Clinical Trials List
Protocol NumberCQGE031C2303
NCT Number(ClinicalTrials.gov Identfier)NCT03580356
2018-09-01 - 2022-08-03
Phase III
Recruiting3
ICD-10L50
Urticaria
ICD-9708.8
Other specified urticaria
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
-
Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
-
Sponsor
Novartis Pharmaceuticals
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 林靖才 Division of Rheumatology
- 周吟怡 Division of Rheumatology
- WEN-NAN HUANG Division of Rheumatology
- 吳沂達 Division of Rheumatology
- 謝佳偉 Division of Rheumatology
- Yi-Ming Chen Division of Rheumatology
- 洪維廷 Division of Rheumatology
- 譚國棟 Division of Rheumatology
The Actual Total Number of Participants Enrolled
0 Recruiting
Linkou Chang Gung Medical Foundation
Taiwan National PI
黃毓惠
Co-Principal Investigator
- Chin-Yi Yang Division of Dermatology
- 林怡廷 Division of Dermatology
- Chung-Yao Hsu Division of Dermatology
- Ya-Ching Chang Division of Dermatology
- Wen-Hung Chung Division of Dermatology
The Actual Total Number of Participants Enrolled
13 Recruiting
Audit
None
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Chronic Spontaneous Urticaria (CSU)
Objectives
Primary objective
The primary objective of the study is to demonstrate that ligelizumab (72 mg q4w and/or 120
mg q4w) is superior to placebo and superior to omalizumab 300 mg q4w in change from
baseline in UAS7 at Week 12
Secondary Objective
To demonstrate that a greater proportion of subjects achieve UAS7 = 0 at Week 12 who are
treated with ligelizumab 72 mg q4w and/or 120 mg q4w compared to placebo-treated subjects
and compared with omalizumab 300 mg q4w treated subjects
To demonstrate the superiority of ligelizumab 72 mg q4w and/or 120 mg q4w treated subjects
with respect to a reduction from baseline in the weekly itch severity score at Week 12
compared to placebo-treated subjects and omalizumab 300 mg q4w treated subjects
To demonstrate that a greater proportion of subjects who are treated with ligelizumab 72 mg
q4w and/or 120 mg q4w achieve DLQI = 0-1 at Week 12 compared to placebo-treated subjects
and omalizumab 300 mg q4w treated subjects
To demonstrate that the ligelizumab 72 mg q4w and/or 120 mg q4w treated subjects have a
longer angioedema occurrence-free period compared with placebo-treated subjects and
omalizumab 300 mg q4w treated subjects.
To demonstrate the safety and tolerability of ligelizumab 72 mg q4w and 120 mg q4w
Test Drug
QGE031/ligelizumab
Active Ingredient
QGE031/ligelizumab
Dosage Form
solution for injection
Dosage
120mg/ml
Endpoints
Primary endpoint(s):
Absolute change from baseline in UAS7 at Week 12
Secondary endpoints:
Complete absence of hives and itch at Week 12, assessed as percentage of subjects achieving
UAS7 = 0
Improvement of severity of itch, assessed as absolute change from baseline in ISS7 score at
TW English Synopsis version 01, 10-May-2018
Based on Protocol V00, release date: 20-Mar-2018
Page | 3
Week 12
No impact on subjects quality of life at Week 12, assessed as % of subjects achieving DLQI =
0-1
Cumulative number of weeks that subjects achieve AAS7 = 0 responses between baseline and
Week 12
Occurrence of treatment emergent adverse events during the study
Occurrence of treatment emergent serious adverse events during the study
Absolute change from baseline in UAS7 at Week 12
Secondary endpoints:
Complete absence of hives and itch at Week 12, assessed as percentage of subjects achieving
UAS7 = 0
Improvement of severity of itch, assessed as absolute change from baseline in ISS7 score at
TW English Synopsis version 01, 10-May-2018
Based on Protocol V00, release date: 20-Mar-2018
Page | 3
Week 12
No impact on subjects quality of life at Week 12, assessed as % of subjects achieving DLQI =
0-1
Cumulative number of weeks that subjects achieve AAS7 = 0 responses between baseline and
Week 12
Occurrence of treatment emergent adverse events during the study
Occurrence of treatment emergent serious adverse events during the study
Inclution Criteria
Inclusion criteria
Subjects eligible for inclusion in this study must meet all of the following 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 <18 years of age, will be in 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.
