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NCT04210843

Study of Efficacy and Safety of Ligelizumab in Chronic Spontaneous Urticaria Patients Who Completed a Previous Study With Ligelizumab

Terminated Phase 3 Results posted Last updated 20 June 2024
What this trial tests

Phase 3 trial testing Ligelizumab in Chronic Spontaneous Urticaria in 1,033 participants. Terminated before completion.

Timeline
8 April 2020
Primary endpoint
1 September 2022
1 September 2022

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment1,033
Start date8 April 2020
Primary completion1 September 2022
Estimated completion1 September 2022
Sites273 locations across Italy, Colombia, Japan, Malaysia, Taiwan, Vietnam, Poland, South Korea

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

12 and older, any sex, with Chronic Spontaneous Urticaria. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Subjects From Core Studies (CQGE031C2302 and CQGE031C2303), Receiving the Same Dose Regimen as in the Core Studies, With Well-controlled Disease (UAS7 ≤ 6) at Week 12 Primary · Week 12 of the extension study

The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity. A minimum of 4 out of 7 daily scores were need

GroupValue95% CI
Ligelizumab 72 mg LIVI -Ligelizumab 120 mg PFS53.548.72 – 58.54
Ligelizumab 120 mg LIVI -Ligelizumab 120 mg PFS57.552.71 – 62.57
Percentage of Subjects From Core Studies (CQGE031C2302 and CQGE031C2303), Receiving the Same Dose Regimen as in the Core Studies, With Completely Controlled Disease (UAS7 =0) at Week 12 Secondary · Week 12 of the extension study

The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity. A minimum of 4 out of 7 daily scores were need

GroupValue95% CI
Ligelizumab 72 mg LIVI -Ligelizumab 120 mg PFS37.331.63 – 43.04
Ligelizumab 120 mg LIVI -Ligelizumab 120 mg PFS41.535.61 – 47.36
Change From Extension Study Baseline in the UAS7 at Week 12 in All Subjects From Core Studies (CQGE031C2302 and CQGE031C2303) Receiving the Same Dose Regimen as in the Core Studies Secondary · Extension study baseline (Week 0), Week 12 of the extension study

The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity. A negative change score from extension study ba

GroupValue95% CI
Ligelizumab 72 mg LIVI -Ligelizumab 120 mg PFS-19.83± 13.12
Ligelizumab 120 mg LIVI -Ligelizumab 120 mg PFS-20.41± 12.94
Change From Extension Study Baseline in the ISS7 at Week 12 in All Subjects From Core Studies (CQGE031C2302 and CQGE031C2303) Receiving the Same Dose Regimen as in the Core Studies Secondary · Extension study baseline (Week 0), Week 12 of the extension study

The Itch Severity Score (ISS) was recorded by the subject twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). A weekly score (ISS7) was derived by adding up the average daily scores of the 7 preceding days. The ISS7 ranged from 0 to 21. A higher ISS7 indicated more severe itching. A negative change score from baseline indicates improvement. A minimum of 4 out of 7 daily scores were needed to calculate the ISS7 values. Otherwise, the weekly score was missing for that week. The absolute change from extension study baseline in the ISS7 at Week 12 in all subjects from core

GroupValue95% CI
Ligelizumab 72 mg LIVI -Ligelizumab 120 mg PFS-9.12± 6.35
Ligelizumab 120 mg LIVI -Ligelizumab 120 mg PFS-9.46± 6.55
Change From Extension Study Baseline in the HSS7 at Week 12 in All Subjects From Core Studies (CQGE031C2302 and CQGE031C2303) Receiving the Same Dose Regimen as in the Core Studies Secondary · Extension study baseline (Week 0), Week 12 of the extension study

The Hive Severity Score (HSS) was recorded by the subject twice daily in their eDiary, on a scale of 0 (none) to 3 (\> 12 hives/12 hours). A weekly score (HSS7) was derived by adding up the average daily scores of the 7 preceding days. The HSS7 ranged from 0 to 21 A higher HSS7 indicated a greater number of hives. A negative change score from baseline indicates improvement. A minimum of 4 out of 7 daily scores were needed to calculate the HSS7 values. Otherwise, the weekly score was missing for that week. The absolute change from extension study baseline in the HSS7 at Week 12 in all subject

GroupValue95% CI
Ligelizumab 72 mg LIVI -Ligelizumab 120 mg PFS-10.71± 7.50
Ligelizumab 120 mg LIVI -Ligelizumab 120 mg PFS-10.95± 7.11
Cumulative Number of Angioedema-free Weeks (AAS7=0) up to Week 12 in All Subjects From Core Studies (CQGE031C2302 and CQGE031C2303) Receiving the Same Dose Regimen as in the Core Studies Secondary · From extension study baseline (Week 0) up to Week 12 of the extension study

