Chronic Inducible Urticaria
Conditions
Keywords
ligelizumab, anti-IgE, CINDU, chronic inducible urticaria, symptomatic dermographism, cold urticaria, cholinergic urticaria, urticaria, itch, hives
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.
Interventions
DRUGLigelizumab
Ligelizumab treated groups and arms
OTHERPlacebo
Placebo treated groups and arms
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Fric Score in Participants With Symptomatic Dermographism | Baseline, Week 12 | 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 | Baseline, Week 12 | 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 | Baseline, Week 12 | 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
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Itch Numerical Rating Scale in Participants With Cold Urticaria | Baseline, Week 12 | 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 Symptomatic Dermographism With Total Fric Score = 0 | Week 12 | 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 |
| Proportion of Participants With Cholinergic Urticaria With Physician Global Assessment of Severity of Hives (PGA - Hive Score) =0 | Week 12 | 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) |
| Proportion of Participants With Cholinergic Urticaria With Itch Numerical Rating Scale =0 | Week 12 | 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) |
| Change From Baseline in Itch Numerical Rating Scale in Participants With Symptomatic Dermographism | Baseline, Week 12 | 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 | Baseline, Week 12 | 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. |
Countries
Australia, Greece, Hungary, Russia, Slovakia, Spain, Taiwan, Turkey (Türkiye), United States
Participant flow
Recruitment details
39 participants were randomized. None completed study.
Pre-assignment details
There were no pre-assignment details for this study.
Participants by arm
| Arm | Count |
|---|---|
| 72 mg Ligelizumab, Symptomatic Dermographism 72 mg ligelizumab subcutaneous injections every 4 weeks in participants with symptomatic dermographism | 5 |
| 120 mg Ligelizumab, Symptomatic Dermographism 120 mg ligelizumab subcutaneous injections every 4 weeks in participants with symptomatic dermographism | 6 |
| Placebo - 72 mg Ligelizumab, Symptomatic Dermographism Placebo every 4 weeks until week 12 followed by 72 mg ligelizumab subcutaneous injections in participants with symptomatic dermographism | 4 |
| Placebo - 120 mg Ligelizumab, Symptomatic Dermographism Placebo every 4 weeks until week 12 followed by 120 mg ligelizumab subcutaneous injections in participants with symptomatic dermographism | 2 |
| 72 mg Ligelizumab Cold Urticaria 72 mg ligelizumab subcutaneous injections every 4 weeks in participants with cold urticaria | 3 |
| 120 mg Ligelizumab, Cold Urticaria 120 mg ligelizumab subcutaneous injections every 4 weeks in participants with cold urticaria | 3 |
| Placebo - 72 mg Ligelizumab, Cold Urticaria Placebo every 4 weeks until week 12 followed by 72 mg ligelizumab subcutaneous injections in participants with cold urticaria | 1 |
| Placebo - 120 mg Ligelizumab, Cold Urticaria Placebo every 4 weeks until week 12 followed by 72 mg ligelizumab subcutaneous injections in participants with cold urticaria | 3 |
| 120 mg Ligelizumab, Cholinergic Urticaria 120 mg ligelizumab subcutaneous injection every 4 weeks in participants with cholinergic urticaria | 6 |
| Placebo - 120 mg Ligelizumab, Cholinergic Urticaria Placebo every 4 weeks until week 12 followed by 120 mg ligelizumab subcutaneous injections in participants with cholinergic urticaria | 6 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Follow-up | Withdrawal by Subject | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Treatment | Study terminated by sponsor | 5 | 6 | 4 | 2 | 3 | 3 | 1 | 3 | 6 | 6 |
Baseline characteristics
| Characteristic | 72 mg Ligelizumab, Symptomatic Dermographism | 120 mg Ligelizumab, Symptomatic Dermographism | Placebo - 72 mg Ligelizumab, Symptomatic Dermographism | Placebo - 120 mg Ligelizumab, Symptomatic Dermographism | 72 mg Ligelizumab Cold Urticaria | 120 mg Ligelizumab, Cold Urticaria | Placebo - 72 mg Ligelizumab, Cold Urticaria | Placebo - 120 mg Ligelizumab, Cold Urticaria | 120 mg Ligelizumab, Cholinergic Urticaria | Placebo - 120 mg Ligelizumab, Cholinergic Urticaria | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 5 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 5 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 2 Participants | 6 Participants | 6 Participants | 34 Participants |
| Age, Continuous | 30.4 years STANDARD_DEVIATION 9.81 | 28.3 years STANDARD_DEVIATION 12.74 | 40.8 years STANDARD_DEVIATION 18.86 | 36.5 years STANDARD_DEVIATION 12.02 | 35.3 years STANDARD_DEVIATION 12.5 | 31.7 years STANDARD_DEVIATION 16.17 | 60.0 years | 32.3 years STANDARD_DEVIATION 26.58 | 28.8 years STANDARD_DEVIATION 9.62 | 25.2 years STANDARD_DEVIATION 5.56 | 27.0 years STANDARD_DEVIATION 7.73 |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 6 Participants | 4 Participants | 2 Participants | 3 Participants | 3 Participants | 1 Participants | 3 Participants | 5 Participants | 5 Participants | 36 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 19 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 4 Participants | 6 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 15 | 0 / 5 | 0 / 11 | 0 / 39 |
| other Total, other adverse events | 3 / 8 | 6 / 15 | 3 / 5 | 1 / 11 | 13 / 39 |
| serious Total, serious adverse events | 0 / 8 | 0 / 15 | 0 / 5 | 0 / 11 | 0 / 39 |
Outcome results
Primary
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.
