A study to investigate the use of benralizumab in patients with Chronic Spontaneous Urticaria Who are Symptomatic Despite the Use of Antihistamines (ARROYO)  (ARROYO)

Recruitment Status:
Recruiting

Sponsor:
AstraZeneca

Collaborator:
IQVIA

Information Provided by (Responsible Party):
AstraZeneca

ClinicalTrials.gov Identifier:
NCT04612725

Verification:
Verified 01 April 2021   by AstraZeneca

History of Changes:
ClinicalTrials.gov

Purpose

The purpose of this study is to investigate the use of benralizumab is effective in the treatment of chronic spontaneous urticaria (CSU) who are symptomatic despite the use of antihistamines.

Official Title:A Phase 2b Multinational, Randomised, Double-blind, Parallel- group, 24-week Placebo-controlled Study with 28-week Extension to Investigate the Use of Benralizumab in Patients with Chronic Spontaneous Urticaria Who are Symptomatic Despite the Use of Antihistamines (ARROYO)
Study Type:Interventional
Overall Recruitment Status:Recruiting
Study Start Date:27 October 2020
Study Start Date Type:Actual
Primary Completion Date:02 March 2022
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
ConditionInterventionPhase
Chronic Spontaneous Urticaria
Biological/Vaccine: Benralizumab
Biological/Vaccine: Placebo and Benralizumab
Phase 2
Ages Eligible for Study: 18 Years  to 130 Years
Genders Eligible for Study: Both
Gender Based: No
Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:
Informed Consent/Age/Gender
1. Provision of the signed and dated written informed consent of the participant prior to any mandatory study-specific procedures, sampling, and analyses.
2. Adult participants≥18 years of age at the time of signing the Informed Consent Form (ICF).

Type of Participants and Disease
3. Physician-confirmed diagnosis of CSU (also known as chronic idiopathic urticaria) for at least 6 months prior to screening (Visit 1).
4. Presence of pruritus and wheals for at least 6 consecutive weeks prior to screening (Visit 1), despite receiving standard of care, which may include second generation H1 antihistamines (at approved or up to 4-times approved doses) as monotherapy or in combination with LTRAs and/or H2 blockers.
5. Symptomatic during run-in, defined by the following:
(a) UAS7 total score of ≥ 16 with an ISS7 of ≥ 8, during the 7 days prior to randomisation (Visit 2)
(b) In-clinic UAS total score of ≥ 4 on at least one of the screening days.
6. Willing to use a second-generation H1 antihistamine at the approved dose and as monotherapy from the screening visit (Visit 1) until the end of the study.
7. Participants must complete daily PRO assessments and meet the following compliance criteria:
(a) Complete at least 80% of daily PRO assessments between Visit 1 and Visit 2 and
(b) Complete at least 6 of 7 daily PRO assessments in the 7 days prior to Visit 2.
8. Compliance with the locally-approved dose of antihistamine, maintained at randomisation.
Reproduction
9. Women of childbearing potential (WOCBP) must agree to use a highly effective method of birth control (confirmed by the Investigator) from randomisation, throughout the study duration, and within12 weeks after last dose of IP and have a negative serum pregnancy test result on Visit 1. Highly effective methods of birth control include:
(a) Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal.
(b) Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable.
(c) Intrauterine device.
(d) Intrauterine hormone-releasing system.
(e) Bilateral tubal occlusion or ligation.
(f) Sexual abstinence, ie, refraining from heterosexual intercourse (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant).
(g) Vasectomised sexual partner (provided that partner is the sole sexual partner of the WOCBP study participant and that the vasectomised partner has received medical assessment of the surgical success).
10. Women not of childbearing potential are defined as women who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrhoeic for≥12 months prior to the planned date of randomisation without an alternative medical cause. The following age-specific requirements apply:
(a) Women<50 years old will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and follicle-stimulating hormone (FSH) levels in the postmenopausal range. Until FSH is documented to be within menopausal range, the participant should be treated as a WOCBP.
(b) Women≥50 years old will be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment.

Exclusion Criteria:
Medical Conditions
1. Participants with predominant inducible urticaria, ie, urticaria that is predominantly due to a clearly defined stimulus (eg, pressure [dermographism], delayed pressure, cold, heat, sunlight, vibration, water, physical exercise, or increased body temperature [cholinergic]).
2. Participants with diseases, other than chronic urticaria, with urticaria or angioedema symptoms such as urticaria vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema (eg, due to C1-inhibitor deficiency). Additionally, any other skin disease associated with chronic itching and/or skin lesions that, in the investigators opinion, might influence the study evaluations and results (eg, atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.).
3. Current malignancy, or history of malignancy, with the exception of: (a) Participants who have had basal cell carcinoma, localised squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that the participant is in remission and curative therapy was completed at least 12 months prior to the date informed consent, was obtained. (b) Participants who have had other malignancies are eligible provided that the participant is in remission and curative therapy was completed at least 5 years prior to the date informed consent, was obtained.
4. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could: (a) Affect the safety of the participant throughout the study (b) Influence the findings of the studies or their interpretations (c) Impede the participant’s ability to complete the entire duration of study.
5. History of anaphylaxis to any biologic therapy or vaccine.
6. A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with,or has failed to respond to standard of care therapy.
7. Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening/run-in period which, in the opinion of the Investigator, may put the participant at risk because of his/her participation in the study, or may influence the results of the study, or the participant’s ability to complete entire duration of the study.
8. Current active liver disease:
(a) Chronic stable hepatitis B andC (including positive testing for hepatitis B surface antigen [HBsAg] or hepatitis C antibody), or other stable chronic liver disease are acceptable if participant otherwise meets eligibility criteria. Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice, or cirrhosis.
(b) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level≥3 times the upper limit of normal (ULN), confirmed by repeated testing during the run-in period. Transient increase of AST/ALT level that resolves by the time of randomisationis acceptable if in the Investigator’s opinion the participant does not have an active liver disease and meets other eligibility criteria.
9. A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.
Prior/concomitant Therapy
10. Doses administered daily or every other day for 5 or more consecutive days of systemic or topical corticosteroids, hydroxychloroquine, methotrexate, cyclosporine, cyclophosphamide, or (IV) immunoglobulin within 30 days before day -14.
11. Use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid, oral corticosteroid, or any experimental anti-inflammatory therapy) within 3 months prior to the date informed consent is obtained.Short-term treatmentsincluding systemicsteroids for CSU related angioedema may be an exceptionand cases should be discussed with sponsor/study physician.
Other
12. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained
13. Receipt of any marketed (eg, omalizumab) or investigational biologic within 4 months or 5 half-lives prior to the date informed consent is obtained, whichever is longer.
14. Receipt of live attenuated vaccines 30 days prior to the date of randomisation
15. Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to the date informed consent is obtained, whichever is longer 17 Previously received benralizumab (MEDI-563, FASENRA)
16. Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to the date informed consent is obtained, whichever is longer
17. Previously received benralizumab (MEDI-563, FASENRA)
18. Change to allergen immunotherapy or new allergen immunotherapy within 30 days prior to the date of informed consent and anticipated changes in immunotherapy throughout the study
19. Planned major surgical procedures during the conduct of the study
20. Previous randomisationin the present study
21. Concurrent enrollment in another clinical trial
22. AstraZeneca staff involved in the planning and/or conduct of the study
23. For women only: Currently pregnant, breastfeeding, or lactating women (a) A serum pregnancy test will be done for WOCBP at Visit 1 and a urine pregnancy test must be performed for WOCBP at each treatment visit prior to IP administration. A positive urine test result must be confirmed with a serum pregnancy test. If serum test is positive, the participant should be excluded.


