Study to Investigate the Efficacy and Safety of QGE031 in Adolescent Patients With Chronic Spontaneous Urticaria (CSU)

This clinical study was designed to evaluate the pharmacokinetics, safety and efficacy of ligelizumab in children from 12 to \< 18 years of age, with chronic spontaneous urticaria (CSU). The participants were treated with ligelizumab as an add-on therapy to approved doses of H1 antihistamines (H1AH) following the guideline on treatment of CSU.

This was a Phase IIb dose-finding, randomized, double-blind, parallel-group, placebo-controlled, multicenter study in adolescent patients. The study consisted of 3 distinct study periods: Screening, Treatment and Follow-up period.

After the screening period (up to 4 weeks), at Day 1 participants were randomized into one of the three treatment arms in 1:2:1 fashion to ligelizumab high dose (120 mg every four weeks (q4w)) versus ligelizumab low dose (24 mg q4w) versus placebo. During the 24 weeks of treatment period, doses were administered on Day 1 then on weeks 4, 8, 12, 16, and 20 weeks after randomization. Participants randomized to placebo received placebo on Day 1, Weeks 4 and 8; thereafter they received 120 mg ligelizumab (high dose) on Weeks 12, 16 and 20 such that by the end of the study, the same number of participants received ligelizumab high dose as low dose. The treatment period was followed by a treatment-free follow-up period of 16 weeks to a maximum of Week 40.

Eligibility Criteria:
Inclusion Criteria:

* Parent or legal guardian's written informed consent and child's assent, if appropriate, must be obtained before any study related activity or assessment is performed. Of note, if the subject reaches age of consent (age as per local law) during the study, they will also need to sign the corresponding study ICF (Informed Consent Form) at the next study visit.
* Male and female adolescent patients aged ≥ 12 to \<18 years at the time of screening.
* Diagnosis of CSU refractory to approved doses of H1-antihistamines at the time of randomization, as defined by all of the following:

  * The presence of itch and hives for at least 6 consecutive weeks at any time prior to enrollment despite current use of non-sedating H1-antihistamines during this time period
  * UAS7 score (range 0 - 42) ≥ 16 and HSS7 (range 0 - 21) ≥ 8 during 7 days prior to randomization (Day 1)
  * In-clinic UAS ≥ 4 on at least one of the screening visit days or Day 1 or a medical record of the presence of hives (confirmed and documented by a physician); patients must have been on H1-antihistamines for treatment of CSU at the time of in-clinic UAS at screening visit and/or time of the medical record of hives (for at least 3 days prior to the in-clinic UAS or medical record) • Patients must have been on H1-antihistamines for treatment of CSU for at least the 3 consecutive days immediately prior to the first screening visit and must have documented current use on the day of the initial screening visit
  * CSU diagnosis for ≥ 6 months
* Willing and able to complete a daily symptom e-Diary for the duration of the study and adhere to the study visit schedules.
* Demonstration of compliance with the e-Diary: patients should not have had any missing e-Diary entries in the 7 days prior to randomization. Re-screening may be considered.

Exclusion Criteria:

* Clearly defined underlying etiology for chronic urticarias other than CSU. This includes the following:

  * Inducible urticaria: urticaria factitia, cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact-urticaria
  * Diseases with possible symptoms of urticaria or angioedema such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), and hereditary or acquired angioedema (e.g., due to C1 inhibitor deficiency)
* Any other skin disease associated with chronic itching that might confound the study evaluations and results (e.g. atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis etc.)
* Previous exposure to omalizumab
* History of anaphylaxis