Subjects eligible for inclusion in this study must meet all of the following 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 <18 years of age, will be in 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
Exclusion criteria
Subjects meeting any of the following criteria are not eligible for inclusion in this study.
No additional exclusions may be applied by the investigator, in order to ensure that the study
population will be representative of all eligible subjects.
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 (see
Section 8.4.3). 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.
12. Inability to comply with study and follow-up procedures.
13. Use of prohibited treatment detailed in protocol (Table 6-2).
14. Contraindications to or hypersensitivity to fexofenadine, loratadine, cetirizine, rupatadine,
epinephrine or any of their ingredients.
15. Documented history of anaphylaxis.
16. History of malignancy of any organ system within the past 5 years (except for basal cell
carcinoma or actinic keratoses or Bowen disease (carcinoma in situ) that have been treated, with no
evidence of recurrence in the past 12 weeks; carcinoma in situ of the cervix or non-invasive malignant
colon polyps that have been removed).
17. Presence of clinically significant cardiovascular (such as but not limited to myocardial
infarction, unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, arrhythmiaand
uncontrolled hypertension within 12 months prior to Visit 1), neurological, psychiatric, metabolic or
other pathological conditions (such as but not limited to cerebrovascular disease, neurodegenerative or
other neurological diseases, uncontrolled hypo- and hyperthyroidism and other autoimmune diseases,
hypokalemia, hyperadrenergic state or ophthalmologic disorder) that could interfere with or
compromise the safety of the subjects, interfere with evaluation or interpretation of the study results,
or preclude completion of the study.
18. Medical examination or laboratory findings that suggest the possibility of decompensation of
co-existing conditions for the duration of the study. Any items that are cause for uncertainty will be
reviewed with the investigator.
19. History of, or current treatment for, hepatic disease including but not limited to acute or
TW English Synopsis version 01, 10-May-2018
Based on Protocol V00, release date: 20-Mar-2018
Page | 6
chronic hepatitis, cirrhosis or hepatic failure or AST/ALT levels or INR of more than 1.5 x upper limit
of normal (ULN) at Visit 1.
20. History of renal disease or creatinine level above 1.5x ULN at Visit 1.
21. Platelets < 100 000/μL at Visit 1.
22. History of long QT syndrome or whose QTcF (Fridericia) measured at Visit 1 is prolonged (>
450 ms for males or > 460 ms for females) and confirmed by a central assessor (these subjects should
not be rescreened).
23. Pregnant or nursing (lactating) women.
24. Female subjects, including adolescent females of 12 to less than 18 years of age, of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are
using basic methods of contraception for the duration of the study (approx. 4 months, i.e. 5 half-lives,
after last dose of ligelizumab or omalizumab). Basic contraception methods include:
a. Total abstinence (when this is in line with the preferred and usual lifestyle of the
subject). Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods)
and withdrawal are not acceptable methods of contraception
b. Female sterilization (surgical bilateral oophorectomy with or without hysterectomy),
total hysterectomy or tubal ligation at least 6 weeks before taking investigational drug. In case
of oophorectomy alone, only when the reproductive status of the woman has been confirmed
by follow-up hormone level assessment
c. Male sterilization (at least 6 months prior to screening). For female subjects on the
study, the vasectomized male partner should be the sole partner for that subject
d. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
cervical/vault caps). For UK: with spermicidal foam/gel/film/cream/ vaginal suppository
e. Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of
contraception or other forms of hormonal contraception that have comparable efficacy (failure
rate < 1%), for example hormone vaginal ring or transdermal hormone contraception or
placement of an intrauterine device (IUD) or intrauterine system (IUS)
In case of use of oral contraception women should have been stable on the same pill for a minimum of
3 months before taking investigational drug.
Women are considered post-menopausal and not of child bearing potential if they have had 12 months
of natural (spontaneous) amenorrhea with an appropriate clinical profile (eg, age appropriate, history
of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy),
total hysterectomy or tubal ligation at least 6 weeks ago. In the case of oophorectomy alone, only
when the reproductive status of the woman has been confirmed by follow-up hormone level
assessment is she considered not of child bearing potential.
