Clinical trial NCT04513548: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Chronic Spontaneous Urticaria
Cholinergic Urticaria
Cold Urticaria
Keywords: chronic spontaneous urticaria
chronic inducible urticaria
cholinergic urticaria
cold urticaria
ligelizumab (QGE031)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-08-14
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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)

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)

• 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

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 (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.

Other protocol-defined inclusion/exclusion criteria may apply .

Primary outcomes:
measure: Part 1: Wheal and erythema size after skin prick test with several different ciprofloxacin and icatibant concentrations.
timeFrame: At Day 1
measure: Part 2: Change in wheal size after challenge procedure from Day 1 (pre-dose) to week 16.
timeFrame: Day 1 and Week 16
Secondary outcomes:
measure: Part 2: Urticaria Control Test
timeFrame: Day 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28
measure: Part 2: Weekly Urticaria Activity Score
timeFrame: Throughout the study (to 28 weeks)
measure: Part 2: Cholinergic Urticaria Activity score
timeFrame: Day 1 to Week 28
measure: Part 2: Chronic Urticaria Quality of Life questionnaire
timeFrame: Day 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28
measure: Part 2: Angioedema control test
timeFrame: Day 1, Week 16, Week 28
measure: Part 2: Cholinergic Urticaria Quality of Life questionnaire
timeFrame: Day 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28
measure: Part 2: Provocation test for cholinergic patients
timeFrame: Day 1, Week 4, Week 16, Week 28
measure: Part 2: Temperature trigger test for cold urticaria patients
timeFrame: Day 1, Week 4, Week 16, Week 28
measure: Part 2: Number of patients with adverse events
timeFrame: Throughout the study (to 28 weeks)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: