Study to Evaluate Tezepelumab in Adults With Chronic Spontaneous Urticaria (INCEPTION)

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

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

Study Overview

• Status: Completed
• Conditions: Chronic Spontaneous Urticaria
• Intervention / Treatment: Biological: Omalizumab; Biological: Placebo; Biological: Tezepelumab Dose 1; Biological: Tezepelumab Dose 2

• Study Type: Interventional
• Enrollment (Actual): 183
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4W2
    • Clinique Specialisee en Allergie de la Capitale
  • Alberta
    • Calgary, Alberta, Canada, T2J 7E1
      • Dermatology Research Institute Incorporated
  • New Brunswick
    • Fredericton, New Brunswick, Canada, E3B 1G9
      • Brunswick Dermatology Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8L 3C3
      • Leader Research
    • Markham, Ontario, Canada, L3P 1X3
      • Lynderm Research Inc
    • Mississauga, Ontario, Canada, L5A 3V4
      • Cheema Research Incorporated
    • Newmarket, Ontario, Canada, L3Y 5G8
      • Dr. S. K. Siddha Medicine Professional Corporation
    • Niagara Falls, Ontario, Canada, L2H 1H5
      • Allergy Research Canada Incorporated
    • North York, Ontario, Canada, M3B 3S6
      • Gordon Sussman Clinical Research Incorporated
• France
  • Brest, France, 29200
    • Centre Hospitalier Universitaire de Brest - Hôpital Morvan
  • Grenoble Cedex 9, France, 38043
    • Centre Hospitalier Universitaire de Grenoble - Hopital Nord Michallon
  • Montpellier cedex 5, France, 34295
    • Hopital Saint Eloi
  • Nice, France, 06202
    • Centre Hospitalier Universitaire Archet 2
  • Pierre Benite Cedex, France, 69495
    • Centre Hospitalier Lyon Sud
• Germany
  • Berlin, Germany, 12203
    • *Charité*
  • Dresden, Germany, 01307
    • Universitaetsklinikum Dresden
  • Mainz, Germany, 55101
    • Johannes Gutenberg Universitaet Mainz
• Greece
  • Athens, Greece, 11527
    • Sotiria General Hospital
  • Athens, Greece, 11527
    • Laiko General Hospital of Athens
  • Athens, Greece, 12462
    • Attikon University General Hospital of Athens
  • Athens, Greece, 16121
    • Andreas Syggros Hospital
  • Thessaloniki, Greece, 56403
    • George Papageorgiou General Hospital of Thessaloniki
• Italy
  • Milano, Italy, 20122
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
  • Modena, Italy, 41124
    • Azienda Ospedaliero Universitaria di Modena
  • Roma, Italy, 00168
    • Policlinico Universitario Agostino Gemelli
  • Roma, Italy, 00133
    • Fondazione Policlinico Tor Vergata
  • Rozzano MI, Italy, 20089
    • Irccs Istituto Clinico Humanitas
  • Torino, Italy, 10126
    • Azienda Ospedaliera Citta della Salute e della Scienza di Torino
• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan, 454-8509
      • Fujita Health University Bantane Hospital
  • Hiroshima
    • Hiroshima-shi, Hiroshima, Japan, 734-8551
      • Hiroshima University Hospital
  • Hokkaido
    • Obihiro-shi, Hokkaido, Japan, 080-0013
      • Takagi Dermatological Clinic
  • Kanagawa
    • Kawasaki-shi, Kanagawa, Japan, 211-0063
      • Kosugi Dermatology Clinic
    • Yokohama-shi, Kanagawa, Japan, 221-0825
      • Nomura Dermatology Clinic
  • Osaka
    • Habikino-shi, Osaka, Japan, 583-8588
      • Osaka Habikino Medical Center
    • Sakai-shi, Osaka, Japan, 593-8324
      • Dermatology and Ophthalmology Kume Clinic
  • Tokyo
    • Itabashi-ku, Tokyo, Japan, 173-8610
      • Nihon University Itabashi Hospital
    • Shinagawa-ku, Tokyo, Japan, 141-8625
      • NTT Medical Center Tokyo
• Korea, Republic of
  • Hwaseong-si, Gyeonggi-do, Korea, Republic of, 18450
    • Hallym University Dongtan Sacred Heart Hospital
  • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 07441
    • Hallym University Kangnam Sacred Heart Hospital
  • Suwon-si, Gyeonggi-do, Korea, Republic of, 16499
    • Ajou University Hospital
• Poland
  • Gdansk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne
  • Lodz, Poland, 91-495
    • AMICARE z ograniczona odpowiedzialnoscia spolka komandytowa
  • Lodz, Poland, 92-213
    • SPZOZ Centralny Szpital Kliniczny
  • Lublin, Poland, 20-081
    • Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
  • Poznan, Poland, 61-731
    • Clinical Research Center Spzoo Medic-R Spolka Komandytowa
  • Rzeszow, Poland, 35-055
    • Kliniczny Szpital Wojewodzki nr 1 im Fryderyka Chopina
  • Warszawa, Poland, 04-141
    • Wojskowy Instytut Medyczny
  • Warszawa, Poland, 02-473
    • Klinika Osipowicz and Turkowski Spzoo Opieka Wielospecjalistyczna Osipowicz and Turkowski
• Spain
  • Cataluña
    • Barcelona, Cataluña, Spain, 08003
      • Hospital Del Mar
    • Barcelona, Cataluña, Spain, 08041
      • Hospital de la Santa Creu i Sant Pau
    • Hospitalet de LLobregat, Cataluña, Spain, 08907
      • Hospital Universitari de Bellvitge
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46014
      • Hospital General Universitario de Valencia
    • Valencia, Comunidad Valenciana, Spain, 46015
      • Hospital Arnau de Vilanova de Valencia
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Clinical Research Center of Alabama
  • California
    • Fountain Valley, California, United States, 92708
      • First OC Dermatology
    • Laguna Niguel, California, United States, 92677
      • Avance Clinical Trials
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associates
    • Los Angeles, California, United States, 90025
      • Jonathan Corren MD Inc
    • Santa Monica, California, United States, 90404
      • Clinical Science Institute
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Asthma and Allergy Associates PC
  • Florida
    • Miami Lakes, Florida, United States, 33016
      • The Community Research of South Florida
  • Georgia
    • Sandy Springs, Georgia, United States, 30328
      • Advanced Medical Research Pc
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Dawes Fretzin Clinical Research Group, LLC
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Epiphany Dermatology of Kansas, LLC
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Bluegrass Allergy Care
    • Louisville, Kentucky, United States, 40215
      • Family Allergy and Asthma Research Institute
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Asthma and Allergy Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48103
      • David Fivenson MD Professional Liability Company
    • Clarkston, Michigan, United States, 48346
      • Clarkston Skin Research
    • Detroit, Michigan, United States, 48202
      • Henry Ford Medical Center - New Center One
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Bernstein Clinical Research Center LLC
    • Dublin, Ohio, United States, 43016
      • Aventiv Research Inc
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
      • Clinical Partners LLC
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • The Allergy Asthma and Sinus Center, East Tennessee Center for Clinical Research
  • Texas
    • Houston, Texas, United States, 77056
      • Suzanne Bruce and Associates
    • Laredo, Texas, United States, 78041
      • Cutis Wellness Dermatology and Dermatopathology, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1: Omalizumab; Participants naive to anti-IgE therapies will receive omalizumab.	Biological: Omalizumab; Subcutaneous injection.; Other Names: Xolair
Placebo Comparator: Group 2: Placebo; Participants naive to anti-IgE therapies will receive a placebo.	Biological: Placebo; Subcutaneous injection.
Experimental: Group 3: Tezepelumab Dose 1; Participants naive to anti-IgE therapies will receive tezepelumab.	Biological: Tezepelumab Dose 1; Subcutaneous injection.; Other Names: AMG 157
Experimental: Group 4: Tezepelumab Dose 2; Participants naive to anti-IgE therapies will receive tezepelumab.	Biological: Tezepelumab Dose 2; Subcutaneous injection.; Other Names: AMG 157
Placebo Comparator: Group 5: Placebo; Participants previously treated with anti-IgE therapies will receive a placebo.	Biological: Placebo; Subcutaneous injection.
Experimental: Group 6: Tezepelumab Dose 1; Participants previously treated with anti-IgE therapies will receive tezepelumab.	Biological: Tezepelumab Dose 1; Subcutaneous injection.; Other Names: AMG 157
Experimental: Group 7: Tezepelumab Dose 2; Participants previously treated with anti-IgE therapies will receive tezepelumab.	Biological: Tezepelumab Dose 2; Subcutaneous injection.; Other Names: AMG 157