If local regulations deviate from the contraception methods listed above to prevent pregnancy, local
regulations apply and will be described in the ICF.
Subjects meeting any of the following criteria are not eligible for inclusion in this study.
No additional exclusions may be applied by the investigator, in order to ensure that the study
population will be representative of all eligible subjects.
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 (see
Section 8.4.3). 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.
12. Inability to comply with study and follow-up procedures.
13. Use of prohibited treatment detailed in protocol (Table 6-2).
14. Contraindications to or hypersensitivity to fexofenadine, loratadine, cetirizine, rupatadine,
epinephrine or any of their ingredients.
15. Documented history of anaphylaxis.
16. History of malignancy of any organ system within the past 5 years (except for basal cell
carcinoma or actinic keratoses or Bowen disease (carcinoma in situ) that have been treated, with no
evidence of recurrence in the past 12 weeks; carcinoma in situ of the cervix or non-invasive malignant
colon polyps that have been removed).
17. Presence of clinically significant cardiovascular (such as but not limited to myocardial
infarction, unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, arrhythmiaand
uncontrolled hypertension within 12 months prior to Visit 1), neurological, psychiatric, metabolic or
other pathological conditions (such as but not limited to cerebrovascular disease, neurodegenerative or
other neurological diseases, uncontrolled hypo- and hyperthyroidism and other autoimmune diseases,
hypokalemia, hyperadrenergic state or ophthalmologic disorder) that could interfere with or
compromise the safety of the subjects, interfere with evaluation or interpretation of the study results,
or preclude completion of the study.
18. Medical examination or laboratory findings that suggest the possibility of decompensation of
co-existing conditions for the duration of the study. Any items that are cause for uncertainty will be
reviewed with the investigator.
19. History of, or current treatment for, hepatic disease including but not limited to acute or
TW English Synopsis version 01, 10-May-2018
Based on Protocol V00, release date: 20-Mar-2018
Page | 6
chronic hepatitis, cirrhosis or hepatic failure or AST/ALT levels or INR of more than 1.5 x upper limit
of normal (ULN) at Visit 1.
20. History of renal disease or creatinine level above 1.5x ULN at Visit 1.
21. Platelets < 100 000/μL at Visit 1.
22. History of long QT syndrome or whose QTcF (Fridericia) measured at Visit 1 is prolonged (>
450 ms for males or > 460 ms for females) and confirmed by a central assessor (these subjects should
not be rescreened).
23. Pregnant or nursing (lactating) women.
24. Female subjects, including adolescent females of 12 to less than 18 years of age, of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are
using basic methods of contraception for the duration of the study (approx. 4 months, i.e. 5 half-lives,
after last dose of ligelizumab or omalizumab). Basic contraception methods include:
a. Total abstinence (when this is in line with the preferred and usual lifestyle of the
subject). Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods)
and withdrawal are not acceptable methods of contraception
b. Female sterilization (surgical bilateral oophorectomy with or without hysterectomy),
total hysterectomy or tubal ligation at least 6 weeks before taking investigational drug. In case
of oophorectomy alone, only when the reproductive status of the woman has been confirmed
by follow-up hormone level assessment
c. Male sterilization (at least 6 months prior to screening). For female subjects on the
study, the vasectomized male partner should be the sole partner for that subject
d. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
cervical/vault caps). For UK: with spermicidal foam/gel/film/cream/ vaginal suppository
e. Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of
contraception or other forms of hormonal contraception that have comparable efficacy (failure
rate < 1%), for example hormone vaginal ring or transdermal hormone contraception or
placement of an intrauterine device (IUD) or intrauterine system (IUS)
In case of use of oral contraception women should have been stable on the same pill for a minimum of
3 months before taking investigational drug.
Women are considered post-menopausal and not of child bearing potential if they have had 12 months
of natural (spontaneous) amenorrhea with an appropriate clinical profile (eg, age appropriate, history
of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy),
total hysterectomy or tubal ligation at least 6 weeks ago. In the case of oophorectomy alone, only
when the reproductive status of the woman has been confirmed by follow-up hormone level
assessment is she considered not of child bearing potential.
If local regulations deviate from the contraception methods listed above to prevent pregnancy, local
regulations apply and will be described in the ICF.
The Estimated Number of Participants
-
Taiwan
50 participants
-
Global
1050 participants