Contacts

Contact: AstraZeneca Clinical  Study Information Center   1-877-240-9479    information.center@astrazeneca.com  

Sponsors and Collaborators

AstraZeneca
IQVIA

Investigators

Principal Investigator: Sabine  Altrichter , MD   Charite Universitaetsmedizin Berlin - Campus Charite Mitte

Locations

CountryLocationFacilityContactStatus
United States of America , OHResearch Site Cincinnati, OH, United States of America, 45231Recruiting
United States of America , OHResearch Site Cincinnati, OH, United States of America, 45229Not Yet Recruiting
United States of America , CAResearch Site Los Angeles, CA, United States of America, 90025Recruiting
United States of America , CAResearch Site Mission Viejo, CA, United States of America, 92691Recruiting
United States of America , CAResearch Site Newport Beach, CA, United States of America, 92663Recruiting
United States of America , CAResearch Site Westminister, CA, United States of America, 92683Recruiting
United States of America , FLResearch Site Tampa, FL, United States of America, 33606Recruiting
United States of America , AZResearch Site Scottsdale, AZ, United States of America, 85260Recruiting
United States of America , TXResearch Site Austin, TX, United States of America, 78745Recruiting
GermanyResearch Site Berlin, Germany, 10117Not Yet Recruiting
GermanyResearch Site Berlin, Germany, 10789Not Yet Recruiting
GermanyResearch Site Dresden, Germany, 01307Not Yet Recruiting
GermanyResearch Site Leipzig, Germany, 04103Not Yet Recruiting
United States of America , MIResearch Site Ypsilanti, MI, United States of America, 48197Recruiting
United States of America , GAResearch Site Columbus, GA, United States of America, 31904Recruiting
United States of America , OKResearch Site Norman, OK, United States of America, 73071Recruiting
JapanResearch Site Hiroshima-shi, Japan, 734-8551Recruiting
JapanResearch Site Kamimashiki-gun, Japan, 861-3101Recruiting
JapanResearch Site Kawasaki-shi, Japan, 211-0063Recruiting
JapanResearch Site Kobe-shi, Japan, 650-0017Recruiting
JapanResearch Site Sakai-shi, Japan, 593-8324Recruiting
United States of America , FloridaResearch Site Miami, Florida, United States of America, 33173Recruiting
PolandResearch Site Gdańsk, Poland, 80-546Not Yet Recruiting
PolandResearch Site Krakow, Poland, 30-033Not Yet Recruiting
PolandResearch Site Poznan, Poland, 60-529Not Yet Recruiting
PolandResearch Site Poznań, Poland, 60-214Not Yet Recruiting
PolandResearch Site Warszawa, Poland, 02-507Not Yet Recruiting
PolandResearch Site Wrocław, Poland, 50-449Not Yet Recruiting
SpainResearch Site Alicante, Spain, 03010Not Yet Recruiting
SpainResearch Site Barcelona, Spain, 8003Not Yet Recruiting
SpainResearch Site Barcelona, Spain, 08036Not Yet Recruiting
SpainResearch Site Cordoba, Spain, 14004Not Yet Recruiting
SpainResearch Site Madrid, Spain, 28040Not Yet Recruiting
SpainResearch Site Manises, Spain, 46940Not Yet Recruiting
BulgariaResearch Site Haskovo, Bulgaria, 6300Recruiting
BulgariaResearch Site Pleven, Bulgaria, 5800Withdrawn
BulgariaResearch Site Pleven, Bulgaria, 5800Recruiting
BulgariaResearch Site Ruse, Bulgaria, 7013Recruiting
BulgariaResearch Site Sofia, Bulgaria, 1463Not Yet Recruiting
BulgariaResearch Site Sofia, Bulgaria, 1606Recruiting
BulgariaResearch Site Sofia, Bulgaria, 1680Recruiting
BulgariaResearch Site Sofia, Bulgaria, 1000Recruiting
South KoreaResearch Site Gwangju, South Korea, 61469Not Yet Recruiting
South KoreaResearch Site Seongnam-si, South Korea, 13620Not Yet Recruiting
South KoreaResearch Site Seoul, South Korea, 06973Not Yet Recruiting
South KoreaResearch Site Seoul, South Korea, 6591Not Yet Recruiting
South KoreaResearch Site Seoul, South Korea, 03722Not Yet Recruiting

No attachments posted.

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Purpose

The purpose of this study is to investigate the use of benralizumab is effective in the treatment of chronic spontaneous urticaria (CSU) who are symptomatic despite the use of antihistamines.

