A phase II, randomized, double-blind, placebo controlled, parallel design, dose ranging, multi-center trial of four levels of exposure of QGE031 s.c. for 16 weeks in subjects aged 18-50 years with peanut allergy (CQGE031A2208)

With peanut allergy only a small quantity of the allergen may result in serious
and potentially life-threatening allergic reactions. The pathology is IgE
mediated. In the US peanut allergy is the most important cause of fatal
allergic reactions. The incidence seems to increase (from 0,4% in 1997 to 1,4%
in 2008).
The only available therapy is strict abstinence of the consumption of peanuts
and peanut protein containing substances. The risk of accidental use is
present, also because of the widespread use of peanut by the food industry and
problems with accurate labeling. According to a 5 year study 50% of
participants 58% of subjects experienced adverse reactions from accidental
peanut exposure despite best efforts at allergen avoidance. In children the
problem is more explicit than in adults.
QGE031 is a humanized monoclonal antibody directed against human IgE and is a
highly potent inhibitor of human IgE binding to the IgE receptor. The level of
IgE onderdrukking is larger compared to previous monoclonal antibodies.
Therefore a more effective desensitization against the allergen is expected.
In this phase II study the effects of 4 doses of QGE031 will be compared to
those of a placebo. The change in sensitivity will be measured by a
double-blind, placebo-controlled food challenge at baseline and after a 16
weeks treatment period.

Primary: To characterize the QGE031 dose response relationship for the increase
in the threshold dose of peanut protein that induces objective hypersensitivity
reactions after treatment.
Secondary (only key parameters): The percentage of patients that experienced an
increase from baseline to the end of treatment period in the threshold dose of
at least 2 steps (or 10 fold) increase in peanut dose; safety and tolerability.

Multicenter randomized double-blind phase II parallel-group placebo-controlled
study.
Randomisation (1:1:1:1:1) to:
• 14 mg QGE031 s.c. every 2 weeks
• 35 mg QGE031 s.c. every 2 weeks
• 98 mg QGE031 s.c. every 2 weeks
• 238 mg QGE031 s.c. every 2 weeks
• Placebo s.c. every 2 weeks.
Screening periode 2-3 weeks. Treatment period 18 weeks. Follow-up period 12
weeks.
Independent DSMB.
Interim-analyse planned, details not yet known (see protocol paragraph 9.8
(page 62).
Approx. 110 patients.

Treatment with 1 of the 4 dosages of QGE031 or placebo.

Risk: Adverse effects of study medication en food challenge test and prick test.
Burden: Study duration 20-32 weeks. 13-18 visits. Duration 1-2 h, except 4
visits of 6-8 h.
Durng 18 weeks every 2 weeks sc injection of study medication (0,1-1,7
ml/injection).
Physical examination 7-9 times.
Blood tests 13 visits, 25-40 ml/occasion.
Optional pharmacogenetic/-genomics blood test (10 ml).
Pregnancy test (if relevant) 4 times.
Screening: stool sample.
ECG 2 times.
Pulmonary function test once.
Food challenge test 2 times (2 consecutive days/test).
Prick test 2 tomes.
Questionnaire 3 times.