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NCT03580369

A Phase III Study of Safety and Efficacy of Ligelizumab in the Treatment of CSU in Adolescents and Adults Inadequately Controlled With H1-antihistamines

Completed Phase 3 Results posted Last updated 24 July 2023
What this trial tests

Phase 3 trial testing Ligelizumab in Chronic Spontaneous Urticaria in 1,072 participants. Completed in 14 June 2022.

Timeline
17 October 2018
Primary endpoint
16 July 2021
14 June 2022

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment1,072
Start date17 October 2018
Primary completion16 July 2021
Estimated completion14 June 2022
Sites161 locations across Colombia, Malaysia, Poland, South Korea, Guatemala, Croatia, Denmark, Russia

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.

Mean Change From Baseline in UAS7 at Week 12 (Multiple Imputation) of Adult Subjects Primary · Baseline, Week 12

The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. Complete UAS7 response is UAS7 = 0. Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (\>12 hives/12 hours). Itch Severity Sc

GroupValue95% CI
Ligelizumab 72 mg-19.368± 0.668
Ligelizumab 120 mg-19.330± 0.660
Omalizumab 300 mg-20.040± 0.663
Placebo-11.366± 1.129
Mean Change From Baseline in UAS7 at Week 12 (Observed Data) of Adolescent Subjects (FAS) Primary · Baseline, Week 12

The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. Complete UAS7 response is UAS7 = 0. Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (\>12 hives/12 hours). Itch Severity Sc

GroupValue95% CI
Ligelizumab 72 mg-17.39± 13.070
Ligelizumab 120 mg-14.64± 14.662
Omalizumab 300 mg-13.84± 15.343
Placebo-12.75± 18.738
Number and Proportion of Subjects With UAS7=0 Response at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) Secondary · Week 12

The Urticaria Activity Score (UAS) is the sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. Complete UAS7 response is defined as UAS7 = 0. No Statistical analysis was planned for adolescent group.

Adults
GroupValue95% CI
Ligelizumab 72 mg102
Ligelizumab 120 mg104
Omalizumab 300 mg116
Placebo8
Adolescents
GroupValue95% CI
Ligelizumab 72 mg3
Ligelizumab 120 mg3
Omalizumab 300 mg0
Placebo1
Mean Change From Baseline in ISS7 at Week 12 (Multiple Imputation) of Adult Subjects (FAS) Secondary · Baseline, Week 12

Improvement of severity of itch assessed as absolute change from baseline in ISS7 score at Week 12 Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate) Negative change from baseline indicates improvement.

GroupValue95% CI
Ligelizumab 72 mg-8.502± 0.305
Ligelizumab 120 mg-8.532± 0.301
Omalizumab 300 mg-8.921± 0.302
Placebo-5.402± 0.514
Mean Change From Baseline in ISS7 at Week 12 (Observed Data) of Adolescent Subjects, (FAS) Secondary · Baseline, Week 12

Improvement of severity of itch assessed as absolute change from baseline in ISS7 score at Week 12 Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate) Negative change from baseline indicates improvement.. No Statistical Analysis was planned for adolescen

GroupValue95% CI
Ligelizumab 72 mg-8.40± 6.779
Ligelizumab 120 mg-6.82± 7.404
Omalizumab 300 mg-5.10± 7.153
Placebo-7.00± 9.899
Number and Proportion of Participants With DLQI Score of 0 - 1 at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) Secondary · Baseline, Week 12

Assessed as percentage of subjects achieving DLQI = 0-1, meaning, no impact on subjects quality of life at Week 12 The Dermatology life Quality Index (DLQI) score range is 0 to 30, with 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life). No statistical anaylsis was planned for adolescent group.

Adults
GroupValue95% CI
Ligelizumab 72 mg133
Ligelizumab 120 mg150
Omalizumab 300 mg147
Placebo22
Adolescents
GroupValue95% CI
Ligelizumab 72 mg3
Ligelizumab 120 mg6
Omalizumab 300 mg2
Placebo1
Cumulative Number of Weeks of AAS7=0 up to Week 12 (Multiple Imputation) of Adult Subjects (FAS) Secondary · Baseline, Week 12

Cumulative number of weeks that subjects achieve AAS7 = 0 responses between baseline and Week 12 Angioedema Activity Score (AAS7) is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity.

GroupValue95% CI
Ligelizumab 72 mg8.568± 0.235
Ligelizumab 120 mg8.912± 0.239
Omalizumab 300 mg8.790± 0.239
Placebo6.475± 0.327
Cumulative Number of Weeks of AAS7=0 up to Week 12 (Observed Data) of Adolescent Subjects (FAS) Secondary · Baseline, Week 12

Cumulative number of weeks that subjects achieve AAS7 = 0 responses between baseline and Week 12 Angioedema Activity Score (AAS7) is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity. No Statistical Analysis was planned.