Official Title:A Phase 2b Multinational, Randomised, Double-blind, Parallel- group, 24-week Placebo-controlled Study with 28-week Extension to Investigate the Use of Benralizumab in Patients with Chronic Spontaneous Urticaria Who are Symptomatic Despite the Use of Antihistamines (ARROYO)
Study Type:Interventional
Overall Recruitment Status:Recruiting
Study Start Date:27 October 2020
Study Start Date Type:Actual
Primary Completion Date:02 March 2022
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
ConditionInterventionPhase
Chronic Spontaneous Urticaria
Biological/Vaccine: Benralizumab
Biological/Vaccine: Placebo and Benralizumab
Phase 2
Ages Eligible for Study: 18 Years  to 130 Years
Genders Eligible for Study: Both
Gender Based: No
Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:
Informed Consent/Age/Gender
1. Provision of the signed and dated written informed consent of the participant prior to any mandatory study-specific procedures, sampling, and analyses.
2. Adult participants≥18 years of age at the time of signing the Informed Consent Form (ICF).

Type of Participants and Disease
3. Physician-confirmed diagnosis of CSU (also known as chronic idiopathic urticaria) for at least 6 months prior to screening (Visit 1).
4. Presence of pruritus and wheals for at least 6 consecutive weeks prior to screening (Visit 1), despite receiving standard of care, which may include second generation H1 antihistamines (at approved or up to 4-times approved doses) as monotherapy or in combination with LTRAs and/or H2 blockers.
5. Symptomatic during run-in, defined by the following:
(a) UAS7 total score of ≥ 16 with an ISS7 of ≥ 8, during the 7 days prior to randomisation (Visit 2)
(b) In-clinic UAS total score of ≥ 4 on at least one of the screening days.
6. Willing to use a second-generation H1 antihistamine at the approved dose and as monotherapy from the screening visit (Visit 1) until the end of the study.
7. Participants must complete daily PRO assessments and meet the following compliance criteria:
(a) Complete at least 80% of daily PRO assessments between Visit 1 and Visit 2 and
(b) Complete at least 6 of 7 daily PRO assessments in the 7 days prior to Visit 2.
8. Compliance with the locally-approved dose of antihistamine, maintained at randomisation.
Reproduction
9. Women of childbearing potential (WOCBP) must agree to use a highly effective method of birth control (confirmed by the Investigator) from randomisation, throughout the study duration, and within12 weeks after last dose of IP and have a negative serum pregnancy test result on Visit 1. Highly effective methods of birth control include:
(a) Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal.
(b) Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable.
(c) Intrauterine device.
(d) Intrauterine hormone-releasing system.
(e) Bilateral tubal occlusion or ligation.
(f) Sexual abstinence, ie, refraining from heterosexual intercourse (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant).
(g) Vasectomised sexual partner (provided that partner is the sole sexual partner of the WOCBP study participant and that the vasectomised partner has received medical assessment of the surgical success).
10. Women not of childbearing potential are defined as women who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrhoeic for≥12 months prior to the planned date of randomisation without an alternative medical cause. The following age-specific requirements apply:
(a) Women<50 years old will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and follicle-stimulating hormone (FSH) levels in the postmenopausal range. Until FSH is documented to be within menopausal range, the participant should be treated as a WOCBP.
(b) Women≥50 years old will be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment.

