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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03907878

Enrollment

Registered

2019-04-09

Start date

2019-04-13

Completion date

2022-01-26

Last updated

2025-03-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Spontaneous Urticaria

Keywords

CSU, chronic spontaneous urticaria, Japanese, QGE031, Anti-IgE, Ligelizumab, Japan

Brief summary

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.

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.

Interventions

BIOLOGICALLigelizumab

Liquid in vial

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

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/

Design outcomes

Primary

Measure	Time frame	Description
Safety and Tolerability of Ligelizumab 120 mg q4w Treatment for 12 Months	64 weeks	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.

Secondary

Measure	Time frame	Description
HSS7 Change From Baseline Over Time	Baseline, Weeks 12, 24, 52, and 64	The HSS has a scale of 0 (none) to 3 (\> 12 hives/12 hours): 0 (None) 1. (1-6 hives/12 hours) 2. (7-12 hives/12 hours) 3. (\> 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.
ISS7 Change From Baseline Over Time	Baseline, Weeks 12, 24, 52, and 64	The ISS has a scale of 0 (none) to 3 (severe): 0 None 1. Mild (minimal awareness, easily tolerated) 2. Moderate (definite awareness, bothersome but tolerable) 3. 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.
Percentage of Participants Who Achieved the Complete UAS7 = 0 Response Over Time	Weeks 12, 24, 52, and 64	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
UAS7 Change From Baseline Over Time	Baseline, Weeks 12, 24, 52, and 64	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.
Percentage of Participants Who Achieved the Complete ISS7 = 0 Response Over Time	Weeks 12, 24, 52, and 64	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.
Change From Baseline in the Dermatology Life Quality Index (DLQI)	Baseline, Weeks 12, 24, 52 and 64	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.
Percentage of Participants Who Achieved Dermatology Life Quality Index (DLQI) = 0/1 by Visit up to End of Study	Weeks 12, 24, 52, and 64	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.
Percentage of Participants Who Achieved the Complete HSS7 = 0 Response Over Time	Weeks 12, 24, 52, and 64	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.

Countries

Japan

Participant flow

Recruitment details

66 participants enrolled at 11 sites in Japan

Pre-assignment details

Safety Set included all subjects who received at least one dose of study treatment.

Participants by arm

Arm	Count
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.	66
Total	66

Withdrawals & dropouts

Period	Reason	FG000
Follow-up Period	Adverse Event	3
Follow-up Period	Withdrawal by Subject	3
Treatment Period	Adverse Event	4
Treatment Period	Lack of Efficacy	1
Treatment Period	Protocol Violation	1
Treatment Period	Withdrawal by Subject	5

Baseline characteristics

Characteristic	Ligelizumab 120 mg Per 1 mL qw4
Age, Continuous	46.4 Years STANDARD_DEVIATION 13.18
Age, Customized < 18 years	0 Participants
Age, Customized >=65 years	7 Participants
Age, Customized Between 18 and 65 years	59 Participants
Race/Ethnicity, Customized Asian	66 Participants
Sex: Female, Male Female	53 Participants
Sex: Female, Male Male	13 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 66
other Total, other adverse events	41 / 66
serious Total, serious adverse events	0 / 66

Outcome results

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.

Time frame: 64 weeks

Population: Safety Set included all subjects who received at least one dose of study treatment.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Ligelizumab 120 mg Per 1 mL qw4	Safety and Tolerability of Ligelizumab 120 mg q4w Treatment for 12 Months	Any AEs	53 Participants
Ligelizumab 120 mg Per 1 mL qw4	Safety and Tolerability of Ligelizumab 120 mg q4w Treatment for 12 Months	Treatment-related AEs	11 Participants
Ligelizumab 120 mg Per 1 mL qw4	Safety and Tolerability of Ligelizumab 120 mg q4w Treatment for 12 Months	Severe AEs	0 Participants
Ligelizumab 120 mg Per 1 mL qw4	Safety and Tolerability of Ligelizumab 120 mg q4w Treatment for 12 Months	Moderate AEs	13 Participants
Ligelizumab 120 mg Per 1 mL qw4	Safety and Tolerability of Ligelizumab 120 mg q4w Treatment for 12 Months	Deaths	0 Participants
Ligelizumab 120 mg Per 1 mL qw4	Safety and Tolerability of Ligelizumab 120 mg q4w Treatment for 12 Months	SAEs	0 Participants
Ligelizumab 120 mg Per 1 mL qw4	Safety and Tolerability of Ligelizumab 120 mg q4w Treatment for 12 Months	AEs leading to treatment discontinuation	4 Participants
Ligelizumab 120 mg Per 1 mL qw4	Safety and Tolerability of Ligelizumab 120 mg q4w Treatment for 12 Months	SAEs leading to treatment discontinuation	0 Participants

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.

Time frame: Baseline, Weeks 12, 24, 52 and 64