A clinical trial to test if Ruconest causes immunological reactions in healthy volunteers who are allergic to cow's milk and/or rabbit.

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.

The study aims to demonstrate if a skin test protocol could

be useful in patients with suspected rabbit allergy to

evaluate whether Ruconest can be administered safely to

these subjects.

Study design:

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.

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.

Visit 1 (week -1/week 0): Screening;

Visit 2 (week 0 or later): Basophil activation test, Skin Prick test (SPT), Intracutaneous Test (ICT);

Visit 2 + 24H: Phone call;

Visit 3 (week 2 or later): Subcutaneous challenge (only if SPT and ICT were negative);

Visit 3 + 24H: Phone call.

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.