A multi-center, double-blinded and open-label extension study to evaluate the efficacy and safety of ligelizumab as retreatment, self-administered therapy and monotherapy in Chronic Spontaneous Urticaria patients who completed studies CQGE031C2302, CQGE031C2303, CQGE031C2202 or CQGE031C1301

Ligelizumab (QGE031) is a newer humanized immunoglobulin G (IgG)-type
monoclonal antibody that binds to human IgE with higher affinity than
omalizumab. Upon binding to specific epitopes in the C3 region of IgE,
ligelizumab is able to block the interaction of IgE with both the high and low
affinity IgE receptors (Fc*RI and Fc*RII). IgE plays a role in allergic
reactions. The purpose of this extension study (up to 104 weeks of treatment
and up to 52 weeks of posttreatment follow-up) is to establish efficacy and
safety of ligelizumab (QGE031) 120 mg s.c. (every 4 weeks).

The purpose of the study is to establish the efficacy and safety of ligelizumab
in treating adult and adolescent subjects with chronic spontaneous urticaria.

This study also looks how:
• further treatment of ligelizumab works following ligelizumab or omalizumab
treatment in the preceding studies.
• self-administration of ligelizumab works outside of the clinic setting.
• ligelizumab works without the background medication (in a small group of
participants)
• if treatment for a longer time with ligelizumab results in improvement or
recovery of the disease.

This is a phase III multi-center, double-blinded and open-label extension
study. As depicted in Figure 3-1, page 21 of the protocol, the study consists
of 5 distinct periods.
• Screening period, duration 1 to 4 weeks;
• First observation period, duration up to 36 weeks;
• Treatment period, duration of 2 years (104 weeks);
• Second observation period, duration up to 52 weeks;
• Post-treatment follow-up period, duration of 12 weeks or 52 weeks.

The minimum duration of a subject*s stay in the study without early
discontinuation is approximately 37 weeks: 1 week screening plus 36 weeks in
first observation period until the subject exists the study without a relapse.

The maximum duration of a subject*s stay in the study without early
discontinuation is approximately 208 weeks: 4 weeks screening, 36 weeks in
first observation period, 52 weeks in first half of the treatment period, 52
weeks in the second half of the observation period, 52 weeks in second half of
the treatment period and 12 weeks in the follow-up period until the subject
exists the study.

For subjects rolling over from the core study CQGE031C2303 (NLD)

Blinded treatment period (Week 0, 4 and 8):
* Ligelizumab 120 mg arm: 1 injection of 1.0 mL ligelizumab (120 mg/mL) s.c. q4w
* Ligelizumab 72 mg arm: 1 injection of 0.6 mL ligelizumab (120 mg/mL) vial
s.c. q4w
Open-label treatment period (Week 12 through Week 52):
* Ligelizumab 120 mg arm: 1 pre-filled syringe injection of 1.0 mL ligelizumab
s.c. q4w

• s.c. injectie every 4 weken
• Physical examination
• Length (only for participants < 18) and weight measurments
• Blood tests
• Optional blood tests for biomarkers (only for participants 18 years and
older)
• Urine sampling (for female participants pregnancy tests)
• Stool evaluation
• eDiary completion (2x a day)
• Questionnaires
• Electrocariogram

See protocol page 56-65 for the full schedule of assessment in the 5 distinct
periods of the study. The number of assessements to be completed depends on the
visits the subject completes.