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

Chronic Spontaneous Urticaria Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03907878
• Other study ID #: CQGE031C1301
• Status: Completed
• Phase: Phase 3
• Start date: April 13, 2019
• Est. completion date: January 26, 2022

Study information

• Verified date: September 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: January 26, 2022
• Est. primary completion date: January 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Spontaneous Urticaria
• Chronic Urticaria
• Urticaria

Intervention

Biological:
• Ligelizumab
Liquid in vial

Locations

Country	Name	City	State
Japan	Novartis Investigative Site	Hiroshima
Japan	Novartis Investigative Site	Ichikawa	Chiba
Japan	Novartis Investigative Site	Itabashi-ku	Tokyo
Japan	Novartis Investigative Site	Kobe-shi	Hyogo
Japan	Novartis Investigative Site	Machida-city	Tokyo
Japan	Novartis Investigative Site	Neyagawa	Osaka
Japan	Novartis Investigative Site	Nishinomiya-city	Hyogo
Japan	Novartis Investigative Site	Obihiro	Hokkaido
Japan	Novartis Investigative Site	Sakai	Osaka
Japan	Novartis Investigative Site	Yokohama	Kanagawa
Japan	Novartis Investigative Site	Yokohama	Kanagawa

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	64 weeks
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.	Baseline, Weeks 12, 24, 52, and 64
Secondary	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
Secondary	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
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	Weeks 12, 24, 52, and 64
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.	Weeks 12, 24, 52, and 64
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.	Weeks 12, 24, 52, and 64
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.	Baseline, Weeks 12, 24, 52 and 64
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.	Weeks 12, 24, 52, and 64