Back to resultsStudy of Efficacy and Safety of Ligelizumab in Adolescents and Adults With Chronic Inducible Urticaria Who Remain Symptomatic Despite Treatment With H1- Antihistamines (PEARL-PROVOKE)
Primary Purpose
Chronic Inducible Urticaria
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ligelizumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Inducible Urticaria focused on measuring ligelizumab, anti-IgE, CINDU, chronic inducible urticaria, symptomatic dermographism, cold urticaria, cholinergic urticaria, urticaria, itch, hives
Eligibility Criteria
Inclusion Criteria:
Confirmed CINDU diagnosis (as per guidelines) for symptomatic dermographism, cold urticaria or cholinergic urticaria for ≥ 4 months.
- Diagnosis of CINDU (symptomatic dermographism, cold urticaria or cholinergic urticaria) inadequately controlled with H1-AH at local label approved doses at the time of randomization, as defined by all of the following:
- Positive response (i.e development of symptoms) to triggers despite treatment with H1-AH
- Positive response (i.e. development of symptoms) to provocation test on day of randomization
- Participants must be able to physically perform the protocol defined provocation test specific to the participant's CINDU.
- Cholinergic urticaria participants must show sweating in performing the pulse-controlled ergometry test on day of randomization. Participants with anhidrosis must not be included.
- Willing and able to complete a daily symptom eDiary as per protocol requirement and adhere to the study visit schedules
Exclusion Criteria:
History of hypersensitivity to any of the study drugs or its components or to drugs of similar chemical classes or to the provocation test or items used in provocation tests
- Participants who have concomitant CSU at screening
- Participants who have a familial form of the target CINDU that is being considered for the participant's inclusion in this study
- Participants having a more defined other form of inducible urticaria than the target CINDU that is being considered for the participant's inclusion in this study
- Diseases, other than chronic inducible urticaria, with urticarial or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema (eg, due to C1 inhibitor deficiency).
- Any other skin disease associated with chronic itching that might influence, in the investigator's opinion, the study evaluations and results (eg, atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.) or skin diseases associated with only wheals and no itch e.g asymptomatic dermographism
- Prior exposure to ligelizumab, omalizumab and or other anti-IgE therapies
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm Type
Experimental
Experimental
Placebo Comparator
Experimental
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
Ligelizumab low dose, symptomatic dermographism group
Ligelizumab high dose, symptomatic dermographism
Placebo SC q4W, symptomatic dermographism
Ligelizumab low dose, cold urticaria
Ligelizumab high dose, cold urticaria
Placebo SC q4w, cold urticaria
Ligelizumab high dose, cholinergic urticaria
Placebo SC q4w, cholinergic urticaria
Arm Description
Ligelizumab low dose subcutaneous injection every 4 weeks in participants with symptomatic dermographism
Ligelizumab high dose subcutaneous injection every 4 weeks in participants with symptomatic dermographism
Placebo subcutaneous injection every 4 weeks in participants with symptomatic dermographism
Ligelizumab low dose subcutaneous injection every 4 weeks in participants with cold urticaria
Ligelizumab high dose subcutaneous injections every 4 weeks in participants with cold urticaria
Placebo subcutaneous injection every 4 weeks in participants with cold urticaria
Ligelizumab high dose subcutaneous injections every 4 weeks in participants with cholinergic urticaria
Placebo subcutaneous injections every 4 weeks in participants with cholinergic urticaria
Outcomes
Primary Outcome Measures
Change From Baseline in Total Fric Score in Participants With Symptomatic Dermographism
Total Fric score (a scale of 0-4 where 0= no linear hive ≥ 3mm in width, 1= one linear hive ≥ 3mm in width, 2= two linear hives ≥ 3mm in width, 3= three linear hives ≥ 3mm in width and 4 = four linear hives ≥ 3mm in width)
None of the participants completed Week 12 and hence at Week 12 was not analyzed
Change From Baseline in Critical Temperature Threshold in Participants With Cold Urticaria
The TempTest is used to induce itch and hives in participants with cold urticaria. Critical temperature threshold (CTT), as measured by the TempTest, determines the highest temperature sufficient for inducing symptoms.
Change From Baseline in Itch Numerical Rating Scale in Participants With Cholinergic Urticaria
Itch numerical rating scale, a scale from 0 to 10. Negative change from baseline indicates improvement.
