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)

Novartis

Status and phase: Terminated; Phase 3

Conditions: Chronic Inducible Urticaria

Treatments: Drug: Ligelizumab; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05024058

CQGE031E12301

2020-003018-11 (EudraCT Number)

Details and patient eligibility

About

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

Full 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.

Enrollment: 39 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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39 participants in 8 patient groups, including a placebo group

Ligelizumab low dose, symptomatic dermographism group

Experimental group

Description:

Ligelizumab low dose subcutaneous injection every 4 weeks in participants with symptomatic dermographism

Treatment:

Drug: Ligelizumab

Ligelizumab high dose, symptomatic dermographism

Experimental group

Description:

Ligelizumab high dose subcutaneous injection every 4 weeks in participants with symptomatic dermographism

Treatment:

Drug: Ligelizumab

Placebo SC q4W, symptomatic dermographism

Placebo Comparator group

Description:

Placebo subcutaneous injection every 4 weeks in participants with symptomatic dermographism

Treatment:

Other: Placebo

Ligelizumab low dose, cold urticaria

Experimental group

Description:

Ligelizumab low dose subcutaneous injection every 4 weeks in participants with cold urticaria

Treatment:

Drug: Ligelizumab

Ligelizumab high dose, cold urticaria

Experimental group

Description:

Ligelizumab high dose subcutaneous injections every 4 weeks in participants with cold urticaria

Treatment:

Drug: Ligelizumab

Placebo SC q4w, cold urticaria

Placebo Comparator group

Description:

Placebo subcutaneous injection every 4 weeks in participants with cold urticaria

Treatment:

Other: Placebo

Ligelizumab high dose, cholinergic urticaria

Experimental group

Description:

Ligelizumab high dose subcutaneous injections every 4 weeks in participants with cholinergic urticaria

Treatment:

Drug: Ligelizumab

Placebo SC q4w, cholinergic urticaria

Placebo Comparator group

Description:

Placebo subcutaneous injections every 4 weeks in participants with cholinergic urticaria

Treatment:

Other: Placebo