Clinical trial NCT03437278: Study to Investigate the Efficacy and Safety of QGE031 in Adolescent Patients With Chronic Spontaneous Urticaria (CSU)
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 2b Dose-finding Study to Investigate the Efficacy and Safety of Ligelizumab (QGE031) in Adolescent Patients With Chronic Spontaneous Urticaria (CSU)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Spontaneous Urticaria
Keywords: Anti-IgE
Chronic spontaneous urticaria
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-02-19
Enrollment: 49
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This was a Phase 2b dose-finding, randomized, double-blind, parallel group, placebo controlled multicenter study in adolescent patients
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Primary outcomes:
measure: Change From Baseline of Weekly Urticaria Activity Score (UAS7) at Week 24
timeFrame: Baseline, week 24
Secondary outcomes:
measure: Change From Baseline of Weekly Urticaria Activity Score (UAS7) at Weeks 12 and 40
timeFrame: Baseline, weeks 12 and 40
measure: Percentage of Participants With Complete Response in Weekly Urticaria Activity Score (UAS7)
timeFrame: Weeks 12, 24 and 40
measure: Change From Baseline of Weekly Itch Severity Score (ISS7)
timeFrame: Baseline, weeks 12, 24 and 40
measure: Percentage of Participants With Complete Response in Weekly Itch Severity Score (ISS7)
timeFrame: Weeks 12, 24 and 40
measure: Change From Baseline of Weekly Hives Severity Score (HSS7)
timeFrame: Baseline, weeks 12, 24 and 40
measure: Percentage of Participants With Complete Response in Weekly Hives Severity Score (HSS7)
timeFrame: Weeks 12, 24 and 40
measure: Change From Baseline of the Children Dermatology Life Quality Index (CDLQI)
timeFrame: Baseline, weeks 12, 24 and 40
measure: Change From Baseline in Total Human Immunoglobulin E (IgE)
timeFrame: Baseline, weeks 12, 24 and 40
measure: Apparent Clearance (CL/F) of Ligelizumab Estimated With a PopPK Model
timeFrame: Weeks 0 (baseline), 4, 8, 12, 16, 20 (all pre-dose) and weeks 24, 32 and 40
measure: Apparent Volume of Distribution of Ligelizumab Estimated With a PopPK Model
timeFrame: Weeks 0 (baseline), 4, 8, 12, 16, 20 (all pre-dose) and weeks 24, 32 and 40
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From the start of treatment to 20 weeks after end of treatment, assessed up to maximum duration of 40 weeks
Other outcomes:
Locations:
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: Bahia Blanca
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
state: HUN
city: New Delhi
country: India
facility: Novartis Investigative Site
state: Delhi
city: Nashik
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Bikaner
country: India
facility: Novartis Investigative Site
state: Rajasthan
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Smolensk
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Esplugues de Llobregat
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Aydin
country: Turkey
facility: Novartis Investigative Site
Study officials:
References: