Chronic Inducible UrticariaPhase 3PEARL-PROVOKENCT05024058
Study of Efficacy and Safety of Ligelizumab in Adolescents and Adults With Chronic Inducible Urticaria Who Remain Symptomatic Despite Treatment With H1- Antihistamines
A Phase 3 study testing Ligelizumab in people with Chronic Inducible Urticaria, run by Novartis Pharmaceuticals at 24 sites in 9 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Chronic Inducible Urticaria
- What is being tested?
- Ligelizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 24 sitesin 9 countries
- Study dates
- 16 Nov 2021to 9 Aug 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
24 sites in 9 countries.
24 sites in 9 countries
Russia6 sites
Novartis Investigative Site
Izhevsk, 426061
Novartis Investigative Site
Rostov-on-Don, 344022
Novartis Investigative Site
Saint Petersburg, 194156
Novartis Investigative Site
Saint Petersburg, 194354
Novartis Investigative Site
Saint Petersburg, 198260
Novartis Investigative Site
Stavropol, 355000
United States4 sites
Novartis Investigative Site
El Paso, Texas, 79903
Novartis Investigative Site
Evansville, Indiana, 47713
Novartis Investigative Site
Murray, Utah, 84107
Novartis Investigative Site
North Charleston, South Carolina, 29420
Hungary3 sites
Novartis Investigative Site
Debrecen, Hajdú-Bihar, 4026
Novartis Investigative Site
Pécs, 7632
Novartis Investigative Site
Szeged, 6720
Spain3 sites
Novartis Investigative Site
Barcelona, Catalonia, 08003
Novartis Investigative Site
Córdoba, Andalusia, 14004
Novartis Investigative Site
Valencia, Valencia, 46026
Australia2 sites
Novartis Investigative Site
East Melbourne, Victoria, 3002
Novartis Investigative Site
Parkville, Victoria, 3002
Slovakia2 sites
Novartis Investigative Site
Kežmarok, 060 01
Novartis Investigative Site
Svidník, 08901
Turkey (Türkiye)2 sites
Novartis Investigative Site
Ankara, 06100
Novartis Investigative Site
Istanbul, 34093
About this study
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
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
Read the 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.
- Conditions
- Chronic Inducible Urticaria
- Being tested
- Ligelizumab, Placebo
- Keywords
- ligelizumab, anti-IgE, CINDU, chronic inducible urticaria, symptomatic dermographism, cold urticaria, cholinergic urticaria, urticaria, itch, hives
- Medical subject headings
- Chronic Inducible Urticaria, Familial dermographism, Cold Urticaria, Urticaria, Pruritus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LigelizumabDrug
Also called QGE031
Ligelizumab treated groups and arms
PlaceboOther
Placebo treated groups and arms
| Study group | Role | What they receive |
|---|---|---|
| Ligelizumab low dose, symptomatic dermographism group | Experimental | Ligelizumab low dose subcutaneous injection every 4 weeks in participants with symptomatic dermographism Receives: Drug: Ligelizumab |
| Ligelizumab high dose, symptomatic dermographism | Experimental | Ligelizumab high dose subcutaneous injection every 4 weeks in participants with symptomatic dermographism Receives: Drug: Ligelizumab |
| Placebo SC q4W, symptomatic dermographism | Placebo comparator | Placebo subcutaneous injection every 4 weeks in participants with symptomatic dermographism Receives: Other: Placebo |
| Ligelizumab low dose, cold urticaria | Experimental | Ligelizumab low dose subcutaneous injection every 4 weeks in participants with cold urticaria Receives: Drug: Ligelizumab |
| Ligelizumab high dose, cold urticaria | Experimental | Ligelizumab high dose subcutaneous injections every 4 weeks in participants with cold urticaria Receives: Drug: Ligelizumab |
| Placebo SC q4w, cold urticaria | Placebo comparator | Placebo subcutaneous injection every 4 weeks in participants with cold urticaria Receives: Other: Placebo |
| Ligelizumab high dose, cholinergic urticaria | Experimental | Ligelizumab high dose subcutaneous injections every 4 weeks in participants with cholinergic urticaria Receives: Drug: Ligelizumab |
| Placebo SC q4w, cholinergic urticaria | Placebo comparator | Placebo subcutaneous injections every 4 weeks in participants with cholinergic urticaria Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline, Week 12
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.
Measured: Baseline, Week 12
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")
Measured: Baseline, Week 12
Secondary outcomes (6)
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
Measured: 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")
Measured: Baseline, Week 12
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.
Measured: Baseline, Week 12
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")
Measured: Baseline, Week 12
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")
Measured: Week 12
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)
Measured: Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2021
- Study start16 Nov 2021
- Primary completion9 Aug 2022
- Study completion9 Aug 2022
Why it 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Inducible UrticariaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05024058
- Sponsor's protocol ID
- CQGE031E12301
- Other IDs
- 2020-003018-11
- Acronym
- PEARL-PROVOKE
- Status last verified
- Jun 2024
- First submitted
- 23 Aug 2021
- Last updated
- 18 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05024058
- Acronym / sponsor ID
- PEARL-PROVOKE / CQGE031E12301
- Conditions
- Chronic Inducible Urticaria
- Keywords
- ligelizumab, anti-IgE, CINDU, chronic inducible urticaria, symptomatic dermographism, cold urticaria, cholinergic urticaria, urticaria
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason 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.
