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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04513548
Recruitment Status : Active, not recruiting
First Posted : August 14, 2020
Last Update Posted : June 30, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.


Condition or disease Intervention/treatment Phase
Chronic Spontaneous Urticaria Cholinergic Urticaria Cold Urticaria Drug: Ligelizumab Drug: Placebo Phase 1

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 68 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: Part 1 is not masked Part 2 is masked
Primary Purpose: Basic Science
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)
Actual Study Start Date : August 5, 2020
Estimated Primary Completion Date : March 13, 2023
Estimated Study Completion Date : March 14, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hives

Arm Intervention/treatment
Experimental: Ligelizumab Drug: Ligelizumab
One injection every four weeks

Placebo Comparator: Placebo Drug: Placebo
One injection every four weeks




Primary Outcome Measures :
  1. Part 1: Wheal and erythema size after skin prick test with several different ciprofloxacin and icatibant concentrations. [ Time Frame: At Day 1 ]
    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.

  2. Part 2: Change in wheal size after challenge procedure from Day 1 (pre-dose) to week 16. [ Time Frame: Day 1 and Week 16 ]
    Size of wheal in mm2 after skin prick test and autologous serum skin test will be measured.


Secondary Outcome Measures :
  1. Part 2: Urticaria Control Test [ Time Frame: Day 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 ]
    The Urticaria Control Test (UCT) is a questionnaire that assesses the extent of the disease control over the previous 4 weeks. It consists of 4 questions, each rated from 0 to 4 points. Subsequently, the scores for all 4 questions are summed up. The minimum and maximum UCT scores are 0 and 16, with 12 points or higher indicating controlled disease, and 16 points indicating complete disease control.

  2. Part 2: Weekly Urticaria Activity Score [ Time Frame: Throughout the study (to 28 weeks) ]
    Chronic Spontaneous Urticaria (CSU) patients: The Urticaria Activity Score (UAS) is evaluated in the screening period and throughout the study. It records each morning and evening on a daily basis symptoms of itch and hives into a patient diary. The UAS is a composite score with numeric severity intensity ratings on a scale of 0 - 3 for the number of wheals (hives) and the itch intensity. The UAS7 is the sum of the daily UAS scores over 7 days. UAS7 values range from 0 to 42, with higher values indicate higher disease activity.

  3. Part 2: Cholinergic Urticaria Activity score [ Time Frame: Day 1 to Week 28 ]
    Cholinergic urticaria patients: Cholinergic Urticaria Activity score (CholUAS) is a questionnaire that records each evening on a daily basis symptoms of itch and hives and the general assessment of disease severity into a patient diary. The CholUAS is a composite score with numeric ratings on a scale of 0 - 3 for the intensity of wheals (hives), the itch intensity, and the overall assessment of the disease severity. The total score is a sum of scores multiplied with the score for the trigger. The CholUAS7 is the sum of the daily CholUAS scores over 7 days. Higher values indicate a higher disease activity.

  4. Part 2: Chronic Urticaria Quality of Life questionnaire [ Time Frame: Day 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 ]
    CSU patients: The Chronic Urticaria Quality of Life questionnaire (CU-Q2oL) is a questionnaire that measures the relative burden of chronic urticaria on subjective well-being. It consists of 23 questions in 3 domains (symptoms, general impairment, difficulties and problems due to urticaria). with a total score of 0 to 100 %. Higher scores indicate higher impairment in quality of life.

  5. Part 2: Angioedema control test [ Time Frame: Day 1, Week 16, Week 28 ]
    CSU patients with angioedema: Angioedema Control Test (AECT) is a questionnaire that assesses the extent of the symptom control (angioedema). It consists of 4 questions, each rated from 0 to 4 points. Subsequently, the scores for all 4 questions are summed up. The minimum and maximum AECT scores are 0 and 16, with 10 points or higher indicating controlled disease, and 16 points indicating complete disease control.

  6. Part 2: Cholinergic Urticaria Quality of Life questionnaire [ Time Frame: Day 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 ]
    Cholinergic patients: The Cholinergic Urticaria Quality of Life questionnaire (Chol-Q2oL) is a questionnaire that measures the relative burden of cholinergic urticaria on subjective well-being. The questionnaire consists of 28 items, each item being scored between 0 and 4. Higher scores indicate higher impairment in quality of life.

  7. Part 2: Provocation test for cholinergic patients [ Time Frame: Day 1, Week 4, Week 16, Week 28 ]
    Cholinergic patients: Time from onset of sweating and urticaria symptoms after an exercise on a stationary bicycle.

  8. Part 2: Temperature trigger test for cold urticaria patients [ Time Frame: Day 1, Week 4, Week 16, Week 28 ]
    Cold urticaria patients: The temperature that will provoke the formation of wheals will be assessed.

  9. Part 2: Safety and tolerability [ Time Frame: Throughout the study (to 28 weeks) ]
    Number of patients with adverse events



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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 .


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04513548


Locations
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Germany
Novartis Investigative Site
Berlin, Germany, 13353
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04513548    
Other Study ID Numbers: CQGE031C2203
2019-001048-24 ( EudraCT Number )
First Posted: August 14, 2020    Key Record Dates
Last Update Posted: June 30, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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


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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
chronic spontaneous urticaria
chronic inducible urticaria
cholinergic urticaria
cold urticaria
ligelizumab (QGE031)
Additional relevant MeSH terms:
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Urticaria
Chronic Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases