Clinical trial NCT04833855: Study to Evaluate Tezepelumab in Adults With Chronic Spontaneous Urticaria
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Dose-Ranging, Phase 2b Study to Evaluate Efficacy and Safety of Tezepelumab for the Treatment of Chronic Spontaneous Urticaria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Spontaneous Urticaria
Keywords: CSU
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2021-04-06
Enrollment: 183
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the effect of tezepelumab on improvement in the Urticaria Activity Score over 7 days (UAS7).


Eligibility criteria: Inclusion Criteria:

* Signed informed consent must be obtained prior to participation in the study.
* Male and female participants ≥ 18 years and ≤ 80 years of age at the time of screening.
* Chronic spontaneous urticaria (CSU) diagnosis for ≥ 6 months at the time of screening.
* CSU inadequately controlled by second generation H1-antihistamines (sgAH) at enrollment, as defined by all of the following:
* The presence of itch and hives for \>= 6 consecutive weeks at any time prior to screening visit 2
* Failure to respond to an sgAH (up to 4 times the approved dose)
* Urticaria Activity Score over 7 days (UAS7) (range 0-42) \>= 16 and Hives Severity Score over 7 days (HSS7) (range 0-21) \>= 8 during the 7 days prior to enrollment
* Participant with CSU who discontinued, is intolerant to, or was an inadequate responder to anti-IgE therapies despite being treated with omalizumab 300 mg every 4 weeks (Q4W) for 6 months or higher doses of omalizumab \> 2 months or another anti-IgE therapy. Note: This criterion is only applicable for anti-IgE-experienced participants.
* Participant willing and able to complete a daily symptom eDiary for the duration of the study and adhere to the study visit schedules.
* Subject must have been on a sgAH at approved or increased doses (up to 4x the approved dose) for treatment of CSU for at least 3 consecutive days immediately prior to the day -14 screening visit (screening visit 2) and must have documented current use on the day of screening visit 1

Exclusion Criteria:

Disease related, including but not limited to:

* Urticaria is solely due to inducible urticaria
* Active dermatologic diseases (or conditions) other than chronic urticaria, with urticaria wheals or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema (eg, due to C1 inhibitor deficiency)
* Any other active skin disease associated with chronic itching that might influence, in the investigator's opinion, the study evaluations and results (eg, atopic dermatitis, dermatitis herpetiformis, senile pruritus, etc.)
* History of a clinically significant infection within 28 days prior to day 1 that, in the opinion of the investigator or medical monitor, might compromise the safety of the participant in the study, interfere with evaluation of the investigational product, or reduce the participants ability to participate in the study.
* Evidence of active tuberculosis (TB) (in the opinion of the investigator), either treated or untreated, or a positive purified protein derivative (PPD) or QuantiFERON-TB Gold Plus (QFT-Plus) test for TB during screening.
* History of malignancy, except for basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy ≥ 12 months prior to screening or other malignancies treated with apparent success with curative therapy ≥ 5 years prior to screening visit 1.
* Subject is unable to complete an electronic patient diary or complete questionnaires, or does not meet the required level of compliance with the eDiary during the 14 days sgAH stabilization period

Other medical conditions

* History or evidence of severe depression, schizophrenia, previous suicide attempts, or suicidal ideation.

Prior/concomitant therapy, including but not limited to:

* Treatment with any biologic products (eg, omalizumab, ligelizumab) within 4 months or 5 half-lives (whichever is longer) prior to screening visit 1
* Routine (daily or every other day for 5 or more consecutive days) use of systemic corticosteroids, systemic hydroxychloroquine, methotrexate, cyclosporine A, cyclophosphamide, tacrolimus, azathioprine, and mycophenolate mofetil within 30 days prior to screening visit 1.
* Major surgery within 8 weeks prior to screening visit 1 or planned inpatient surgery or hospitalization during the study period.
* Receipt of Ig or blood products within 30 days prior to screening visit 1.
* Vaccination with a live or attenuated vaccine within 30 days prior to screening visit 1. Receipt of COVID-19 vaccines and inactive/killed vaccinations (eg, inactive influenza) are allowed, provided the vaccinations are not administered within 7 days before or after any study dosing visit.
* Known hypersensitivity, including severe hypersensitivity reactions and/or history of anaphylactic shock, to any of the products or components to be administered during dosing or to products of similar chemical classes (ie, to murine, chimeric, or human antibodies.