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 16 Nov 2021 (actual)
- Primary completion
- 9 Aug 2022 (actual)
- Study completion
- 9 Aug 2022 (actual)
- First posted
- 27 Aug 2021 (actual)
- Results
- Posted 15 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Ligelizumab low dose, symptomatic dermographism group | Experimental | Drug: LigelizumabLigelizumab low dose subcutaneous injection every 4 weeks in participants with symptomatic dermographism |
| Ligelizumab high dose, symptomatic dermographism | Experimental | Drug: LigelizumabLigelizumab high dose subcutaneous injection every 4 weeks in participants with symptomatic dermographism |
| Placebo SC q4W, symptomatic dermographism | Placebo comparator | Other: PlaceboPlacebo subcutaneous injection every 4 weeks in participants with symptomatic dermographism |
| Ligelizumab low dose, cold urticaria | Experimental | Drug: LigelizumabLigelizumab low dose subcutaneous injection every 4 weeks in participants with cold urticaria |
| Ligelizumab high dose, cold urticaria | Experimental | Drug: LigelizumabLigelizumab high dose subcutaneous injections every 4 weeks in participants with cold urticaria |
| Placebo SC q4w, cold urticaria | Placebo comparator | Other: PlaceboPlacebo subcutaneous injection every 4 weeks in participants with cold urticaria |
| Ligelizumab high dose, cholinergic urticaria | Experimental | Drug: LigelizumabLigelizumab high dose subcutaneous injections every 4 weeks in participants with cholinergic urticaria |
| Placebo SC q4w, cholinergic urticaria | Placebo comparator | Other: PlaceboPlacebo subcutaneous injections every 4 weeks in participants with cholinergic urticaria |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Confirmed CINDU diagnosis (as per guidelines) for symptomatic dermographism, cold urticaria or cholinergic urticaria for ≥ 4 months.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LigelizumabAlso: QGE031Ligelizumab treated groups and arms | Drug | Ligelizumab high dose, cholinergic urticaria, Ligelizumab high dose, cold urticaria, Ligelizumab high dose, symptomatic dermographism, Ligelizumab low dose, cold urticaria, Ligelizumab low dose, symptomatic dermographism group |
| PlaceboPlacebo treated groups and arms | Other | Placebo SC q4W, symptomatic dermographism, Placebo SC q4w, cholinergic urticaria, Placebo SC q4w, cold urticaria |
Primary outcome
Change From Baseline in Total Fric Score in Participants With Symptomatic Dermographism
Time frame: 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
Time frame: 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
Time frame: 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")
6 secondary outcomes
Proportion of Participants With Symptomatic Dermographism With Total Fric Score = 0
Time frame: Week 12
Change From Baseline in Itch Numerical Rating Scale in Participants With Symptomatic Dermographism
Time frame: Baseline, Week 12
Proportion of Participants With Cold Urticaria With Complete Response (no Itch or Hives) to the TempTest
Time frame: Baseline, Week 12
Change From Baseline in Itch Numerical Rating Scale in Participants With Cold Urticaria
Time frame: Baseline, Week 12
Proportion of Participants With Cholinergic Urticaria With Itch Numerical Rating Scale =0
Time frame: Week 12
Proportion of Participants With Cholinergic Urticaria With Physician Global Assessment of Severity of Hives (PGA - Hive Score) =0
Time frame: Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Patient Lay Trial SummaryLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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
Related trials for Chronic Inducible Urticaria
RecruitingPhase 3
A Study to Investigate Efficacy, Safety and Tolerability of Barzolvolimab Versus Placebo in Adults With Cold Induced Urticaria and Symptomatic Dermographism Inadequately Controlled by H1-antihistamines (EMBARQ - ColdU and SD)
Chronic Inducible Urticaria, Cold Urticaria
RecruitingPhase 1
A Phase 1 Study of GTX-B001 in Healthy Subjects and Patients With Chronic Inducible Urticaria
Healthy Subjects, Cold Urticaria
Active, not recruitingPhase 3
A Study to Investigate Efficacy, Safety, and Tolerability of Remibrutinib Compared With Placebo in Adults With CINDU Inadequately Controlled by H1-antihistamines
Chronic Inducible Urticaria
Enrolling by invitationPhase 2
Apremilast Added to Antihistamines in Chronic Urticaria
Chronic Urticaria, Chronic Spontaneous Urticaria
RecruitingPhase 2
Study of Remibrutinib (LOU064) Efficacy and Safety and Exploration of Its Mechanism of Action in Participants With Chronic Urticaria
Chronic Urticaria (CU): Chronic Inducible Urticaria (CINDU) and Chronic Spontaneous Urticaria (CSU)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
24 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ligelizumab in people with Chronic Inducible Urticaria, run by Novartis Pharmaceuticals at 24 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in Russia, United States, Hungary, Spain, Australia and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Total Fric Score in Participants With Symptomatic Dermographism (time frame: Baseline, Week 12). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2024.