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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ligelizumab 120 mg per 1 mL qw4 | Experimental | Subjects received one subcutaneous injection every 4 weeks at 13 visits during the treatment period |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ligelizumab | Biological | Liquid in vial |
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| 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 |
| 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. |
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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:
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.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Ichikawa | Chiba | 272-0033 | Japan | ||
| Novartis Investigative Site |
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| Label | URL |
|---|---|
| A Plain Language Trial Summary is Available at www.novctrd.com | View source |
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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
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Safety Set included all subjects who received at least one dose of study treatment.
66 participants enrolled at 11 sites in Japan
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| ID | Title | Description |
|---|---|---|
| FG000 | Ligelizumab 120 mg Per 1 mL qw4 | Subjects received one subcutaneous injection every 4 weeks at 13 visits from baseline to Week 48 during the treatment period. Last treatment was at week 48; and follow up visits were until week 64. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Period |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 14, 2020 | Oct 11, 2022 |
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| 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)
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
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 |
| Obihiro |
| Hokkaido |
| 080 0013 |
| Japan |
| Novartis Investigative Site | Kobe | Hyōgo | 650-0017 | Japan |
| Novartis Investigative Site | Nishinomiya | Hyōgo | 663-8186 | Japan |
| Novartis Investigative Site | Yokohama | Kanagawa | 221-0825 | Japan |
| Novartis Investigative Site | Yokohama | Kanagawa | 222-0033 | Japan |
| Novartis Investigative Site | Neyagawa | Osaka | 572-0838 | Japan |
| Novartis Investigative Site | Sakai | Osaka | 593-8324 | Japan |
| Novartis Investigative Site | Itabashi-ku | Tokyo | 173-8610 | Japan |
| Novartis Investigative Site | Machida | Tokyo | 194-0013 | Japan |
| Novartis Investigative Site | Hiroshima | 734-8551 | Japan |
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| Follow-up Period |
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Safety Set (SAF) included all subjects who received at least one dose of study treatment.
Subjects were analyzed according to the study treatment received. Safety Set was used for all safety analyses and also for all efficacy analyses.
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| ID | Title | Description |
|---|---|---|
| BG000 | Ligelizumab 120 mg Per 1 mL qw4 | Subjects received one subcutaneous injection every 4 weeks at 13 visits from baseline to Week 48 during the treatment period. Last treatment was at week 48; and follow up visits were until week 64. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
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| Age, Continuous | Mean | Standard Deviation | Years |
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| Age, Customized | Age Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Safety Set included all subjects who received at least one dose of study treatment. | Posted | Count of Participants | Participants | 64 weeks |
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| Secondary | 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. | Safety Set: The number analyzed per row is the number of subjects from the SAF who had a valid assessment for both baseline and the corresponding post baseline time point. | Posted | Mean | Standard Deviation | Scores on a scale | Baseline, Weeks 12, 24, 52, and 64 |
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| Secondary | HSS7 Change From Baseline Over Time | The HSS has a scale of 0 (none) to 3 (> 12 hives/12 hours): 0 (None)
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. | Safety Set: The number analyzed per row is the number of subjects from the SAF who had a valid assessment for both baseline and the corresponding post baseline time point. | Posted | Mean | Standard Deviation | Scores on a scale | Baseline, Weeks 12, 24, 52, and 64 |
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| Secondary | ISS7 Change From Baseline Over Time | The ISS has a scale of 0 (none) to 3 (severe): 0 None
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. | Safety Set: The number analyzed per row is the number of subjects from the SAF who had a valid assessment for both baseline and the corresponding post baseline time point. | Posted | Mean | Standard Deviation | Scores on a scale | Baseline, Weeks 12, 24, 52, and 64 |
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| Secondary | 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 | Safety Set: The number analyzed per row is the number of subjects from the SAF who had a valid assessment for both baseline and the corresponding post baseline time point. | Posted | Count of Participants | Participants | Weeks 12, 24, 52, and 64 |
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| Secondary | 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. | Safety Set: The number analyzed per row is the number of subjects from the SAF who had a valid assessment for both baseline and the corresponding post baseline time point. | Posted | Count of Participants | Participants | Weeks 12, 24, 52, and 64 |
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| Secondary | 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. | Safety Set: The number analyzed per row is the number of subjects from the SAF who had a valid assessment for both baseline and the corresponding post baseline time point. | Posted | Count of Participants | Participants | Weeks 12, 24, 52, and 64 |
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| Secondary | 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. | Safety Set: The number analyzed per row is the number of subjects from the SAF who had a valid assessment for both baseline and the corresponding post baseline time point. | Posted | Mean | Standard Deviation | Scores on a scale | Baseline, Weeks 12, 24, 52 and 64 |
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| Secondary | 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. | Safety Set: The number analyzed per row is the number of subjects from the SAF who had a valid assessment for both baseline and the corresponding post baseline time point. | Posted | Count of Participants | Participants | Weeks 12, 24, 52, and 64 |
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Adverse Events (AEs) and Serious Adverse Events were collected after signature of the informed consent form until the end of study at 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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | QGE031 120mg | Ligelizumab 120 mg per 1 mL qw4 | 0 | 66 | 0 | 66 | 41 | 66 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Dental caries | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Injection site erythema | General disorders | MedDRA (24.1) | Systematic Assessment |
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| Injection site pain | General disorders | MedDRA (24.1) | Systematic Assessment |
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| Injection site reaction | General disorders | MedDRA (24.1) | Systematic Assessment |
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| Malaise | General disorders | MedDRA (24.1) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (24.1) | Systematic Assessment |
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| Hepatic function abnormal | Hepatobiliary disorders | MedDRA (24.1) | Systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
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| Folliculitis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
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| Oral herpes | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
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| Arthropod bite | Injury, poisoning and procedural complications | MedDRA (24.1) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
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| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (24.1) | Systematic Assessment |
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| Carpal tunnel syndrome | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
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| Hypoaesthesia | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
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| Asteatosis | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
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| Eczema | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
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| Eczema asteatotic | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
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The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | novartis.email@novartis.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 22, 2022 | Oct 11, 2022 | SAP_001.pdf |
| ID | Term |
|---|---|
| D000080223 | Chronic Urticaria |
| ID | Term |
|---|---|
| D014581 | Urticaria |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C000598891 | ligelizumab |
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| >=65 years |
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