clinical practice some IBD patients are treated with IFX monotherapy.[11] SC
CT-P13 was approved for IBD by the EMA based on pharmacokinetic comparability
and evaluation on immunogenicity without a head-to-head comparison with IV
IFX, leaving clinicians with several considerations for the application of the
new formulation in practice.
Study objective
The aim of this study is to evaluate the AUC, disease status, presence of ADAbs
and treatment burden when switching from IV to SC IFX maintenance treatment in
a real-world cohort of IBD patients on IFX monotherapy and combination therapy.
Study design
This is a prospective, single centre, open-label cohort study, conducted in
Zuyderland Medical Centre in which IBD patients on stable IV IFX therapy are
switched to SC CT-P13 and is designed to compare the pharmacokinetics of SC
CT-P13 to IV IFX and relate this to the pharmacodynamics. Subjects will be
enrolled into two study cohorts:
• Cohort 1: adult patients on maintenance monotherapy of IV IFX.
• Cohort 2: adult patients on maintenance combination therapy of IV IFX with a
thiopurine derivate or methotrexate.
The study is subdivided into two phases: the IV IFX treatment phase and the SC
CT-P13 treatment phase. After enrolment, the subject received a final dose of
IV IFX according to their own maintenance schedule. The date of the last IV IFX
dose is the start of the individual follow-up period and is referred to as day
0, week 0 (baseline, V1). Subsequently, the first dose of SC CT-P13 will be
administered at the time when the patient would normally receive the next dose
of IV IFX. This will be 6-8 weeks after the last IV infusion and is referred as
day 1, week 1 (V2). Patients are then switched to the standard
self-administered SC dosing regimen of CT-P13.
Study burden and risks
The nature of the risk for participating patients is related to the risks of
venapunction: bleeding of spot of puncture, hematoma formation, infection,
nerve puntion. The patient burden is related to the number of defined moments
for venapunture.
Henri Dunantstraat 5
Heerlen 6419
NL
Henri Dunantstraat 5
Heerlen 6419
NL
Listed location countries
Age
Inclusion criteria
• Adult patients (18-75 years) with an confirmed diagnosis of IBD according to
usual criteria, including previous endoscopic examination.
• Patients on IV IFX maintenance therapy at a stable dose and dosing interval
for at least 16 weeks of 5-10 mg/kg every 6-8 weeks without side effects of IFX.
• IBD in clinical remission for at least 16 weeks without treatment with
systemic corticosteroids in the previous 16 weeks. Clinical remission in adult
patients is defined as a Harvey-Bradshaw index (HBI) < 4 for CD [18] or a
partial Mayo Index (PMI) <2 for UC [19], with faecal calprotectin levels <250
µg/g faeces and CRP <10 mg/L.
• Concomitant immunomodulators are allowed, i.e. in stable doses were received
for at least 12 weeks prior to study enrolment. These doses will be continued
throughout the study, including azathioprine (AZA), 6-mercaptopurine (6-MP),
tioguanine (TG) and MTX.
• Written informed consent
Exclusion criteria
• Patient <18 years of age.
• Allergy or hypersensitivity to any of the excipients of SC CT-P13.
• Patient with active perianal fistula.
• Patient with another autoimmune disease in addition to IBD.
• Patient treated concomitantly with another Mab in addition to IFX.
• Patients who, after starting IV IFX, have developed new contraindications to
IFX according to European Public Assessment Report (EPAR).[3]
• Female patient who is currently pregnant or breastfeeding, or is planning to
become pregnant or breastfeed within 6 months of the last dose of IFX.
• Patient has a serious acute or chronic medical or psychiatric condition that
might increase the risk associated with study participation or investigational
product administration or that might interfere with the interpretation of study
results.
• Patients who, in the opinion of their general practitioner or investigator,
should not participate in the study (e.g. non-adherence, mental health
problems, illiteracy).
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL85721.096.23 |