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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

PHRR190115-002037

CQGE031C2303

2018-CT0456

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 

This is a Phase III 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.

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-AH. Of these, approximately 1000 adults and 50 adolescents are planned for inclusion in the study.

Start Date Duration in Months Target Completion Date Actual Completion Date
2019-04-03 24 2021-04-03 0000-00-00

Ongoing

Institution Classification Region LTO #
Novartis Healthcare Philippines, Inc. Private Business NCR 3000006283930
Institution Classification Region LTO #
PAREXEL Clinical Research (Philippines) Ltd. Corp. Private Business NCR CDRR-NCR-CRO-4
Institution Region
Novartis Healthcare Philippines, Inc. NCR
Name E-Mail Institution and Institution Address
Anna Liza Calingasin anna_liza.calingasin@novartis.com 5/F Ayala North Exchange Tower 1 Salcedo corner Amorsolo Streets Legaspi Village, Makati City 1229 Philippines
Name E-Mail Institution and Institution Address
Ivy Emily Peneyro-Vergara, MD ivy_emily.peneyro-vergara@novartis.com 5/F Ayala North Exchange Tower 1 Salcedo corner Amorsolo Streets Legaspi Village, Makati City 1229 Philippines
Name Expertise Affiliation
Celeste C. Tolentino, MD Allergology Mary Mediatrix Medical Center
Jenifer R. Otadoy-Agustin, MD Allergology University of Perpetual Help DALTA Medical Center
Ma. Lourdes Anna M. Nebrida-Idea, MD Dermatolgist St. Luke's Medical Center - Quezon City
Maria Deanna Ramiscal, MD Dermatologist St. Luke's Medical Center - Quezon City
Michelle Joy De Vera, MD Allergologist The Medical City
Vermen Verallo-Rowell, MD Dermatologist VMV Skin Research Centre + Clinics
Project Location Institutional Ethics Review Board
Mary Mediatrix Medical Center Mary Mediatrix Medical Center Research Ethics Review Committee
University of Perpetual Help DALTA Medical Center University of Perpetual Help DALTA Medical Center Ethics Review Committee
St. Luke's Medical Center - Quezon City St. Luke's Medical Center Institutional Ethics Review Board
St. Luke's Medical Center - Quezon City St. Luke's Medical Center Institutional Ethics Review Board
The Medical City The Medical City - Institutional Review Board
VMV Skin Research Centre + Clinics VMV Skin Research Centre + Clinics - Institutional Review Board

Chronic spontaneous Urticaria (CSU) 

Absolute change from baseline in UAS7 at Week 12

1. Complete absence of hives and itch at Week 12, assessed as percentage of subjects achieving UAS7 = 0
2. 
Improvement of severity of itch, assessed as absolute change from baseline in ISS7 score at Week 12
3. 
No impact on subjects quality of life at Week 12, assessed as % of subjects achieving DLQI = 0-1
4. 
Cumulative number of weeks that subjects achieve AAS7 = 0 responses between baseline and Week 12
5. 
Occurrence of treatment emergent adverse events during the study
6. Occurrence of treatment emergent serious adverse
events during the study

Completed

  • Argentina
  • Australia
  • Belgium
  • Brazil
  • Chile
  • Egypt
  • Estonia
  • Finland
  • France
  • Germany
  • India
  • Israel
  • Italy
  • Japan
  • Lebanon
  • Mexico
  • Netherlands
  • Norway
  • Philippines
  • Poland
  • Romania
  • Russia
  • Slovakia
  • Spain
  • Taiwan
  • Tunisia
  • United States
  • Vietnam

Clinical Trial

CQGE031C2303

20180807121837

2018-10-31

0000-00-00

20

17

17 patients were randomized in the trial. Sites were not able to reach the commitment.

