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

NCT04513548 | Terminated Phase 1

• 2 other identifiers: CQGE031C22032019-001048-24
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Spontaneous Urticaria; Cholinergic Urticaria; Cold Urticaria

Keywords

chronic spontaneous urticaria; chronic inducible urticaria; cholinergic urticaria; cold urticaria; ligelizumab (QGE031)

Outcome Measures

Primary Outcomes (2)

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

  Size of the wheal and erythema in mm will be measured after the skin prick and intradermal tests are performed. Different dilution steps will be applied (to differentiate Chronic Spontaneous Urticaria patients and healthy controls) for ciprofloxacin and icatibant to determine the conditions to be used in Part 2.

  At Day 1

• Part 2: Change in wheal size after challenge procedure from Day 1 (pre-dose) to week 16.

  Size of wheal in mm2 after skin prick test and autologous serum skin test will be measured.

  Day 1 and Week 16

Secondary Outcomes (9)

• Part 2: Urticaria Control Test

  Day 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28

• Part 2: Weekly Urticaria Activity Score

  Throughout the study (to 28 weeks)

• Part 2: Cholinergic Urticaria Activity score

  Day 1 to Week 28

• Part 2: Chronic Urticaria Quality of Life questionnaire

  Day 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28

• Part 2: Angioedema control test

  Day 1, Week 16, Week 28

Study Arms (2)

Ligelizumab

EXPERIMENTAL

test drug

Drug: Ligelizumab

Placebo

PLACEBO COMPARATOR

placebo

Drug: Placebo

Interventions

Ligelizumab DRUG

One injection every four weeks

Ligelizumab

Placebo DRUG

One injection every four weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Part 2: Positive response to challenge test with ciprofloxacin 250 mg/ml or 125 mg/ml, defined as a wheal formation with longest diameter of at least 3 mm and middle perpendicular diameter of at least 2 mm at Day 1.
• CSU patients
• Diagnosis of CSU, 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) at Day 1

You may not qualify if:

• 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 (Part 1 only), 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Berlin, 13353, Germany

Location

Related Links

• Results for CQGE031C2203 from the Novartis Clinical Trials Website
• Patient Lay Trial Summary

MeSH Terms

Conditions

Chronic Urticaria; Cold Urticaria; Chronic Inducible Urticaria

Interventions

ligelizumab

Condition Hierarchy (Ancestors)

Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Part 1 is not masked Part 2 is masked
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2020
• First Posted: August 14, 2020
• Study Start: August 5, 2020
• Primary Completion: July 19, 2022
• Study Completion: July 19, 2022
• Last Updated: June 18, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)