A Safety and Efficacy Study of Ligelizumab in the Treatment of CSU in Japanese Patients Inadequately Controlled With H1- Antihistamines

A Multi-center, Open-label Study to Investigate the Safety/Tolerability and Efficacy of Ligelizumab (QGE031) in the Treatment of Adult Japanese Patients With Chronic Spontaneous Urticaria (CSU) Inadequately Controlled With H1 Antihistamines

The purpose of this study was to evaluate the safety and efficacy of ligelizumab in adult Japanese subjects with CSU, who remain symptomatic despite treatment with H1-antihistamines (AHs) at locally approved doses.

The study population consisted of 66 male and female subjects aged ≥ 18 years who were diagnosed with CSU and who remained symptomatic despite the use of H1-AH.

This was a Phase III multi-center, open-label, single arm study. There was a screening period of up to 28 days, a 52 week treatment period, and a 12 week post-treatment follow-up period.

Study Overview

• Status: Completed
• Conditions: Chronic Spontaneous Urticaria
• Intervention / Treatment: Biological: Ligelizumab

Detailed Description

This was a Phase III multi-center, open-label, single arm study. The study consisted of 3 distinct periods:

Screening period (Day -28 to Day -14): Subjects who gave informed consent were assessed for eligibility during this period which lasted for up to 4 weeks.

Treatment period (52 weeks): Subjects had site visits every 4 weeks during this period to receive study drug and complete on-site assessments.

Post-treatment follow-up period (12 weeks): Subject had site visits every 4 weeks with the final visit occurring 16 weeks after the last treatment dose. No study treatment was given during the period.

This study was designed to obtain safety data of QGE031 in 66 Japanese CSU patients.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Hiroshima, Japan, 734-8551
    • Novartis Investigative Site
  • Chiba
    • Ichikawa, Chiba, Japan, 272-0033
      • Novartis Investigative Site
  • Hokkaido
    • Obihiro, Hokkaido, Japan, 080 0013
      • Novartis Investigative Site
  • Hyogo
    • Kobe-shi, Hyogo, Japan, 650-0017
      • Novartis Investigative Site
    • Nishinomiya-city, Hyogo, Japan, 663-8186
      • Novartis Investigative Site
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 221-0825
      • Novartis Investigative Site
    • Yokohama, Kanagawa, Japan, 222-0033
      • Novartis Investigative Site
  • Osaka
    • Neyagawa, Osaka, Japan, 572-0838
      • Novartis Investigative Site
    • Sakai, Osaka, Japan, 593-8324
      • Novartis Investigative Site
  • Tokyo
    • Itabashi-ku, Tokyo, Japan, 173-8610
      • Novartis Investigative Site
    • Machida-city, Tokyo, Japan, 194-0013
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study
• Male and female subjects ≥ 18 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 Baseline (Visit 110, Day 1), 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-AH (at locally approved doses) during this time period
  • UAS7 score (range 0-42) ≥ 16 and HSS7 (range 0-21) ≥ 8 during the 7 days prior to baseline (Visit 110, Day 1)
  • Subjects must be on H1-AH at only approved doses for treatment of CSU for starting at Visit 1 (Day -28 to Day -14)
• Willing and able to complete a daily symptom electronic Diary (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 treatments or excipients or to drugs of similar chemical classes (i.e. to murine, chimeric, or human antibodies)

• Subjects having a clearly defined, predominant trigger of their chronic urticaria (CU) (chronic inducible urticaria (CINDU)) including

  - urticaria factitia (symptomatic dermographism), 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 (e.g., 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 enter treatment period and will not be allowed to rescreen
• Any other skin disease associated with chronic itching that might influence in the investigator's opinion the study evaluations and results (e.g. atopic dermatitis, bullous pemphigoid (BP), dermatitis herpetiformis, senile pruritus, etc)
• Prior exposure to ligelizumab
• Any H2 antihistamine, Leukotriene Receptor Antagonist (LTRA) (montelukast or zafirlukast) or H1 antihistamines use at greater than approved dose after Visit 1

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ligelizumab 120 mg per 1 mL qw4; Subjects received one subcutaneous injection every 4 weeks at 13 visits during the treatment period	Biological: Ligelizumab; Liquid in vial; Other Names: QGE031

