Objective: To determine whether serum concentration guided dosing of infliximab is not inferior to standard dosing based on bodyweight in patients with severe sarcoidosis in terms of FVC change at 26 weeks.
ID
Source
Brief title
Condition
- Immune disorders NEC
- Lower respiratory tract disorders (excl obstruction and infection)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Lung function i.e. FVC at 26 weeks.
Secondary outcome
Symptoms, CRP-, ACE-, sIL2R-concentrations at week 0, 14, 26 and 50.
Lung function i.e. FVC and DLCO at week 0, 26 and 50.
Imaging: X-Thorax, HRCT and PET scanning at week 0, 26 and 50.
Endpoints in terms of Quality of Life are measurements obtained with EuroQol 5D
and SF36 questionnaires at week 0, 14, 26 and 50.
Endpoints in terms of fatigue are measurements obtained with Checklist
Individual Strength (CIS) at week 0, 14, 26 and 50.
Safety endpoints such as infusion reactions, infections.
Background summary
Rationale: Sarcoidosis is a granulomatous disease that primarily affects the
lung. Severe cases are treated with infliximab. Problems met in daily clinical
practice are that the optimal infliximab dose in sarcoidosis is not known and
the very high drug cost. This study aims to improve cost effectiveness and
safety.
Study objective
Objective: To determine whether serum concentration guided dosing of infliximab
is not inferior to standard dosing based on bodyweight in patients with severe
sarcoidosis in terms of FVC change at 26 weeks.
Study design
Study design: Randomized, controlled, double blind study with a follow up of
one year.
Intervention
Intervention: The intervention group will receive infliximab 3 mg/kg, week 0
and 2. Based on measured serum concentrations, for every patient a dose, to be
given at week 6, resulting in a concentration within the target window, will be
calculated. Thereafter, patients will receive infliximab every 4 weeks.
Additional dose adjustments will be made based on infliximab serum
concentrations. The control group will receive infliximab at the standard dose
of 5 mg/kg at week 0, 2, 6 and thereafter every 4 weeks.
Study burden and risks
Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: The burden and risks are minimal and consists of
several venipunctures, patients have to fill out questionnaires at 4
timepoints. Patients in the intervention arm will receive lower infliximab
dosages. However, at any time during the study the treating pulmonologist can
indicate that an individual patient must receive the maximal dose of 5 mg/kg
e.g. in case of rapid progression of the disease.
Revenues: It is expected that drug cost will decrease by approximately 2
million Euro*s per year in The Netherlands and drug safety might improve.
Koekoekslaan 1 Koekoekslaan 1
Nieuwegein 3435 CM
NL
Koekoekslaan 1 Koekoekslaan 1
Nieuwegein 3435 CM
NL
Listed location countries
Age
Inclusion criteria
patients diagnosed with sarcoidosis being treated with infliximab or with an indication for infliximab;capability of giving informed consent
Exclusion criteria
vaccination with live viral or bacterial vaccines within the previous 3 months, or with the last dose within the previous 3 months;active or untreated latent tuberculosis (by mantoux-Elispot/TBC-IGRA);serious infections within the last 2 months;serious right ventricular heart failure or cor polmunale;Active hepatitis B;history of allergic reactions to monocolonal antibodies or their fragments;oppotunistic infections with the last 6 months;HIV;transplantation;known malignancy;pregnancy or breastfeeding
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| Other | 9999 |
| EudraCT | EUCTR2014-002224-26-NL |
| CCMO | NL49562.100.14 |