Exclusion Criteria:
Medical Conditions
1. Participants with predominant inducible urticaria, ie, urticaria that is predominantly due to a clearly defined stimulus (eg, pressure [dermographism], delayed pressure, cold, heat, sunlight, vibration, water, physical exercise, or increased body temperature [cholinergic]).
2. Participants with diseases, other than chronic urticaria, with urticaria or angioedema symptoms such as urticaria vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema (eg, due to C1-inhibitor deficiency). Additionally, any other skin disease associated with chronic itching and/or skin lesions that, in the investigators opinion, might influence the study evaluations and results (eg, atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.).
3. Current malignancy, or history of malignancy, with the exception of: (a) Participants who have had basal cell carcinoma, localised squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that the participant is in remission and curative therapy was completed at least 12 months prior to the date informed consent, was obtained. (b) Participants who have had other malignancies are eligible provided that the participant is in remission and curative therapy was completed at least 5 years prior to the date informed consent, was obtained.
4. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could: (a) Affect the safety of the participant throughout the study (b) Influence the findings of the studies or their interpretations (c) Impede the participant’s ability to complete the entire duration of study.
5. History of anaphylaxis to any biologic therapy or vaccine.
6. A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with,or has failed to respond to standard of care therapy.
7. Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening/run-in period which, in the opinion of the Investigator, may put the participant at risk because of his/her participation in the study, or may influence the results of the study, or the participant’s ability to complete entire duration of the study.
8. Current active liver disease:
(a) Chronic stable hepatitis B andC (including positive testing for hepatitis B surface antigen [HBsAg] or hepatitis C antibody), or other stable chronic liver disease are acceptable if participant otherwise meets eligibility criteria. Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice, or cirrhosis.
(b) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level≥3 times the upper limit of normal (ULN), confirmed by repeated testing during the run-in period. Transient increase of AST/ALT level that resolves by the time of randomisationis acceptable if in the Investigator’s opinion the participant does not have an active liver disease and meets other eligibility criteria.
9. A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.
Prior/concomitant Therapy
10. Doses administered daily or every other day for 5 or more consecutive days of systemic or topical corticosteroids, hydroxychloroquine, methotrexate, cyclosporine, cyclophosphamide, or (IV) immunoglobulin within 30 days before day -14.
11. Use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid, oral corticosteroid, or any experimental anti-inflammatory therapy) within 3 months prior to the date informed consent is obtained.Short-term treatmentsincluding systemicsteroids for CSU related angioedema may be an exceptionand cases should be discussed with sponsor/study physician.
Other
12. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained
13. Receipt of any marketed (eg, omalizumab) or investigational biologic within 4 months or 5 half-lives prior to the date informed consent is obtained, whichever is longer.
14. Receipt of live attenuated vaccines 30 days prior to the date of randomisation
15. Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to the date informed consent is obtained, whichever is longer 17 Previously received benralizumab (MEDI-563, FASENRA)
16. Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to the date informed consent is obtained, whichever is longer
17. Previously received benralizumab (MEDI-563, FASENRA)
18. Change to allergen immunotherapy or new allergen immunotherapy within 30 days prior to the date of informed consent and anticipated changes in immunotherapy throughout the study
19. Planned major surgical procedures during the conduct of the study
20. Previous randomisationin the present study
21. Concurrent enrollment in another clinical trial
22. AstraZeneca staff involved in the planning and/or conduct of the study
23. For women only: Currently pregnant, breastfeeding, or lactating women (a) A serum pregnancy test will be done for WOCBP at Visit 1 and a urine pregnancy test must be performed for WOCBP at each treatment visit prior to IP administration. A positive urine test result must be confirmed with a serum pregnancy test. If serum test is positive, the participant should be excluded.


Contacts

Contact: AstraZeneca Clinical  Study Information Center   1-877-240-9479    information.center@astrazeneca.com  

Sponsors and Collaborators

AstraZeneca
IQVIA

Investigators

Principal Investigator: Sabine  Altrichter , MD   Charite Universitaetsmedizin Berlin - Campus Charite Mitte

Locations

CountryLocationFacilityContactStatus
United States of America , OHResearch Site Cincinnati, OH, United States of America, 45231Recruiting
United States of America , OHResearch Site Cincinnati, OH, United States of America, 45229Not Yet Recruiting
United States of America , CAResearch Site Los Angeles, CA, United States of America, 90025Recruiting
United States of America , CAResearch Site Mission Viejo, CA, United States of America, 92691Recruiting
United States of America , CAResearch Site Newport Beach, CA, United States of America, 92663Recruiting
United States of America , CAResearch Site Westminister, CA, United States of America, 92683Recruiting
United States of America , FLResearch Site Tampa, FL, United States of America, 33606Recruiting
United States of America , AZResearch Site Scottsdale, AZ, United States of America, 85260Recruiting
United States of America , TXResearch Site Austin, TX, United States of America, 78745Recruiting
GermanyResearch Site Berlin, Germany, 10117Not Yet Recruiting
GermanyResearch Site Berlin, Germany, 10789Not Yet Recruiting
GermanyResearch Site Dresden, Germany, 01307Not Yet Recruiting
GermanyResearch Site Leipzig, Germany, 04103Not Yet Recruiting
United States of America , MIResearch Site Ypsilanti, MI, United States of America, 48197Recruiting
United States of America , GAResearch Site Columbus, GA, United States of America, 31904Recruiting
United States of America , OKResearch Site Norman, OK, United States of America, 73071Recruiting
JapanResearch Site Hiroshima-shi, Japan, 734-8551Recruiting
JapanResearch Site Kamimashiki-gun, Japan, 861-3101Recruiting
JapanResearch Site Kawasaki-shi, Japan, 211-0063Recruiting
JapanResearch Site Kobe-shi, Japan, 650-0017Recruiting
JapanResearch Site Sakai-shi, Japan, 593-8324Recruiting
United States of America , FloridaResearch Site Miami, Florida, United States of America, 33173Recruiting
PolandResearch Site Gdańsk, Poland, 80-546Not Yet Recruiting
PolandResearch Site Krakow, Poland, 30-033Not Yet Recruiting
PolandResearch Site Poznan, Poland, 60-529Not Yet Recruiting
PolandResearch Site Poznań, Poland, 60-214Not Yet Recruiting
PolandResearch Site Warszawa, Poland, 02-507Not Yet Recruiting
PolandResearch Site Wrocław, Poland, 50-449Not Yet Recruiting
SpainResearch Site Alicante, Spain, 03010Not Yet Recruiting
SpainResearch Site Barcelona, Spain, 8003Not Yet Recruiting
SpainResearch Site Barcelona, Spain, 08036Not Yet Recruiting
SpainResearch Site Cordoba, Spain, 14004Not Yet Recruiting
SpainResearch Site Madrid, Spain, 28040Not Yet Recruiting
SpainResearch Site Manises, Spain, 46940Not Yet Recruiting
BulgariaResearch Site Haskovo, Bulgaria, 6300Recruiting
BulgariaResearch Site Pleven, Bulgaria, 5800Withdrawn
BulgariaResearch Site Pleven, Bulgaria, 5800Recruiting
BulgariaResearch Site Ruse, Bulgaria, 7013Recruiting
BulgariaResearch Site Sofia, Bulgaria, 1463Not Yet Recruiting
BulgariaResearch Site Sofia, Bulgaria, 1606Recruiting
BulgariaResearch Site Sofia, Bulgaria, 1680Recruiting
BulgariaResearch Site Sofia, Bulgaria, 1000Recruiting
South KoreaResearch Site Gwangju, South Korea, 61469Not Yet Recruiting
South KoreaResearch Site Seongnam-si, South Korea, 13620Not Yet Recruiting
South KoreaResearch Site Seoul, South Korea, 06973Not Yet Recruiting
South KoreaResearch Site Seoul, South Korea, 6591Not Yet Recruiting
South KoreaResearch Site Seoul, South Korea, 03722Not Yet Recruiting

Oversight


Is FDA regulated intervention: Yes 
Is IND/IDE protocol: Yes 
Section 801 trial: Yes 
IND/IDE Grantor: CBER 
IND/IDE Number: 146828 
Has Expanded Access: No 
U.S. FDA-regulated Drug: Yes 
U.S. FDA-regulated Device: No 

More Information


No publications provided

Responsible Party:AstraZeneca
ClinicalTrials.gov Identifier:NCT04612725
Other Study ID Numbers:D3259C00001

Keywords provided by AstraZeneca
chronic spontaneous urticaria,
skin lesion,
pruritus and wheals

Additional Relevant MeSH terms:
Chronic Spontaneous Urticaria

Primary Outcome Measures:

  • Change from baseline in weekly Itch Severity Score (ISS7) at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue:  ]
    Change from baseline in weekly Itch Severity Score (ISS7) at Week 12 between benralizumab and placebo. The minimum ISS7 is 0 and the maximum is 21, being 21 the most severe score. The baseline ISS7 will be the sum of the ISS during the 7 days prior to day of randomisation. The ISS7 at Week 12 will be the sum of the daily ISS during the previous 7 days.

