The primary objective of this study is to assess the negative predictive value of a Skin Prick Test protocol in subjects with clinical CMA and/or RA.
ID
Source
Brief title
Condition
- Allergic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Reactivity by both skin test procedures and severity of adverse events (AEs)
following subcutaneous challenge.
Number of subjects who experienced a positive skin reaction, as measured by a >=
3-mm wheal over the negative control (SPT) and/or an erythema that equals or
exceeds in mean diameter the positive control (ICT).
Endpoint will be evaluated by recording local reactions and systemic symptoms
of type I hypersensitivity. The negative predictive value of the skin test
protocol will be assessed as the number of subjects without systemic reaction
upon subcutaneous challenge over the number of subjects having tested negative
for the SPT and ICT.
Secondary outcome
NVT
Background summary
Ruconest has been approved for the treatment of acute HAE attacks, a rare
genetic disorder typified by a deficiency or dysfunction of the plasmatic
protein C1INH. 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 HRI, i.e. rabbit
milk proteins or fragments there-off.
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 cow*s 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. The current population is relevant since it has
the highest risk for allergic reactions to Ruconest. So if this study shows
that Ruconest is safe for this specific group, this significantly adds to the
safety profile of the drug for the total population.
Study objective
The primary objective of this study is to assess the negative predictive value
of a Skin Prick Test protocol in subjects with clinical CMA and/or RA.
Study design
Subjects with clinical CMA and/or RA defined by a suggestive history of
symptoms after exposure to cow*s milk and/or rabbit dander and sensitization,
will be contacted for participation in the study. Subjects will attend the
clinic for 3-3.5 hours to undergo 1) confirmation of sensitization by SPT with
cow*s milk and/or rabbit dander 2) SPT with increasing concentrations of
Ruconest, and 3) intracutaneous skin testing (ICT) with increasing
concentrations of Ruconest, 4) 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
Intervention
SPT, ICT, and subcuteanous test with Ruconest
Study burden and risks
Subjects will need to attend the clinic for approximately 14 hours. On the
first testing day, during the skin tests, local allergic reactions may occur,
which can be treated symptomatically with oral antihistamines. Systemic
hypersensitivity reactions are unlikely, and if they might occur can be treated
with systemic antihistamines, steroids and/or epinephrine. At the second
testing day, the subcutaneous challenge visit, systemic hypersensitivity
reactions are possible, which can be treated with systemic antihistamines
(oral, intramuscular, intravenous), steroids (oral, intramuscular, intravenous)
and or epinephrine (intramuscular). These subjects will have no direct benefit
from the study. The current study population is relevant since it has the
highest risk for allergic reactions to Ruconest. So, if this study shows that
Ruconest is safe for this specific group, this significantly adds to the safety
profile of the drug for the total population
Darwinweg 24
Leiden 2333 CR
NL
Darwinweg 24
Leiden 2333 CR
NL
Listed location countries
Age
Inclusion criteria
• Positive SPT and/or IgE >0.35 for CM and/or positive SPT and/or IgE >0.35 for rabbit dander
• Signed written informed consent
• Males and females between 18 and 65 years old
• Medical records documenting clinical CMA and/or RA or suggestive history of symptoms
• Physical examination findings within normal limits
• Willingness and ability to comply with all protocol procedures
Exclusion criteria
• Pregnancy or breastfeeding, or current intention to become pregnant
• Severe dermographism
• Other concurrent disease or condition that would interfere, or for which the treatment might interfere with the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to individuals in this study
• Treatment with drugs that interfere with skin test response
• History or symptoms of significant psychiatric disease, including depression and schizophrenia
• Known or suspected addiction to drug and/or alcohol abuse
• Participation in an investigational drug or device trial within the last 30 days prior to screening
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 |
|---|---|
| EudraCT | EUCTR2011-004048-23-NL |
| CCMO | NL37955.041.11 |