2019-04-03

INCLUSION CRITERIA

1. Signed informed consent must be obtained prior to participation in the study.
2. Subject’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.
3. Male and female subjects ≥ 12 years of age at the time of screening.
(NOTE: Recruitment of adolescent subjects, ≥ 12 to
accordance with local requirements).
4. CSU diagnosis for ≥ 6 months.
5. Diagnosis of CSU refractory to H1-AH at approved doses at the time of randomization, as
defined by all of the following:
a. 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
b. UAS7 score (range 042)  16 and HSS7 score (range 021)  8 during the 7 days
prior to randomization (Visit 110, Day 1)
c. Subjects must be on H1-AH at only approved doses for treatment of CSU starting at
Visit 1 (Day -28 to Day -14)
6. Willing and able to complete a daily symptom eDiary for the duration of the study and
adhere to the study visit schedules.
7. Subjects must not have had any missing eDiary entries in the 7 days (twice a day) prior to
randomization (Day 1, Visit 110), i.e. 14 eDiary entries required. Rescreening may be
considered only once.
EXCLUSION CRITERIA
1. Use of other investigational drugs within 5 half-lives, or within 30 days (for small molecules) prior to Visit 1 or until the expected pharmacodynamic effect has returned to baseline (for biologics), whichever is longer.
2. 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).
3. 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.
4. 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).
5. 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 organisms, the subject will not be randomized and will not be allowed to rescreen.
6. Any other skin disease associated with chronic itching that might influence, in the
investigators opinion, the study evaluations and results (eg, atopic dermatitis, bullous
pemphigoid, dermatitis herpetiformis, senile pruritus, etc.).
7. Prior exposure to ligelizumab or omalizumab.
8. Any H2 antihistamine use after Visit 1.
9. Any LTRA (montelukast or zafirlukast) use after Visit 1.
10. Any H1 antihistamines use at greater than approved doses after Visit 1.
11. History or evidence of ongoing alcohol or drug abuse, within the last 6 months prior to
randomization.

Interventional

ligelizumab (QGE031), omalizumab

Ligelizumab (QGE031) is a humanized IgG-type monoclonal antibody that binds to human
IgE with higher affinity than omalizumab. Upon binding to specific epitopes in the C3 region
of IgE, ligelizumab is able to block the interaction of IgE with both the high and low affinity
IgE receptors (FcεRI and FcεRII). Ligelizumab does not mediate IgE receptor cross-linking
and consequent histamine release (i.e. is non-activating). This overall mechanism of action
(MoA) is shared with omalizumab (Chang et al 2015).

Omalizumab, a less potent monoclonal antibody than ligelizumab which also
targets immunoglobulin E (IgE), has been approved in several countries including those in the
European Union, the United States, Japan and Switzerland as add-on therapy in patients with
CSU with symptoms despite treatment with antihistamines. Omalizumab improved the signs
and symptoms of urticaria (i.e. hives and itch) in patients who failed treatment with H1-
antihistamines as well as in those who failed treatment with a combination of H1- and H2-
antihistamines and a LTRA (Gober et al 2008, Kaplan et al 2008, Maurer et al 2013, Kaplan
et al 2013).

Date Amendment Classification Reason
2020-03-10 Amendments related to the protocol Informed consent

Randomized

Double Blind

Blinding will be maintained using the following methods: 1. Randomization data are kept strictly confidential until the time of unblinding, and will not be accessible by anyone else involved in the study with the following exceptions:  Bioanalyst (PK): to enable identification of samples from the ligelizumab treatment arms of the study to facilitate bioanalysis;  Independent personnel (external to Novartis) involved in monitoring anaphylaxis, neoplastic and cerebro-cardiovascular events (Adjudication Committee members), if needed; and  An independent Data Monitoring Committee (DMC; see Section 10.2.3) and the independent statistician supporting the DMC activities (Table 6-4). 2. The following measures will be applied to keep the subject and study personnel blinded despite differences of the investigational treatments in appearance, viscosity and volume:  The study drug must be prepared by an independent unblinded pharmacist (or authorized delegate) and administered by an independent unblinded administrator who are both not involved in any of the study assessments. If an unblinded pharmacist is not available, preparation and administration of drug may also be performed by a single independent unblinded site person if he/she is authorized to do both.  Preparation of the investigational drug must be done in a separate space/room where subjects and study personnel have no access during time of preparation.  To blind the liquid volume in the syringe, the syringe must be covered by a strip of opaque tape. The differences in length of the syringe plunger, related to the differences in the volume, should also be covered by the way of administration (see Pharmacist Manual).  The prepared syringes must be placed on a tray which is covered by an opaque towel to ensure the syringes are not visible to the subject at any time.  The independent unblinded authorized site persons (pharmacist/administrator) should not communicate the appearance, the volume and any perceived sensation associated with the administration of the investigational drug.  The subject will be instructed to look away from the tray of prepared syringes whenever the tray is uncovered and from the injection site.

Parallel

The purpose of this study is to establish efficacy and safety of ligelizumab in adult and
adolescent subjects with CSU, who remain symptomatic despite standard of care treatment by
demonstrating better efficacy over Xolair® (omalizumab) when added to H1-antihistamines at
approved doses, over 12 months of treatment and a follow-up period of 12 weeks.
Due to the relatively low number of adolescent subjects planned for inclusion in this study,
efficacy and safety data for these subjects will be investigated in separate pooled multiple
study extrapolation analyses with the objective of proposing a posology for the treatment of
adolescent patients.

Phase III

Utilization Utilization Info
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