Primary outcomes:
measure: Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Week 16
timeFrame: Baseline and Week 16
Secondary outcomes:
measure: Change From Baseline in ISS Over 7 Days (ISS7) at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in HSS Over 7 Days (HSS7) at Week 16
timeFrame: Baseline and Week 16
measure: Number of Participants With a UAS7 of ≤ 6 (Minimal Residual Disease) at Week 16
timeFrame: Week 16
measure: Number of Participants With a Change From Baseline in UAS7 of ≤ -10 (Minimal Important Difference)
timeFrame: Baseline and Week 16
measure: Number of Participants With a UAS7 = 0 at Week 16 (Complete Response)
timeFrame: Week 16
measure: Number of Participants With ISS7 = 0 at Week 16 (Complete Resolution)
timeFrame: Week 16
measure: Number of Participants With a Change From Baseline in ISS7 of ≤ -5 (Minimal Important Difference)
timeFrame: Baseline and Week 16
measure: Number of Participants With HSS7 = 0 at Week 16 (Complete Resolution)
timeFrame: Week 16
measure: Number of Participants With a Change From Baseline in HSS7 of ≤ -5.5 (Minimal Important Difference)
timeFrame: Baseline and Week 16
measure: Change From Baseline in Weekly Sleep Interference Score (SIS7) at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in Weekly Sleep Quality Score (SQS7): Sum of Daily SQS at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in SQS7: Sum of Average Daily Q1 - Q3 at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in Urticaria Control Test (UCT) Score at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in Weekly Angioedema Activity Score (AAS7) at Week 16
timeFrame: Baseline and Week 16
measure: Number of Cumulative Weeks That Participants Achieved AAS7 = 0 at Week 16 (Angioedema Occurrence Free)
timeFrame: Baseline to Week 16
measure: Change From Baseline in the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in the Dermatology Life Quality Index (DLQI) at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in the Angioedema Quality of Life Questionnaire (AE-QoL) at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in the Angioedema Control Test (AECT) Score at Week 16
timeFrame: Baseline and Week 16
measure: Number of Participants With an AECT Score = 16 at Week 16 (Complete Control)
timeFrame: Baseline and Week 16
measure: Change From Baseline in the Work Productivity and Activity Impairment Questionnaire: Chronic Urticaria (WPAI-CU) Score at Week 16
timeFrame: Baseline and Week 16
measure: Number of Cumulative Days of sgAH Rescue Medication Use From Baseline to Week 16
timeFrame: Baseline to Week 16
measure: Serum Concentration of Tezepelumab
timeFrame: Week 1 pre-dose, Weeks 2, 4, 8, 12, 16, 24, and 32
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 Week 1 to Week 32, up to 32 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Research Center of Alabama
state: Alabama
city: Fountain Valley
country: United States
facility: First OC Dermatology
state: California
city: Laguna Niguel
country: United States
facility: Avance Clinical Trials
state: California
city: Los Angeles
country: United States
facility: Jonathan Corren MD Inc
state: California
city: Los Angeles
country: United States
facility: Dermatology Research Associates
state: California
city: Santa Monica
country: United States
facility: Clinical Science Institute
state: California
city: Colorado Springs
country: United States
facility: Asthma and Allergy Associates PC
state: Colorado
city: Miami Lakes
country: United States
facility: The Community Research of South Florida
state: Florida
city: Sandy Springs
country: United States
facility: Advanced Medical Research PC
state: Georgia
city: Indianapolis
country: United States
facility: Dawes Fretzin Clinical Research Group, LLC
state: Indiana
city: Overland Park
country: United States
facility: Epiphany Dermatology of Kansas, LLC
state: Kansas
city: Lexington
country: United States
facility: Bluegrass Allergy Care
state: Kentucky
city: Louisville
country: United States
facility: Family Allergy and Asthma Research Institute
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Asthma and Allergy Center
state: Maryland
city: Ann Arbor
country: United States
facility: David Fivenson MD Professional Liability Company
state: Michigan
city: Clarkston
country: United States
facility: Clarkston Skin Research
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Medical Center - New Center One
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Cincinnati
country: United States
facility: Bernstein Clinical Research Center LLC
state: Ohio
city: Dublin
country: United States
facility: Aventiv Research Inc
state: Ohio
city: Johnston
country: United States
facility: Clinical Partners LLC
state: Rhode Island
city: Knoxville
country: United States
facility: The Allergy Asthma and Sinus Center, East Tennessee Center for Clinical Research
state: Tennessee
city: Houston
country: United States