Secondary Outcome Measures:

  • Change from baseline in Urticaria Activity Score (UAS7) at Week 12 [ Time Frame: Week 12 for all patients ] [ Designated as safety issue:  ]

  • Change from baseline in Urticaria Activity Score (UAS7) at Week 24 [ Time Frame: Week 24 relative to baseline for all patients ] [ Designated as safety issue:  ]

  • Proportion of responders Urticaria Activity Score (UAS7≤6) at Week 12 [ Time Frame: Week 12 for all patients ] [ Designated as safety issue:  ]

  • Change from baseline in weekly hives severity score (HSS7) at Week 12 [ Time Frame: Week 12 for all patients ] [ Designated as safety issue:  ]
    The minimum HSS7 is 0 and the maximum is 21. The baseline HSS7 will be the sum of the HSS during the 7 days prior to day of randomisation. The HSS7 at Week 12 will be the sum of the daily HSS during the previous 7 days.

  • Time to ≥ 5 point decrease (clinically relevant decrease) in Itch Severity Score (ISS7) [ Time Frame: Week 12 for all patients ] [ Designated as safety issue:  ]

  • Proportion of participants with complete Urticaria Activity Score (UAS7) response (Urticaria Activity Score =0) at Week 12 [ Time Frame: Week 12 for all patients ] [ Designated as safety issue:  ]

  • Measures of angioedema activity at Week 12 in patients with angioedema at baseline [ Time Frame: Week 12 for all patients ] [ Designated as safety issue:  ]
    The Urticaria Patient Daily Diary includes a daily yes/no question asking whether the participant experienced angioedema during the past 24 hours. If yes, the participant is asked a follow-up question about how they treated the swelling:
    0 = Did nothing
    1 = Took some prescription or non-prescription medication,
    2 = Called my doctor, nurse or nurse practitioner,
    3 = Went to see my doctor, nurse or nurse practitioner,
    4 = Went to the emergency room at the hospital,
    5 = Was hospitalized.
    The percentage of angioedema free days will be calculated over the past 7 days.

  • Change from baseline in Urticaria Control Test (UCT) at Week 12 [ Time Frame: Week 12 for all patients ] [ Designated as safety issue:  ]
    The minimum and maximum UCT scores are 0 and 16, with 16 points indicating complete disease control. The UCT score will be calculated when all four questions are answered, otherwise the UCT will be missing. A UCT score of <12 shows poorly controlled urticaria, a UCT score of ≥12 presents well controlled urticaria.

  • Change from baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Weeks 12 and 24 [ Time Frame: Week baseline, weeks 12 & 24 for all patients ] [ Designated as safety issue:  ]
    The minimum possible score is defined as 0 and the maximum possible score is defined as 100. Higher scores indicate worse Quality of Life.

  • Change from baseline in Dermatology Life Quality Index (DLQI) at Weeks 12 and 24 [ Time Frame: Week baseline, weeks 12 & 24 for all patients ] [ Designated as safety issue:  ]
    The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.

  • Serum benralizumab concentration and anti-drug antibodies (ADA). [ Time Frame: Week 60 for all patients ] [ Designated as safety issue:  ]

  • Change from baseline in weekly Itch Severity Score (ISS7) at Week 24 [ Time Frame: Week 24 relative to baseline for all patients ] [ Designated as safety issue:  ]
    Change from baseline in weekly Itch Severity Score (ISS7) at Week 24 between benralizumab and placebo. The minimum ISS7 is 0 and the maximum is 21, being 21 the most severe score. The baseline ISS7 will be the sum of the ISS during the 7 days prior to day of randomisation. The ISS7 at Week 24 will be the sum of the daily ISS during the previous 7 days.

  • Proportion of responders (Urticaria Activity Score UAS7≤6) at Week 24 [ Time Frame: Week 24 relative to baseline for all patients ] [ Designated as safety issue:  ]

  • Change from baseline in weekly hives severity score (HSS7) at Week 24 [ Time Frame: Week 24 relative to baseline for all patients ] [ Designated as safety issue:  ]
    The minimum HSS7 is 0 and the maximum is 21. The baseline HSS7 will be the sum of the HSS during the 7 days prior to day of randomisation. The HSS7 at Week 24 will be the sum of the daily HSS during the previous 7 days.