Patients were asked to rate itching severity based on the worst level of itching in the past 24 h using an 11-point scale from 0 ("no itch") to 10 ("worst possible itch")
Secondary Outcome Measures
Proportion of Participants With Symptomatic Dermographism With Total Fric Score = 0
Total Fric score (a scale of 0-4 where 0= no linear hive ≥ 3mm in width, 1= one linear hive ≥ 3mm in width, 2= two linear hives ≥ 3mm in width, 3= three linear hives ≥ 3mm in width and 4 = four linear hives ≥ 3mm in width)
None of the participants completed Week 12
Change From Baseline in Itch Numerical Rating Scale in Participants With Symptomatic Dermographism
Itch numerical rating scale, a scale from 0 to 10. Negative change from baseline indicates improvement.
Patients were asked to rate itching severity based on the worst level of itching in the past 24 h using an 11-point scale from 0 ("no itch") to 10 ("worst possible itch")
Proportion of Participants With Cold Urticaria With Complete Response (no Itch or Hives) to the TempTest
The TempTest® is used to induce itch and hives in participants with cold urticaria. Critical temperature threshold (CTT), as measured by the TempTest, determines the highest temperature sufficient for inducing symptoms.
Change From Baseline in Itch Numerical Rating Scale in Participants With Cold Urticaria
Itch numerical rating scale, a scale from 0 to 10. Negative change from baseline indicates improvement.
Patients were asked to rate itching severity based on the worst level of itching in the past 24 h using an 11-point scale from 0 ("no itch") to 10 ("worst possible itch")
Proportion of Participants With Cholinergic Urticaria With Itch Numerical Rating Scale =0
Itch numerical rating scale, a scale from 0 to 10. Negative change from baseline indicates improvement.
Patients were asked to rate itching severity based on the worst level of itching in the past 24 h using an 11-point scale from 0 ("no itch") to 10 ("worst possible itch")
Proportion of Participants With Cholinergic Urticaria With Physician Global Assessment of Severity of Hives (PGA - Hive Score) =0
Physician global assessment of severity of hives
PGA is an assessment of all lesions scored on a scale from 0-5 (with 0 = No hives and 5 = Very severe hives)
Full Information
NCT ID
NCT05024058
First Posted
August 23, 2021
Last Updated
September 11, 2023
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT05024058
Brief Title
Study of Efficacy and Safety of Ligelizumab in Adolescents and Adults With Chronic Inducible Urticaria Who Remain Symptomatic Despite Treatment With H1- Antihistamines
Acronym
PEARL-PROVOKE
Official Title
A Multi-center, Randomized, Double-blind, Placebo Controlled Study to Investigate the Efficacy and Safety of Ligelizumab (QGE031) in the Treatment of Chronic Inducible Urticaria (CINDU) in Adolescents and Adults Inadequately Controlled With H1-antihistamines
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Terminated
Why Stopped
Phase III PEARL studies (CQGE031C2302 and CQGE031C2303) with ligelizumab met their primary endpoint of superiority vs placebo at Week 12 for treatment of CSU, but not versus omalizumab. Decision to discontinue was not based on safety concerns.