facility: Suzanne Bruce and Associates
state: Texas
city: Laredo
country: United States
facility: Cutis Wellness Dermatology and Dermatopathology, PLLC
state: Texas
city: Calgary
country: Canada
facility: Dermatology Research Institute Incorporated
state: Alberta
city: Fredericton
country: Canada
facility: Brunswick Dermatology Centre
state: New Brunswick
city: Hamilton
country: Canada
facility: LEADER Research
state: Ontario
city: Markham
country: Canada
facility: Lynderm Research Inc
state: Ontario
city: Mississauga
country: Canada
facility: Cheema Research Incorporated
state: Ontario
city: Newmarket
country: Canada
facility: Dr. S. K. Siddha Medicine Professional Corporation
state: Ontario
city: Niagara Falls
country: Canada
facility: Allergy Research Canada Incorporated
state: Ontario
city: North York
country: Canada
facility: Gordon Sussman Clinical Research Incorporated
state: Ontario
city: Quebec
country: Canada
facility: Clinique Spécialisée en Allergie de la Capitale
city: Brest
country: France
facility: Centre Hospitalier Universitaire de Brest - Hôpital Morvan
city: Grenoble Cedex 9
country: France
facility: Centre Hospitalier Universitaire de Grenoble - Hopital Nord Michallon
city: Montpellier cedex 5
country: France
facility: Hôpital Saint Eloi
city: Nice
country: France
facility: Centre Hospitalier Universitaire Archet 2
city: Pierre Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: Berlin
country: Germany
facility: *Charité*
city: Dresden
country: Germany
facility: Universitaetsklinikum Dresden
city: Mainz
country: Germany
facility: Johannes Gutenberg Universitaet Mainz
city: Athens
country: Greece
facility: Laiko General Hospital of Athens
city: Athens
country: Greece
facility: Sotiria General Hospital
city: Athens
country: Greece
facility: Attikon University General Hospital of Athens
city: Athens
country: Greece
facility: Andreas Syggros Hospital
city: Thessaloniki
country: Greece
facility: George Papageorgiou General Hospital of Thessaloniki
city: Milano
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria di Modena
city: Roma
country: Italy
facility: Fondazione Policlinico Tor Vergata
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Rozzano MI
country: Italy
facility: IRCCS Istituto Clinico Humanitas
city: Torino
country: Italy
facility: Azienda Ospedaliera Citta della Salute e della Scienza di Torino
city: Nagoya-shi
country: Japan
facility: Fujita Health University Bantane Hospital
state: Aichi
city: Hiroshima-shi
country: Japan
facility: Hiroshima University Hospital
state: Hiroshima
city: Obihiro-shi
country: Japan
facility: Takagi Dermatological Clinic
state: Hokkaido
city: Kawasaki-shi
country: Japan
facility: Kosugi Dermatology Clinic
state: Kanagawa
city: Yokohama-shi
country: Japan
facility: Nomura Dermatology Clinic
state: Kanagawa
city: Habikino-shi
country: Japan
facility: Osaka Habikino Medical Center
state: Osaka
city: Sakai-shi
country: Japan
facility: Dermatology and Ophthalmology Kume Clinic
state: Osaka
city: Itabashi-ku
country: Japan
facility: Nihon University Itabashi Hospital
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: NTT Medical Center Tokyo
state: Tokyo
city: Hwaseong-si, Gyeonggi-do
country: Korea, Republic of
facility: Hallym University Dongtan Sacred Heart Hospital
city: Seongnam-si, Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Hallym University Kangnam Sacred Heart Hospital
city: Suwon-si, Gyeonggi-do
country: Korea, Republic of
facility: Ajou University Hospital
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lodz
country: Poland
facility: AMICARE z ograniczona odpowiedzialnoscia spolka komandytowa
city: Lodz
country: Poland
facility: SPZOZ Centralny Szpital Kliniczny
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
city: Poznan
country: Poland
facility: Clinical Research Center Spzoo Medic-R Spolka Komandytowa
city: Rzeszow
country: Poland
facility: Kliniczny Szpital Wojewodzki nr 1 im Fryderyka Chopina
city: Warszawa
country: Poland
facility: Klinika Osipowicz and Turkowski Spzoo Opieka Wielospecjalistyczna Osipowicz and Turkowski
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny
city: Barcelona
country: Spain
facility: Hospital del Mar
state: Cataluña
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
state: Cataluña
city: Hospitalet de LLobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Cataluña
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Hospital Arnau de Vilanova de Valencia
state: Comunidad Valenciana
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: McLaren J, Chon Y, Gorski KS, Bernstein JA, Corren J, Hayama K, Jain V, Lima H, Sofen H, Ponnarambil S, Molfino NA, Maurer M. Tezepelumab for the treatment of chronic spontaneous urticaria: Results of the phase 2b INCEPTION study. J Allergy Clin Immunol. 2025 Feb 14:S0091-6749(25)00172-1. doi: 10.1016/j.jaci.2025.01.045. Online ahead of print.