  • Proportion of participants with complete Urticaria Activity Score (UAS7) response (UAS7 =0) at Week 24 [ Time Frame: Week 24 relative to baseline for all patients ] [ Designated as safety issue:  ]

  • Measures of angioedema activity at Week 24 in patients with angioedema at baseline [ Time Frame: Week 24 relative to baseline for all patients ] [ Designated as safety issue:  ]
    The Urticaria Patient Daily Diary includes a daily yes/no question asking whether the participant experienced angioedema during the past 24 hours. If yes, the participant is asked a follow-up question about how they treated the swelling:
    0 = Did nothing
    1 = Took some prescription or non-prescription medication,
    2 = Called my doctor, nurse or nurse practitioner,
    3 = Went to see my doctor, nurse or nurse practitioner,
    4 = Went to the emergency room at the hospital,
    5 = Was hospitalized.
    The percentage of angioedema free days will be calculated over the past 7 days.

  • Change from baseline in Urticaria Control Test (UCT) at Week 24 [ Time Frame: Week 24 relative to baseline for all patients ] [ Designated as safety issue:  ]
    The minimum and maximum UCT scores are 0 and 16, with 16 points indicating complete disease control. The UCT score will be calculated when all four questions are answered, otherwise the UCT will be missing. A UCT score of <12 shows poorly controlled urticaria, a UCT score of ≥12 presents well controlled urticaria.

  • Change from baseline in Itch Severity Score (ISS7) at Week 52 [ Time Frame: Week 52 relative to baseline for all patients ] [ Designated as safety issue:  ]
    Change from baseline in ISS7 at Week 52Itch Severity Score (ISS7) at Week 52 between benralizumab and placebo. The minimum ISS7 is 0 and the maximum is 21, being 21 the most severe score. The baseline ISS7 will be the sum of the ISS during the 7 days prior to day of randomisation. The ISS7 at Week 52 will be the sum of the daily ISS during the previous 7 days.

Other Pre-specified Outcome Measures:

  • [ Time Frame:  ] [ Designated as safety issue:  ]

ArmsAssigned Interventions
Experimental: Benralizumab Arm 1
Benralizumab Dose A regimen A until Week 12, Dose B regimen A until Week 24, and Dose B regimen B during the extension period until Week 52 (n=30)
Biological/Vaccine: Benralizumab
2 induction doses of benralizumab (dose A and B) compared to placebo, and a comparison of maintenance dosing regimens (B vs A) in the 28-week extension period.
Other Name: Benralizumab, Benra, Fasenra
 
Experimental: Benralizumab Arm 2
Benralizumab Dose A regimen A until Week 12, Dose B regimen A until Week 24,and Dose B regimen A during the extension period until Week 52 (n=30)
Biological/Vaccine: Benralizumab
2 induction doses of benralizumab (dose A and B) compared to placebo, and a comparison of maintenance dosing regimens (B vs A) in the 28-week extension period.
Other Name: Benralizumab, Benra, Fasenra
 
Experimental: Benralizumab Arm 3
Benralizumab Dose B regimen A until Week 12, Dose B regimen A until Week 24, and Dose B regimen B during the extension period until Week 52 (n=30)
Biological/Vaccine: Benralizumab
2 induction doses of benralizumab (dose A and B) compared to placebo, and a comparison of maintenance dosing regimens (B vs A) in the 28-week extension period.
Other Name: Benralizumab, Benra, Fasenra
 
Experimental: Benralizumab Arm 4
Benralizumab Dose B regimen A until Week 12, Dose B regimen A until Week 24, and Dose B regimen A during the extension period until Week 52 (n=30)
Biological/Vaccine: Benralizumab
2 induction doses of benralizumab (dose A and B) compared to placebo, and a comparison of maintenance dosing regimens (B vs A) in the 28-week extension period.
Other Name: Benralizumab, Benra, Fasenra
 
Experimental: Placebo and Benralizumab
Placebo regimen A until Week 24, benralizumab Dose B regiment A until Week 36, and Dose B regimen B until Week 52 (n=40).
Biological/Vaccine: Placebo and Benralizumab
2 induction doses of benralizumab (dose A and B) compared to placebo, and a comparison of maintenance dosing regimens (B vs A) in the 28-week extension period.
Other Name: Benralizumab, Benra, Fasenra