GroupValue95% CI
Ligelizumab 72 mg6.0± 4.94
Ligelizumab 120 mg7.3± 5.44
Omalizumab 300 mg9.0± 3.50
Placebo11.0± 0.00

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event (AE) monitoring was continued for at least 30 days following the last dose of study treatment or end of study visit (64 weeks), whichever is longer.. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

QGE031 72mg
Serious: 22/316 (7%)
Deaths: 0/316
QGE031 120mg
Serious: 32/324 (10%)
Deaths: 0/324
Omalizumab 300mg
Serious: 23/319 (7%)
Deaths: 0/319
Placebo Only
Serious: 3/109 (3%)
Deaths: 0/109
Transitioned to QGE031 120mg
Serious: 4/102 (4%)
Deaths: 0/102

Serious adverse events (76 terms)

ReactionSystemQGE031 72mgQGE031 120mgOmalizumab 300mgPlacebo OnlyTransitioned to QGE031 120mg
COVID-19Infections and infestations
Intervertebral disc protrusionMusculoskeletal and connective tissue disorders
Anaphylactic reactionImmune system disorders
BronchitisInfections and infestations
COVID-19 pneumoniaInfections and infestations
Urinary tract infectionInfections and infestations
ConcussionInjury, poisoning and procedural complications
Uterine leiomyomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Abortion spontaneousPregnancy, puerperium and perinatal conditions
AngioedemaSkin and subcutaneous tissue disorders
UrticariaSkin and subcutaneous tissue disorders
Acute myocardial infarctionCardiac disorders
Angina pectorisCardiac disorders
Atrial fibrillationCardiac disorders
CardiomyopathyCardiac disorders
Coronary artery occlusionCardiac disorders
Myocardial infarctionCardiac disorders
Dermoid cystCongenital, familial and genetic disorders
VertigoEar and labyrinth disorders
Abdominal adhesionsGastrointestinal disorders
Diverticulum intestinalGastrointestinal disorders
DysphagiaGastrointestinal disorders
GastritisGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
OesophagitisGastrointestinal disorders
Other adverse events (44 terms — click to expand)

ReactionSystemQGE031 72mgQGE031 120mgOmalizumab 300mgPlacebo OnlyTransitioned to QGE031 120mg
HeadacheNervous system disorders
NasopharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
DiarrhoeaGastrointestinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
UrticariaSkin and subcutaneous tissue disorders
Back painMusculoskeletal and connective tissue disorders
Injection site reactionGeneral disorders
Injection site erythemaGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
Injection site painGeneral disorders
COVID-19Infections and infestations
Urinary tract infectionInfections and infestations
DizzinessNervous system disorders
Chronic spontaneous urticariaSkin and subcutaneous tissue disorders
InfluenzaInfections and infestations
Blood creatinine increasedInvestigations
EczemaSkin and subcutaneous tissue disorders
NauseaGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Abdominal painGastrointestinal disorders
ToothacheGastrointestinal disorders
GastroenteritisInfections and infestations
AngioedemaSkin and subcutaneous tissue disorders
Dermatitis contactSkin and subcutaneous tissue disorders
Abdominal pain upperGastrointestinal disorders
FatigueGeneral disorders
Injection site swellingGeneral disorders
SinusitisInfections and infestations
Aspartate aminotransferase increasedInvestigations
SARS-CoV-2 test positiveInvestigations
DysmenorrhoeaReproductive system and breast disorders
AlopeciaSkin and subcutaneous tissue disorders
HypertensionVascular disorders
BronchitisInfections and infestations
RhinitisInfections and infestations
ContusionInjury, poisoning and procedural complications
Ligament sprainInjury, poisoning and procedural complications

Most-reported serious reactions: COVID-19, Intervertebral disc protrusion, Anaphylactic reaction, Bronchitis, COVID-19 pneumonia, Urinary tract infection, Concussion, Uterine leiomyoma.

Data from ClinicalTrials.gov NCT03580369 adverse events section.

Sponsor's own description

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.

Publications & conference data

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

  1. Antibodies to watch in 2022.
    Kaplon H, Chenoweth A, Crescioli S, Reichert JM. · · 2022 · cited 245× · PMID 35030985 · DOI 10.1080/19420862.2021.2014296
  2. Antibodies to watch in 2021.
    Kaplon H, Reichert JM. · · 2021 · cited 215× · PMID 33459118 · DOI 10.1080/19420862.2020.1860476
  3. Fenebrutinib in H<sub>1</sub> antihistamine-refractory chronic spontaneous urticaria: a randomized phase 2 trial.
    Metz M, Sussman G, Gagnon R, Staubach P, et al · · 2021 · cited 95× · PMID 34750553 · DOI 10.1038/s41591-021-01537-w
  4. Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials.
    Maurer M, Ensina LF, Gimenez-Arnau AM, Sussman G, et al · · 2024 · cited 45× · PMID 38008109 · DOI 10.1016/s0140-6736(23)01684-7
  5. 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
  6. A New Generation of Treatments for Itch.
    Fowler E, Yosipovitch G. · · 2020 · cited 30× · PMID 31940047 · DOI 10.2340/00015555-3347
  7. Tracing IgE-Producing Cells in Allergic Patients.
    Eckl-Dorna J, Villazala-Merino S, Campion NJ, Byazrova M, et al · · 2019 · cited 30× · PMID 31466324 · DOI 10.3390/cells8090994
  8. Anti-IgE for the Treatment of Chronic Urticaria.
    Wedi B, Traidl S. · · 2021 · cited 29× · PMID 33628747 · DOI 10.2147/itt.s261416

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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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03580369.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing