|- candidate number||12900|
|- NTR Number||NTR3477|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||15-jun-2012|
|- Secondary IDs||C1 1113 Pharming Technologies BV|
|- Public Title||A clinical trial to test if Ruconest causes immunological reactions in healthy volunteers who are allergic to cow's milk and/or rabbit.|
|- Scientific Title||A Phase I Study to assess in vitro and in vivo immunoreactivity of Ruconest in Subjects with cow's milk allergy (CMA) and/or rabbit allergy (RA).|
|- ACRONYM||Ruconest Skin Prick Test Validation Protocol|
|- hypothesis||A SPT has been proposed to screen subjects with increased risk of hypersensitivity reaction to Ruconest. Subjects with RA and subjects with clinical CMA have an increased risk of hypersensitivity: although cow's milk proteins differ from rabbit milk proteins, cross-reaction between the Ruconest HRIs with cowĄŻs milk IgEs in subjects with clinical CMA, is certainly possible.
Performing the skin testing in subjects with clinical CMA and subjects with RA will evaluate the negative predictive value of a Ruconest skin test protocol in a highly relevant population.|
|- Healt Condition(s) or Problem(s) studied||Cow's milk allergy, Rabbit Allergy (RA)|
|- Inclusion criteria||1. Signed written informed consent;|
2. Males and females between 18 and 65 years old;
3. Medical records documenting clinical CMA and/or RA.
|- Exclusion criteria||1. Pregnancy or breastfeeding;|
2. Severe dermographism;
3. Other concurrent disease or treatment that might interfere with the conduct of the study or the skin test response;
4. History or symptoms of significant psychiatric disease, including depression and schizophrenia or known or suspected addiction to drug and/or alcohol abuse.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||Single arm|
|- planned startdate ||10-apr-2012|
|- planned closingdate||31-dec-2012|
|- Target number of participants||27|
|- Interventions||Ruconest (rhC1INH, recombinant human C1 inhibitor).|
Positive controls: Histamine-dihydrochloride 10 mg/ml (SPT) and histamine-BASE 0.01 mg/mL (ICT).
Negative control: Saline.
|- Primary outcome||Negative predictive value of the Skin Prick Test is defined as the ratio of subjects without systemic symptoms of hypersensitivity following subcutaneous challenge over the number of subjects having tested negative for the SPT and ICT administration.
Number and percent of subjects who experienced a positive skin reaction, defined as a > 3-mm wheal for SPT and/or > 10-mm erythema change from negative control for ICT.
Treatment-emergent adverse events (TEAE) will be summarized by cohort of dilution; TEAEs are defined as adverse events (AEs) not present prior to the start of study product, or AEs present before study product that worsened after starting study product.
|- Secondary outcome||Observation and description of local and/or systemic reactions following SPT, ICT and subcutaneous injection.|
|- Timepoints||Visit 1 (week -1/week 0): Screening;|
Visit 2 (week 0): Basophil activation test, Skin Prick test (SPT), Intracutaneous Test (ICT);
Visit 2 + 24H: Phone call;
Visit 3 (week 2): Subcutaneous challenge (only if SPT and ICT were negative);
Visit 3 + 24H: Phone call.
|- Trial web site||N/A|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES|| Annemarie Kleefstra|
|- CONTACT for SCIENTIFIC QUERIES|| Anurag Relan|
|- Sponsor/Initiator ||University Medical Center Utrecht (UMCU)|
(Source(s) of Monetary or Material Support)
|Pharming Technologies BV|
|- Brief summary||Rationale:|
Ruconest has recently been approved for the treatment of acute attacks of angioedema (HAE), a rare genetic disorder. The active ingredient in Ruconest is a recombinant human protein secreted in the milk of transgenic rabbits expressing the human gene for C1-esterase inhibitor (C1INH). Ruconest contains low levels of host related impurities (HRI) i.e. rabbit milk proteins or fragments.
Subjects will undergo 1) SPT with increasing concentrations of Ruconest, and 2) intracutaneous skin testing (ICT) with increasing concentrations of Ruconest, 3) a blood draw to test basophil activation.
Subjects who tested negatively to the SPT and ICT will be asked to present after two weeks or later for 9-9,5 hours for a subcutaneous challenge with 4 increasing doses with standard solution of Ruconest.
|- Main changes (audit trail)|
|- RECORD||15-jun-2012 - 19-mrt-2013|