Study Start Date
November 16, 2021 (Actual)
Primary Completion Date
August 9, 2022 (Actual)
Study Completion Date
August 9, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This was a placebo controlled, phase 3 study designed to evaluate the efficacy and safety of ligelizumab in participants with chronic inducible urticaria who are inadequately controlled with H1-antihistamines
Detailed Description
There are currently no approved therapies for patients with CINDU who remain symptomatic despite treatment with H1-antihistamines. The purpose of this study was to establish efficacy and safety of ligelizumab (QGE031) over placebo in participants with chronic inducible urticaria (CINDU) who remain symptomatic despite treatment with H1 antihistamine.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Inducible Urticaria
Keywords
ligelizumab, anti-IgE, CINDU, chronic inducible urticaria, symptomatic dermographism, cold urticaria, cholinergic urticaria, urticaria, itch, hives
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
39 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ligelizumab low dose, symptomatic dermographism group
Arm Type
Experimental
Arm Description
Ligelizumab low dose subcutaneous injection every 4 weeks in participants with symptomatic dermographism
Arm Title
Ligelizumab high dose, symptomatic dermographism
Arm Type
Experimental
Arm Description
Ligelizumab high dose subcutaneous injection every 4 weeks in participants with symptomatic dermographism
Arm Title
Placebo SC q4W, symptomatic dermographism
Arm Type
Placebo Comparator
Arm Description
Placebo subcutaneous injection every 4 weeks in participants with symptomatic dermographism
Arm Title
Ligelizumab low dose, cold urticaria
Arm Type
Experimental
Arm Description
Ligelizumab low dose subcutaneous injection every 4 weeks in participants with cold urticaria
Arm Title
Ligelizumab high dose, cold urticaria
Arm Type
Experimental
Arm Description
Ligelizumab high dose subcutaneous injections every 4 weeks in participants with cold urticaria
Arm Title
Placebo SC q4w, cold urticaria
Arm Type
Placebo Comparator
Arm Description
Placebo subcutaneous injection every 4 weeks in participants with cold urticaria
Arm Title
Ligelizumab high dose, cholinergic urticaria
Arm Type
Experimental
Arm Description
Ligelizumab high dose subcutaneous injections every 4 weeks in participants with cholinergic urticaria
Arm Title
Placebo SC q4w, cholinergic urticaria
Arm Type
Placebo Comparator
Arm Description
Placebo subcutaneous injections every 4 weeks in participants with cholinergic urticaria
Intervention Type
Drug
Intervention Name(s)
Ligelizumab
Other Intervention Name(s)
QGE031
Intervention Description
Ligelizumab treated groups and arms
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo treated groups and arms
Primary Outcome Measure Information:
Title
Change From Baseline in Total Fric Score in Participants With Symptomatic Dermographism
Description
Total Fric score (a scale of 0-4 where 0= no linear hive ≥ 3mm in width, 1= one linear hive ≥ 3mm in width, 2= two linear hives ≥ 3mm in width, 3= three linear hives ≥ 3mm in width and 4 = four linear hives ≥ 3mm in width)
None of the participants completed Week 12 and hence at Week 12 was not analyzed
Time Frame
Baseline, Week 12
Title
Change From Baseline in Critical Temperature Threshold in Participants With Cold Urticaria
Description
The TempTest is used to induce itch and hives in participants with cold urticaria. Critical temperature threshold (CTT), as measured by the TempTest, determines the highest temperature sufficient for inducing symptoms.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Itch Numerical Rating Scale in Participants With Cholinergic Urticaria
Description
Itch numerical rating scale, a scale from 0 to 10. Negative change from baseline indicates improvement.
Patients were asked to rate itching severity based on the worst level of itching in the past 24 h using an 11-point scale from 0 ("no itch") to 10 ("worst possible itch")
Time Frame
Baseline, Week 12
Secondary Outcome Measure Information:
Title
Proportion of Participants With Symptomatic Dermographism With Total Fric Score = 0
Description
Total Fric score (a scale of 0-4 where 0= no linear hive ≥ 3mm in width, 1= one linear hive ≥ 3mm in width, 2= two linear hives ≥ 3mm in width, 3= three linear hives ≥ 3mm in width and 4 = four linear hives ≥ 3mm in width)
None of the participants completed Week 12
Time Frame
Week 12
Title
Change From Baseline in Itch Numerical Rating Scale in Participants With Symptomatic Dermographism
Description
Itch numerical rating scale, a scale from 0 to 10. Negative change from baseline indicates improvement.
Patients were asked to rate itching severity based on the worst level of itching in the past 24 h using an 11-point scale from 0 ("no itch") to 10 ("worst possible itch")
Time Frame
Baseline, Week 12
Title
Proportion of Participants With Cold Urticaria With Complete Response (no Itch or Hives) to the TempTest
Description
The TempTest® is used to induce itch and hives in participants with cold urticaria. Critical temperature threshold (CTT), as measured by the TempTest, determines the highest temperature sufficient for inducing symptoms.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Itch Numerical Rating Scale in Participants With Cold Urticaria
Description
Itch numerical rating scale, a scale from 0 to 10. Negative change from baseline indicates improvement.
Patients were asked to rate itching severity based on the worst level of itching in the past 24 h using an 11-point scale from 0 ("no itch") to 10 ("worst possible itch")
Time Frame
Baseline, Week 12
Title
Proportion of Participants With Cholinergic Urticaria With Itch Numerical Rating Scale =0
Description
Itch numerical rating scale, a scale from 0 to 10. Negative change from baseline indicates improvement.
Patients were asked to rate itching severity based on the worst level of itching in the past 24 h using an 11-point scale from 0 ("no itch") to 10 ("worst possible itch")
Time Frame
Week 12
Title
Proportion of Participants With Cholinergic Urticaria With Physician Global Assessment of Severity of Hives (PGA - Hive Score) =0
Description
Physician global assessment of severity of hives
PGA is an assessment of all lesions scored on a scale from 0-5 (with 0 = No hives and 5 = Very severe hives)
Time Frame
Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Confirmed CINDU diagnosis (as per guidelines) for symptomatic dermographism, cold urticaria or cholinergic urticaria for ≥ 4 months.
Diagnosis of CINDU (symptomatic dermographism, cold urticaria or cholinergic urticaria) inadequately controlled with H1-AH at local label approved doses at the time of randomization, as defined by all of the following:
Positive response (i.e development of symptoms) to triggers despite treatment with H1-AH
Positive response (i.e. development of symptoms) to provocation test on day of randomization
Participants must be able to physically perform the protocol defined provocation test specific to the participant's CINDU.
Cholinergic urticaria participants must show sweating in performing the pulse-controlled ergometry test on day of randomization. Participants with anhidrosis must not be included.
Willing and able to complete a daily symptom eDiary as per protocol requirement and adhere to the study visit schedules
Exclusion Criteria:
History of hypersensitivity to any of the study drugs or its components or to drugs of similar chemical classes or to the provocation test or items used in provocation tests
Participants who have concomitant CSU at screening
Participants who have a familial form of the target CINDU that is being considered for the participant's inclusion in this study
Participants having a more defined other form of inducible urticaria than the target CINDU that is being considered for the participant's inclusion in this study
Diseases, other than chronic inducible urticaria, with urticarial or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema (eg, due to C1 inhibitor deficiency).
Any other skin disease associated with chronic itching that might influence, in the investigator's opinion, the study evaluations and results (eg, atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.) or skin diseases associated with only wheals and no itch e.g asymptomatic dermographism
Prior exposure to ligelizumab, omalizumab and or other anti-IgE therapies
Facility Information:
Facility Name
Novartis Investigative Site
City
Evansville
State/Province
Indiana
ZIP/Postal Code
47713
Country
United States
Facility Name
Novartis Investigative Site
City
North Charleston
State/Province
South Carolina
ZIP/Postal Code
29420
Country
United States
Facility Name
Novartis Investigative Site
City
El Paso
State/Province
Texas
ZIP/Postal Code
79903
Country
United States
Facility Name
Novartis Investigative Site
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
Novartis Investigative Site
City
East Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Facility Name
Novartis Investigative Site
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Facility Name
Novartis Investigative Site
City
Athens
ZIP/Postal Code
12462
Country
Greece
Facility Name
Novartis Investigative Site
City
Debrecen
State/Province
Hajdu Bihar
ZIP/Postal Code
4026
Country
Hungary
Facility Name
Novartis Investigative Site
City
Pecs
ZIP/Postal Code
7632
Country
Hungary
Facility Name
Novartis Investigative Site
City
Szeged
ZIP/Postal Code
6720
Country
Hungary
Facility Name
Novartis Investigative Site
City
Izhevsk
ZIP/Postal Code
426061
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Rostov On Don
ZIP/Postal Code
344022
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Saint Petersburg
ZIP/Postal Code
194354
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Saint Petersburg
ZIP/Postal Code
198260
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
St Petersburg
ZIP/Postal Code
194156
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Stavropol
ZIP/Postal Code
355000
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Kezmarok
ZIP/Postal Code
060 01
Country
Slovakia
Facility Name
Novartis Investigative Site
City
Svidnik
ZIP/Postal Code
08901
Country
Slovakia
Facility Name
Novartis Investigative Site
City
Cordoba
State/Province
Andalucia
ZIP/Postal Code
14004
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08003
Country
Spain
Facility Name
Novartis Investigative Site
City
Valencia
State/Province
Comunidad Valenciana
ZIP/Postal Code
46026
Country
Spain
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Novartis Investigative Site
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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
Learn more about this trial
Study of Efficacy and Safety of Ligelizumab in Adolescents and Adults With Chronic Inducible Urticaria Who Remain Symptomatic Despite Treatment With H1- Antihistamines
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