Time frame: Baseline, Week 12
Population: RAN consisted of all randomized participants, regardless of whether or not they received a dose of drug. Participants were analyzed according to the treatment they were assigned.~Due to the limited number of participants who completed the primary endpoint timepoint (Week 12), no inferential statistical analysis was done for primary and secondary endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 72 mg Ligelizumab, Symptomatic Dermographism | Change From Baseline in Critical Temperature Threshold in Participants With Cold Urticaria | -26 Temperature (degrees celcius) |
| 120 mg Ligelizumab, Symptomatic Dermographism | Change From Baseline in Critical Temperature Threshold in Participants With Cold Urticaria | -15 Temperature (degrees celcius) |
Primary
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)
Time frame: Baseline, Week 12
Population: RAN consisted of all randomized participants, regardless of whether or not they received a dose of drug. Participants were analyzed according to the treatment they were assigned.~Due to the limited number of participants who completed the primary endpoint timepoint (Week 12), no inferential statistical analysis was done for primary and secondary endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 72 mg Ligelizumab, Symptomatic Dermographism | Change From Baseline in Itch Numerical Rating Scale in Participants With Cholinergic Urticaria | -7 Scores on a scale |
Primary
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
Time frame: Baseline, Week 12
Population: The Randomized Analysis Set (RAN) consisted of all randomized participants, regardless of whether or not they received a dose of drug. Participants were analyzed according to the treatment they were assigned.~Due to the limited number of participants who completed the primary endpoint timepoint (Week 12), no inferential statistical analysis was done for primary and secondary endpoints.
Secondary
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)
Time frame: Baseline, Week 12
Population: RAN consisted of all randomized participants, regardless of whether or not they received a dose of drug. Participants were analyzed according to the treatment they were assigned.~Due to the limited number of participants who completed the primary endpoint timepoint (Week 12), no inferential statistical analysis was done for primary and secondary endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 72 mg Ligelizumab, Symptomatic Dermographism | Change From Baseline in Itch Numerical Rating Scale in Participants With Cold Urticaria | -9 Scores on a scale |
| 120 mg Ligelizumab, Symptomatic Dermographism | Change From Baseline in Itch Numerical Rating Scale in Participants With Cold Urticaria | 0 Scores on a scale |
Secondary
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)
Time frame: Baseline, Week 12
Population: RAN consisted of all randomized participants, regardless of whether or not they received a dose of drug. Participants were analyzed according to the treatment they were assigned.~No participants completed week 12.
Secondary
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)
Time frame: Week 12
Population: RAN consisted of all randomized participants, regardless of whether or not they received a dose of drug. Participants were analyzed according to the treatment they were assigned.~Due to the limited number of participants who completed the primary endpoint timepoint (Week 12), no inferential statistical analysis was done for primary and secondary endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 72 mg Ligelizumab, Symptomatic Dermographism | Proportion of Participants With Cholinergic Urticaria With Itch Numerical Rating Scale =0 | 0 Proportion of participants |
| 120 mg Ligelizumab, Symptomatic Dermographism | Proportion of Participants With Cholinergic Urticaria With Itch Numerical Rating Scale =0 | 0 Proportion of participants |
Secondary
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)
Time frame: Week 12
Population: RAN consisted of all randomized participants, regardless of whether or not they received a dose of drug. Participants were analyzed according to the treatment they were assigned.~Due to the limited number of participants who completed the primary endpoint timepoint (Week 12), no inferential statistical analysis was done for primary and secondary endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 72 mg Ligelizumab, Symptomatic Dermographism | Proportion of Participants With Cholinergic Urticaria With Physician Global Assessment of Severity of Hives (PGA - Hive Score) =0 | 0 Proportion of participants |
Secondary
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.
Time frame: Baseline, Week 12
Population: RAN consisted of all randomized participants, regardless of whether or not they received a dose of drug. Participants were analyzed according to the treatment they were assigned.~Due to the limited number of participants who completed the primary endpoint timepoint (Week 12), no inferential statistical analysis was done for primary and secondary endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 72 mg Ligelizumab, Symptomatic Dermographism | Proportion of Participants With Cold Urticaria With Complete Response (no Itch or Hives) to the TempTest | 1 Proportion of participants |
| 120 mg Ligelizumab, Symptomatic Dermographism | Proportion of Participants With Cold Urticaria With Complete Response (no Itch or Hives) to the TempTest | 0 Proportion of participants |
Secondary
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
Time frame: Week 12
Population: RAN consisted of all randomized participants, regardless of whether or not they received a dose of drug. Participants were analyzed according to the treatment they were assigned.~Due to the limited number of participants who completed the primary endpoint timepoint (Week 12), no inferential statistical analysis was done for primary and secondary endpoints.