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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03580356




Registration number
NCT03580356
Ethics application status
Date submitted
26/06/2018
Date registered
9/07/2018
Date last updated
8/07/2020

Titles & IDs
Public title
A Phase III Study of Efficacy and Safety of Ligelizumab in the Treatment of CSU in Adolescents and Adults Inadequately Controlled With H1-antihistamines.
Scientific title
A Multi-center, Randomized, Double-blind, Active and Placebo-controlled Study to Investigate the Efficacy and Safety of Ligelizumab (QGE031) in the Treatment of Chronic Spontaneous Urticaria (CSU) in Adolescents and Adults Inadequately Controlled With H1-antihistamines
Secondary ID [1] 0 0
CQGE031C2303
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Spontaneous Urticaria 0 0
Condition category
Condition code
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions
Inflammatory and Immune System 0 0 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Ligelizumab
Other interventions - Omalizumab
Other interventions - Placebo

Experimental: Ligelizumab Dose A - Ligelizumab Dose A q4w

Experimental: Ligelizumab Dose B - Ligelizumab Dose B q4w

Active Comparator: Omalizumab 300 mg - Omalizumab 300 mg q4w

Placebo Comparator: Placebo - Placebo q4w from randomization to week 20. Ligelizumab Dose B from week 24 to week 48.


Other interventions: Ligelizumab
Liquid in vial

Other interventions: Omalizumab
Lyophilized powder for solution in vial

Other interventions: Placebo
Liquid in vial

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Absolute change from baseline in UAS7 at Week 12 - The Urticaria Activity Score (UAS) is the sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS).
The HSS has a scale of 0 (none) to 3 (intense/severe). A weekly score (HSS7) is derived by adding up the average daily scores of the preceding 7 days.
The ISS also has a scale of 0 (none) to 3 (severe/difficult to tolerate). A weekly score (ISS7) is derived by adding up the average daily scores of the preceding 7 days.
The UAS7 is the sum of the HSS7 score and the ISS7 score, and has a possible range in score of 0-42.
Complete hives response is defined as HSS7 (average daily HSS over the preceding 7 days) = 0.
Complete itch response is defined as ISS7 (average daily ISS over the preceding 7 days) = 0.
Complete UAS7 response is defined as UAS7=0.
Timepoint [1] 0 0
Week 12
Secondary outcome [1] 0 0
Complete absence of hives and itch at Week 12 - Assessed as percentage of subjects achieving UAS7 = 0
Timepoint [1] 0 0
Week 12
Secondary outcome [2] 0 0
Improvement of severity of itch - Assessed as absolute change from baseline in ISS7 score at Week 12
Timepoint [2] 0 0
Week 12
Secondary outcome [3] 0 0
No impact on subject's quality of life at Week 12 - Assessed as percentage of subjects achieving DLQI = 0-1
Timepoint [3] 0 0
Week 12
Secondary outcome [4] 0 0
Cumulative number of weeks that subjects achieve AAS7 = 0 responses between baseline and Week 12 - To assess the cumulative period of time that treated subjects are angioedema occurrence-free
Timepoint [4] 0 0
Weekly to Week 12
Secondary outcome [5] 0 0
Occurrence of treatment emergent adverse events and serious adverse events during the study - Treatment emergent adverse events and serious adverse events are those which occur at any time only after treatment has started
Timepoint [5] 0 0
52 weeks

Eligibility
Key inclusion criteria
Key

- Signed informed consent must be obtained prior to participation in the study. The
subject's', parent'ssubject's, parent's or legal guardian's signed written informed
consent and child's assent, if appropriate, must be obtained before any assessment is
performed. Of note, if the subject reaches age of consent (age as per local law)
during the study, they will also need to sign the corresponding study Informed Consent
Form (ICF) at the next study visit.

- Male and female subjects = 12 years of age at the time of screening.

- CSU diagnosis for = 6 months.

- Diagnosis of CSU refractory to H1-AH at approved doses at the time of randomization,
as defined by all of the following:

- The presence of itch and hives for = 6 consecutive weeks at any time prior to Visit 1
(Day - 28 to Day -14) despite current use of non-sedating H1-AH

- UAS7 score (range 0-42) = 16 and HSS7 (range 0-21) = 8 during the 7 days prior to
randomization (Visit 110, Day 1)

- Subjects must be on H1-AH at only approved doses for treatment of CSU starting at
Visit 1 (Day -28 to Day -14)

- Willing and able to complete a daily symptom eDiary for the duration of the study and
adhere to the study visit schedules.

Key
Minimum age
12 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of hypersensitivity to any of the study drugs or their excipients or to drugs
of similar chemical classes (i.e. to murine, chimeric or human antibodies).

- Subjects having a clearly defined cause of their chronic urticaria, other than CSU.
This includes, but is not limited to, the following: symptomatic dermographism
(urticaria factitia), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-,
cholinergic- or contact-urticaria.

- Diseases, other than chronic 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).

- Subjects with evidence of helminthic parasitic infection as evidenced by stools being
positive for a pathogenic organism according to local guidelines. All subjects will be
screened at Visit 1. If stool testing is positive for pathogenic organism, the subject
will not be randomized and will not be allowed to rescreen.

- Any other skin disease associated with chronic itching that might influence in the
investigators opinion the study evaluations and results (e.g. atopic dermatitis,
bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.).

- Prior exposure to ligelizumab or omalizumab.

- Any H2 antihistamine, LTRA (montelukast or zafirlukast) or H1 antihistamines use at
greater than approved doses after Visit 1.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Darlinghurst
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Novartis Investigative Site - Adelaide
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Novartis Investigative Site - East Melbourne
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Novartis Investigative Site - Parkville
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2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3002 - East Melbourne
Recruitment postcode(s) [4] 0 0
3002 - Parkville
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to establish efficacy and safety of ligelizumab in adolescent
and adult subjects with CSU who remain symptomatic despite standard of care treatment by
demonstrating better efficacy over omalizumab.

The study population will consist of approximately 1050 male and female subjects aged = 12
years who have been diagnosed with CSU and who remain symptomatic despite the use of
H1-antihistamines. Of these, approximately 1000 adults and 50 adolescents are planned for
inclusion in the study.

This is a multi-center, randomized, double-blind, active- and placebo-controlled,
parallel-group study. There is a screening period of up to 28 days, a 52 week double-blind
treatment period, and a 12 week post-treatment follow-up period.
Trial website
https://clinicaltrials.gov/show/NCT03580356
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
novartis.email@novartis.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03580356