The Weekly angioedema activity score (AAS) is a validated tool to assess occurrence of episodes of angioedema. If the subject reported the occurrence of angioedema ("opening question") with "no", AAS score for this day was 0. If "yes" was the answer to the opening question, the subject continued to answer questions about the duration, severity and impact on daily functioning and appearance of the angioedema. A score between 0 and 3 was assigned to every answer field. The AAS7 was the weekly sum of the daily AAS. AAS7 scores ranged from 0-105. Higher score indicated more severe disease. AAS7 i

GroupValue95% CI
Ligelizumab 72 mg LIVI -Ligelizumab 120 mg PFS9.30± 0.25
Ligelizumab 120 mg LIVI -Ligelizumab 120 mg PFS9.68± 0.27
Percentage of Subjects From Core Studies (CQGE031C2302 and CQGE031C2303), Receiving the Same Dose Regimen as in the Core Studies, With DLQI = 0-1 at Week 12 Secondary · Week 12 of the extension study

The Dermatology Life Quality Index (DLQI) is a 10-item dermatology-specific quality of life (QoL) measure. Subjects rated their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives thinking about the previous 7 days. An overall score was calculated and ranged from 0 to 30. Higher scores indicated worse disease-related QoL. A DLQI score of 0 or 1 indicated that there was no impact of a skin disease on the patient's life. The percentage of subjects from core studies (CQGE031C2302 and CQGE031C2303) receiving the same dose regimen as in the core stu

GroupValue95% CI
Ligelizumab 72 mg LIVI -Ligelizumab 120 mg PFS45.639.66 – 51.52
Ligelizumab 120 mg LIVI -Ligelizumab 120 mg PFS55.849.77 – 61.79
Percentage of Subjects With Well-controlled Disease (UAS7 ≤ 6) 12 Weeks After Starting Self-administration Secondary · Week 24 of the extension study

The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity. A minimum of 4 out of 7 daily scores were need

GroupValue95% CI
Ligelizumab 72 mg LIVI -Ligelizumab 120 mg PFS69.460.86 – 77.07
Ligelizumab 120 mg LIVI -Ligelizumab 120 mg PFS69.564.40 – 74.21
Percentage of Subjects From Core Studies (CQGE031C2302 and CQGE031C2303), Receiving the Same Dose Regimen as in Core Studies and Who Achieved UAS7≤ 6 at Week 12 in Core Studies, With Well-controlled Disease (UAS7 ≤ 6) at Week 12 of the Extension Study Primary · Week 12 of the extension study

The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals and the intensity of the pruritus over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity. A minimum of 4 out of 7 daily scores were needed to calculate

GroupValue95% CI
Ligelizumab 72 mg LIVI -Ligelizumab 120 mg PFS81.974.73 – 87.92
Ligelizumab 120 mg LIVI -Ligelizumab 120 mg PFS82.675.45 – 88.44

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment-emergent AEs (TEAEs) were assessed from first dose to 16 weeks post-last dose of each period (below): TRT1A: Within the first 12 weeks of treatment (or up to 16 weeks post-last dose if treatment discontinued), up to 0.5 year. TRT1B: From Week 12 to 52 of treatment (or 16 weeks post-last dose if treatment discontinued), up to 1.1 years. TRT2: From Week 52 to 104 of treatment (or 16 weeks post-last dose if treatment discontinued), up to 1.3 years. Entire study: up to 2.5 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

TRT1A Ligelizumab 72 mg LIVI-ligelizumab 120 mg PFS
Serious: 1/288 (0%)
Deaths: 0/288
TRT1A Ligelizumab 120 mg LIVI-ligelizumab 120 mg PFS
Serious: 10/745 (1%)
Deaths: 0/745
TRT1A Total
Serious: 11/1033 (1%)
Deaths: 0/1033
TRT1B Ligelizumab 72 mg LIVI - Ligelizumab 120 mg PFS
Serious: 5/263 (2%)
Deaths: 0/263
TRT1B Ligelizumab 120 mg LIVI - Ligelizumab 120 mg PFS
Serious: 32/684 (5%)
Deaths: 3/684
TRT1B Total
Serious: 37/947 (4%)
Deaths: 3/947
TRT2 Ligelizumab 72 mg LIVI - Ligelizumab 120 mg PFS
Serious: 2/77 (3%)
Deaths: 0/77
TRT2 Ligelizumab 120 mg LIVI - Ligelizumab 120 mg PFS
Serious: 3/206 (1%)
Deaths: 0/206
TRT2 Total
Serious: 5/283 (2%)
Deaths: 0/283
Entire Study Ligelizumab 72 mg LIVI - Ligelizumab 120 mg PFS
Serious: 8/288 (3%)
Deaths: 0/288
Entire Study Ligelizumab 120 mg LIVI - Ligelizumab 120 mg PFS
Serious: 44/745 (6%)
Deaths: 3/745
Entire Study Total
Serious: 52/1033 (5%)
Deaths: 3/1033

Serious adverse events (50 terms)

