Study of Mechanism of Action of Ligelizumab (QGE031) in Patients With Chronic Urticaria

Brief Title

Study of Mechanism of Action of Ligelizumab (QGE031) in Patients With Chronic Urticaria

Official Title

A Two-part Exploratory Study Combining a Pilot Study in Healthy Subjects and Chronic Spontaneous Urticaria Patients (Part 1) and a Randomized, Subject, Investigator and Sponsor-blinded, Placebo Controlled, Study (Part 2) to Assess the MechAniSm of acTion of ligElizumab (QGE031) in Patients With Chronic uRticaria (MASTER)

Brief Summary

      The purpose of the study is to investigate the mechanism of action for ligelizumab (QGE031)
      treatment in patients with chronic urticaria.

      The study has two parts. The study population will consist of approximately 68 male and
      female healthy volunteers and patients. In Part 1, approximately 20 healthy volunteers and
      patients with chornic urticaria will be enrolled. In Part 2 approximately 48 patients with
      chronic urticaria (spontaneous chronic urticaria, cholinergic urticaria or cold urticaria).
      Part 1 consists of a screening period up 2 weeks and a visit with skin tests; there is no
      treatment taken in Part 1. Part 2 is randomized, subject, investigator and sponsor blinded.
      It consists of a screening period up to 4 weeks, a 16 week treatment period and a 12-week
      follow-up period after last treatment. A follow-up call at Week 32 will be performed via
      telephone.
    

Detailed Description

      There are 58 patients out of 68 participants (10 are Healthy Volunteers)
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Part 1: Wheal and erythema size after skin prick test with several different ciprofloxacin and icatibant concentrations.

Secondary Outcome

 Part 2: Change in wheal volume and duration, erythema size and duration, itch intensity and duration

Condition

Chronic Spontaneous Urticaria

Intervention

Ligelizumab

Study Arms / Comparison Groups

 Ligelizumab
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

68

Start Date

August 5, 2020

Completion Date

July 12, 2022

Primary Completion Date

July 12, 2022

Eligibility Criteria

        Inclusion Criteria:

        Healthy volunteers

        • Healthy male and female subjects in good health as determined by past medical history,
        physical examination, vital signs, electrocardiogram, and laboratory tests at screening.

        CSU and CINDU patients (cold and cholinergic urticaria) CSU patients

          -  Diagnosis of CSU (acc. to criteria defined in Zuberbier et al 2018) not adequately
             controlled with H1-AH at approved doses alone at the time of randomization, as defined
             by all of the following:

          -  UAS7 score (range 0-42) ≥ 16 and HSS7 (range 0-21) ≥ 8 during 7 days prior to
             randomization

          -  CSU for ≥ 6 months CINDU patients (cold and cholinergic urticaria)

          -  For patients with cold urticaria: Cold urticaria symptoms persisting for at least 6
             months prior to study enrollment and a positive cold urticaria provocation test
             defined as wheal response to TempTest 4.0® at Day 1.

          -  For patients with cholinergic urticaria: Cholinergic urticaria symptoms for at least 6
             months prior to enrollment and a positive response in the challenge test defined as a
             wheal response in the pulse controlled ergometry provocation test (30 minutes bicycle
             challenge).

        Exclusion Criteria:

        Healthy volunteers

          -  History of allergies or allergy to the challenge substances including ciprofloxacin,
             icatibant, other quinolones or excipients of the substances being used in the study.

          -  Recent (within the last three years) and/or recurrent history of autonomic dysfunction
             (e.g. recurrent episodes of fainting, palpitations, etc.).

          -  Donation or loss of 450 mL or more blood within eight weeks prior to initial dosing,
             or longer if required by local regulations.

        CSU and CINDU patients (cold and cholinergic urticaria)

          -  History of allergies or allergy to the challenge substances including ciprofloxacin,
             icatibant, other quinolones or excipients of the substances being used in this study.

          -  Contraindications to or hypersensitivity to antihistamines (such as fexofenadine,
             loratadine, cetirizine, rupatadine, bilastine) or epinephrine or any of the
             ingredients.

          -  History or presence of renal disease and/or estimated glomerular filtration (eGFR)
             rate of < 35 mL/min as calculated by the CKD-EPI formula at Screening.

          -  For subjects who enter Part 2: Patients with a history of or a risk of parasite
             infections (recent stay in tropical/subtropical areas with low hygiene standards). To
             allow enrollment of a patient at risk perform stool examinations for ova or parasites
             and demonstrate absence of infection first.

          -  Diseases with possible signs and symptoms of urticaria or angioedema such as
             urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria
             pigmentosa), and hereditary or acquired angioedema (e.g. due to C1 inhibitor
             deficiency).

        CSU patients

          -  Clearly defined underlying etiology for chronic urticaria symptoms other than CSU.
             This includes the following:

          -  CSU patients should not have inducible urticaria forms impacting their daily symptoms
             in a relevant way, such as but not limited to urticaria factitia, cold-, heat-,
             solar-, pressure-, delayed pressure, aquagenic-, cholinergic-, or contact-urticaria.

        CINDU patients (cold and cholinergic urticaria)

          -  Clearly defined underlying etiology for chronic urticaria symptoms other than CINDU.
             This includes the following:

          -  CINDU patients should not have spontaneous urticaria impacting their symptoms in a
             relevant way.

        Other protocol-defined inclusion/exclusion criteria may apply .
      

Gender

All

Ages

18 Years - 79 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Novartis Pharmaceuticals, +41613241111, [email protected]

Location Countries

Germany

Location Countries

Germany

Administrative Informations


NCT ID

NCT04513548

Organization ID

CQGE031C2203

Secondary IDs

2019-001048-24

Responsible Party

Sponsor

Study Sponsor

Novartis Pharmaceuticals


Study Sponsor

Novartis Pharmaceuticals, Study Director, Novartis Pharmaceuticals


Verification Date

September 2020