A Phase III Study of Safety and Efficacy of Ligelizumab in the Treatment of CSU in Adolescents and Adults Inadequately Controlled With H1-antihistamines
Condition: Chronic Spontaneous Urticaria
MeSH terms: Urticaria; Chronic Urticaria
Intervention: Ligelizumab; Omalizumab; Placebo
Intervention description: Liquid in vial; Lyophilized powder for solution in vial; Liquid in vial
Intervention MeSH terms: Omalizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This was a Phase III multi-center, randomized, double-blind, active- and placebo-controlled, parallel-group study. There was a screening period of up to 28 days, a 52 week double-blind treatment period, and a 12 week post-treatment follow-up period.
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Patients, investigator staff and personnel performing the study assessments remained blinded to the identity of the treatment from the time of randomization until final database lock. The study drug was prepared by an independent unblinded pharmacist (or authorized delegate) and administered by an independent unblinded study drug administrator. Neither the unblinded pharmacist nor the unblinded study drug administrator was involved in any assessments.
Enrollment: 1072.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: Anti-IgE; CSU; chronic spontaneous urticaria; hives severity score; itch severity score; urticaria activity score

Summary:

      The purpose of this study was to establish safety and efficacy of ligelizumab in adolescent
      and adult subjects with Chronic Spontaneous Urticaria (CSU) who remain symptomatic despite
      standard of care treatment by demonstrating better efficacy over omalizumab and over placebo.

      The study population consisted of 1,072 male and female subjects aged ≥ 12 years who were
      diagnosed with CSU and who remained symptomatic despite the use of H1-antihistamines.

      This was a multi-center, randomized, double-blind, active- and placebo-controlled,
      parallel-group study. There was a screening period of up to 28 days, a 52 week double-blind
      treatment period, and a 12 week post-treatment follow-up period.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Signed informed consent must be obtained prior to participation in the study. The
             subject's, parent's or legal guardian's signed written informed consent and child's
             assent, if appropriate, must be obtained before any 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 Informed Consent Form (ICF) at the next
             study visit.

          -  Male and female subjects ≥ 12 years of age at the time of screening.

          -  CSU diagnosis for ≥ 6 months.

          -  Diagnosis of CSU refractory to H1-AH at approved doses at the time of randomization,
             as defined by all of the following:

          -  The presence of itch and hives for ≥ 6 consecutive weeks at any time prior to Visit 1
             (Day - 28 to Day -14) despite current use of non-sedating H1-antihistamine

          -  UAS7 score (range 0-42) ≥ 16 and HSS7 (range 0-21) ≥ 8 during the 7 days prior to
             randomization (Visit 110, Day 1)

          -  Subjects must be on H1-antihistamine at only locally label approved doses for
             treatment of CSU starting at Visit 1 (Day -28 to Day -14)

          -  Willing and able to complete a daily symptom eDiary for the duration of the study and
             adhere to the study visit schedules.

        Key Exclusion Criteria:

          -  History of hypersensitivity to any of the study drugs or their excipients or to drugs
             of similar chemical classes (i.e. to murine, chimeric or human antibodies).

          -  Subjects having a clearly defined cause of their chronic urticaria, other than CSU.
             This includes, but is not limited to, the following: symptomatic dermographism
             (urticaria factitia), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-,
             cholinergic- or contact-urticaria.

          -  Diseases, other than chronic urticaria, with urticarial or angioedema symptoms such as
             urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria
             pigmentosa) and hereditary or acquired angioedema (eg, due to C1 inhibitor
             deficiency).

          -  Subjects with evidence of helminthic parasitic infection as evidenced by stools being
             positive for a pathogenic organism according to local guidelines. All subjects will be
             screened at Visit 1. If stool testing is positive for pathogenic organism, the subject
             will not be randomized and will not be allowed to rescreen.

          -  Any other skin disease associated with chronic itching that might influence in the
             investigators opinion the study evaluations and results (e.g. atopic dermatitis,
             bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.).

          -  Prior exposure to ligelizumab or omalizumab.

          -  H1-AH used as background medication at greater than locally label-approved doses after
             visit 1