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of Ligelizumab 120 mg q4w Treatment for 12 Months	Participants with treatment emergent adverse events (AEs) and serious adverse events (SAEs) summary for entire study (64 weeks) An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, temporally associated with the use of a marketed or investigational medicinal product, gene therapy, theragnostic product, or medical device, in patients, clinical-trial subjects, device users, or other persons, whether or not it is considered to be related to or due to the product.	64 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
UAS7 Change From Baseline Over Time	Mean change from baseline in UAS7 score over time is assessed as absolute change from baseline of UAS7 by visit up to end of study. The Urticaria Activity Score (UAS) is the sum of Hive Severity Score (HSS) and Itch Severiry Score (ISS). The HSS has a scale of 0 (none) to 3 (> 12 hives/12 hours). A weekly score (HSS7) is derived by adding up the average daily scores of the preceding 7 days. So the range is 0-21; and negative change = improvement. The ISS also has a scale of 0 (none) to 3 (severe/difficult to tolerate). A weekly score (ISS7) is derived by adding up the average daily scores of the preceding 7 days. Score range is 0-21; and a negative change from baseline indicates improvement. The UAS7 is the sum of the HSS7 score and the ISS7 score, and has a possible range in score of 0-42. A negative change from baseline indicates improvement.	Baseline, Weeks 12, 24, 52, and 64
HSS7 Change From Baseline Over Time	The HSS has a scale of 0 (none) to 3 (> 12 hives/12 hours): 0 (None); (1-6 hives/12 hours); (7-12 hives/12 hours); (> 12 hives/12 hours) A weekly score (HSS7) is derived by adding up the average daily scores of the preceding 7 days. Score range is 0-21; and a negative change indicates improvement.	Baseline, Weeks 12, 24, 52, and 64
ISS7 Change From Baseline Over Time	The ISS has a scale of 0 (none) to 3 (severe): 0 None; Mild (minimal awareness, easily tolerated); Moderate (definite awareness, bothersome but tolerable); Severe (difficult to tolerate) The ISS also has a scale of 0 (none) to 3 (severe/difficult to tolerate). A weekly score (ISS7) is derived by adding up the average daily scores of the preceding 7 days. So the score range of ISS7 is 0-21; and a negative change from baseline indicates improvement.	Baseline, Weeks 12, 24, 52, and 64
Percentage of Participants Who Achieved the Complete UAS7 = 0 Response Over Time	Assessed as the proportion of subjects achieving UAS7 = 0 over time. The UAS7 has a possible range in score of 0-42, and its complete response (complete urticaria control) was defined as UAS7 = 0	Weeks 12, 24, 52, and 64
Percentage of Participants Who Achieved the Complete HSS7 = 0 Response Over Time	The proportion of subjects achieving HSS7 = 0 (complete absence of hives) over time The HSS has a scale of 0 (none) to 3 (> 12 hives/12 hours). A weekly score (HSS7) is derived by adding up the average daily scores of the preceding 7 days. So the range is 0-21; and negative change = improvement.	Weeks 12, 24, 52, and 64
Percentage of Participants Who Achieved the Complete ISS7 = 0 Response Over Time	The ISS also has a scale of 0 (none) to 3 (severe/difficult to tolerate). A weekly score (ISS7) is derived by adding up the average daily scores of the preceding 7 days. Score range is 0-21; and a negative change from baseline indicates improvement.	Weeks 12, 24, 52, and 64
Change From Baseline in the Dermatology Life Quality Index (DLQI)	Assessed by absolute change from baseline of DLQI up to end of study. Score range is from 0-30: 0-1 No effect on patients life 2-5 Small effect on patients life 6-10 Moderate effect on patients life 11-20 Very large effect on patients life 21-30 Extremely large effect on patients life A negative change indicates improvement.	Baseline, Weeks 12, 24, 52 and 64
Percentage of Participants Who Achieved Dermatology Life Quality Index (DLQI) = 0/1 by Visit up to End of Study	Percentage of participants who achieved DLQI = 0/1 by visit up to end of study, assessed by absolute change from baseline of DLQI up to end of study. Score range is from 0-30: 0-1 No effect on patients life 2-5 Small effect on patients life 6-10 Moderate effect on patients life 11-20 Very large effect on patients life 21-30 Extremely large effect on patients life A negative change indicates improvement.	Weeks 12, 24, 52, and 64

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is Available at www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2019
• Primary Completion (Actual): January 26, 2022
• Study Completion (Actual): January 26, 2022

Study Registration Dates

• First Submitted: April 5, 2019
• First Submitted That Met QC Criteria: April 5, 2019
• First Posted (Actual): April 9, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 4, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Japanese; Japan; QGE031; chronic spontaneous urticaria; CSU; Anti-IgE; Ligelizumab
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases; Skin Diseases, Vascular; Chronic Urticaria; Urticaria
• Other Study ID Numbers: CQGE031C1301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No