ReactionSystemTRT1A Ligelizumab 72 mg LI…TRT1A Ligelizumab 120 mg L…TRT1A TotalTRT1B Ligelizumab 72 mg LI…TRT1B Ligelizumab 120 mg L…TRT1B TotalTRT2 Ligelizumab 72 mg LIV…TRT2 Ligelizumab 120 mg LI…TRT2 TotalEntire Study Ligelizumab 7…Entire Study Ligelizumab 1…Entire Study Total
COVID-19Infections and infestations
DiverticulitisInfections and infestations
NephrolithiasisRenal and urinary disorders
Congestive cardiomyopathyCardiac disorders
Mitral valve incompetenceCardiac disorders
Myocardial ischaemiaCardiac disorders
Meniere's diseaseEar and labyrinth disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
Chest painGeneral disorders
DrowningGeneral disorders
FatigueGeneral disorders
Biliary dilatationHepatobiliary disorders
Cholecystitis acuteHepatobiliary disorders
CholestasisHepatobiliary disorders
HyperbilirubinaemiaHepatobiliary disorders
Anaphylactic reactionImmune system disorders
Chronic tonsillitisInfections and infestations
PeritonitisInfections and infestations
PharyngitisInfections and infestations
PneumoniaInfections and infestations
Animal biteInjury, poisoning and procedural complications
Comminuted fractureInjury, poisoning and procedural complications
Hand fractureInjury, poisoning and procedural complications
Meniscus injuryInjury, poisoning and procedural complications
Other adverse events (4 terms — click to expand)

ReactionSystemTRT1A Ligelizumab 72 mg LI…TRT1A Ligelizumab 120 mg L…TRT1A TotalTRT1B Ligelizumab 72 mg LI…TRT1B Ligelizumab 120 mg L…TRT1B TotalTRT2 Ligelizumab 72 mg LIV…TRT2 Ligelizumab 120 mg LI…TRT2 TotalEntire Study Ligelizumab 7…Entire Study Ligelizumab 1…Entire Study Total
COVID-19Infections and infestations
HeadacheNervous system disorders
NasopharyngitisInfections and infestations
PyrexiaGeneral disorders

Most-reported serious reactions: COVID-19, Diverticulitis, Nephrolithiasis, Congestive cardiomyopathy, Mitral valve incompetence, Myocardial ischaemia, Meniere's disease, Nausea.

Data from ClinicalTrials.gov NCT04210843 adverse events section.

Sponsor's own description

The purpose of this extension study was to establish efficacy and safety of ligelizumab. This was assessed in adult and adolescent chronic spontaneous urticaria (CSU) patients who had completed a preceding ligelizumab study and have relapsed, following treatment in these preceding studies, despite standard of care H1-antihistamine (H1-AH) treatment. This study also fulfilled the Novartis commitment to provide post-trial access to patients who had completed studies: CQGE031C2302 (NCT03580369), CQGE031C2303 (NCT03580356), CQGE031C2202 (NCT03437278) or CQGE031C1301 (NCT03907878).

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Antibodies to watch in 2021.
    Kaplon H, Reichert JM. · · 2021 · cited 215× · PMID 33459118 · DOI 10.1080/19420862.2020.1860476
  2. The rationale for development of ligelizumab in food allergy.
    Wood RA, Chinthrajah RS, Eggel A, Bottoli I, et al · · 2022 · cited 30× · PMID 36185545 · DOI 10.1016/j.waojou.2022.100690
  3. Anti-IgE for the Treatment of Chronic Urticaria.
    Wedi B, Traidl S. · · 2021 · cited 29× · PMID 33628747 · DOI 10.2147/itt.s261416
  4. Current and Emerging Therapies for Chronic Spontaneous Urticaria: A Narrative Review.
    Yosipovitch G, Biazus Soares G, Mahmoud O. · · 2023 · cited 20× · PMID 37386330 · DOI 10.1007/s13555-023-00972-6
  5. Monoclonal Antibodies in Treating Chronic Spontaneous Urticaria: New Drugs for an Old Disease.
    Manti S, Giallongo A, Papale M, Parisi GF, et al · · 2022 · cited 7× · PMID 35956071 · DOI 10.3390/jcm11154453
  6. Comprehensive Assessment of Pharmacokinetics, Pharmacodynamics, and Tolerability of Ligelizumab in Healthy Volunteers and Patients with Chronic Spontaneous Urticaria to Optimize Its Subcutaneous Delivery System.
    Ji Y, Calonder C, Kirsilä T, Burciu A, et al · · 2023 · cited 2× · PMID 37765235 · DOI 10.3390/pharmaceutics15092266

Verify or expand the search:

Other trials of Ligelizumab

Trials testing the same drug.

Other recruiting trials for Chronic Spontaneous Urticaria

Currently open trials in the same condition.

Other Novartis Pharmaceuticals trials

Trials by the same sponsor.

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