Study of Efficacy and Safety of Ligelizumab in Adolescents and Adults With Chronic Inducible Urticaria Who Remain Symptomatic Despite Treatment With H1- Antihistamines (PEARL-PROVOKE)

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

Study Overview

• Status: Terminated
• Conditions: Chronic Inducible Urticaria
• Intervention / Treatment: Drug: Ligelizumab; Other: Placebo

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 Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Novartis Investigative Site
    • Parkville, Victoria, Australia, 3002
      • Novartis Investigative Site
• Greece
  • Athens, Greece, 12462
    • Novartis Investigative Site
• Hungary
  • Pecs, Hungary, 7632
    • Novartis Investigative Site
  • Szeged, Hungary, 6720
    • Novartis Investigative Site
  • Hajdu Bihar
    • Debrecen, Hajdu Bihar, Hungary, 4026
      • Novartis Investigative Site
• Russian Federation
  • Izhevsk, Russian Federation, 426061
    • Novartis Investigative Site
  • Rostov On Don, Russian Federation, 344022
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 194354
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 198260
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 194156
    • Novartis Investigative Site
  • Stavropol, Russian Federation, 355000
    • Novartis Investigative Site
• Slovakia
  • Kezmarok, Slovakia, 060 01
    • Novartis Investigative Site
  • Svidnik, Slovakia, 08901
    • Novartis Investigative Site
• Spain
  • Andalucia
    • Cordoba, Andalucia, Spain, 14004
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08003
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46026
      • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06100
    • Novartis Investigative Site
  • Istanbul, Turkey, 34093
    • Novartis Investigative Site
• United States
  • Indiana
    • Evansville, Indiana, United States, 47713
      • Novartis Investigative Site
  • South Carolina
    • North Charleston, South Carolina, United States, 29420
      • Novartis Investigative Site
  • Texas
    • El Paso, Texas, United States, 79903
      • Novartis Investigative Site
  • Utah
    • Murray, Utah, United States, 84107
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ligelizumab low dose, symptomatic dermographism group; Ligelizumab low dose subcutaneous injection every 4 weeks in participants with symptomatic dermographism	Drug: Ligelizumab; Ligelizumab treated groups and arms; Other Names: QGE031
Experimental: Ligelizumab high dose, symptomatic dermographism; Ligelizumab high dose subcutaneous injection every 4 weeks in participants with symptomatic dermographism	Drug: Ligelizumab; Ligelizumab treated groups and arms; Other Names: QGE031
Placebo Comparator: Placebo SC q4W, symptomatic dermographism; Placebo subcutaneous injection every 4 weeks in participants with symptomatic dermographism	Other: Placebo; Placebo treated groups and arms
Experimental: Ligelizumab low dose, cold urticaria; Ligelizumab low dose subcutaneous injection every 4 weeks in participants with cold urticaria	Drug: Ligelizumab; Ligelizumab treated groups and arms; Other Names: QGE031
Experimental: Ligelizumab high dose, cold urticaria; Ligelizumab high dose subcutaneous injections every 4 weeks in participants with cold urticaria	Drug: Ligelizumab; Ligelizumab treated groups and arms; Other Names: QGE031
Placebo Comparator: Placebo SC q4w, cold urticaria; Placebo subcutaneous injection every 4 weeks in participants with cold urticaria	Other: Placebo; Placebo treated groups and arms
Experimental: Ligelizumab high dose, cholinergic urticaria; Ligelizumab high dose subcutaneous injections every 4 weeks in participants with cholinergic urticaria	Drug: Ligelizumab; Ligelizumab treated groups and arms; Other Names: QGE031
Placebo Comparator: Placebo SC q4w, cholinergic urticaria; Placebo subcutaneous injections every 4 weeks in participants with cholinergic urticaria	Other: Placebo; Placebo treated groups and arms

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	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")	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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")	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.	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")	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")	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)	Week 12

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2021
• Primary Completion (Actual): August 9, 2022
• Study Completion (Actual): August 9, 2022

Study Registration Dates

• First Submitted: August 23, 2021
• First Submitted That Met QC Criteria: August 23, 2021
• First Posted (Actual): August 27, 2021

Study Record Updates

• Last Update Posted (Actual): September 15, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: itch; hives; urticaria; chronic inducible urticaria; cholinergic urticaria; cold urticaria; ligelizumab; anti-IgE; CINDU; symptomatic dermographism
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Disease Attributes; Skin Diseases, Vascular; Hypersensitivity; Chronic Disease; Chronic Urticaria; Urticaria; Chronic Inducible Urticaria
• Other Study ID Numbers: CQGE031E12301; 2020-003018-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No