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in Urticaria Activity Score over 7 days (UAS7)	Baseline to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with a Complete Response in Urticaria Activity Score over 7 Days (UAS7)	Complete response is defined as having a UAS7 score of 0 at week 16.	Week 16
Change from Baseline in Itch Severity Score over 7 Days (ISS7)		Baseline to Week 16
Change from Baseline in Hives Severity Score over 7 Days (HSS7)		Baseline to Week 16
Number of Participants with a Urticaria Activity Score over 7 days (UAS7) Score of 6 or Below		Week 16
Number of Participants with a Change from Baseline in Urticaria Activity Score over 7 days (UAS7) of ≤ -10		Baseline to Week 16
Number of Participants with a Complete Resolution of Itch using the Itch Severity Score over 7 Days (ISS7)	Complete resolution of itch is defined as having a ISS7 score of 0 at week 16.	Week 16
Number of Participants with a Change from Baseline in Itch Severity Score over 7 days (ISS7) of ≤ -5		Baseline to Week 16
Number of Participants with a Complete Resolution of Hives using the Hives Severity Score over 7 Days (HSS7)	Complete resolution of hives is defined as a HSS7 score of 0 at week 16.	Week 16
Number of Participants with a Change from Baseline in Hives Severity Score over 7 Days (HSS7) of ≤ -5.5		Baseline to Week 16
Change from Baseline in Sleep Interference Score		Baseline to Week 16
Change from Baseline in Sleep Quality Diary Items		Baseline to Week 16
Change from Baseline in Urticaria Control Test (UCT) Score		Baseline to Week 16
Change from Baseline in Angioedema Activity Score over 7 Days (AAS7)		Baseline to Week 16
Number of Cumulative Weeks that Participants are Angioedema Occurrence-free using the Angioedema Activity Score over 7 Days (AAS7)		Baseline to Week 16
Change from Baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Score		Baseline to Week 16
Change from Baseline in Dermatology Life Quality Index (DLQI) Score		Baseline to Week 16
Change from Baseline in Angioedema Quality of Life Questionnaire (AE-QoL) Score		Baseline to Week 16
Change from Baseline in Angioedema Control Test (AECT) Score		Baseline to Week 16
Number of Participants with Complete Control in Angioedema Control Test (AECT)	Complete control is defined as having an AECT score of 16 at week 16.	Week 16
Change from Baseline in Work Productivity and Activity Impairment Questionnaire: Chronic Urticaria (WPAI-CU) Score		Baseline to Week 16
Total Number of H1-antihistamine Rescue Medication Uses		Baseline to Week 16
Maximum Observed Concentration of Tezepelumab in Serum (Cmax)		Baseline to Week 16
Number of Participants who Experience an Adverse Event (AE)		Baseline to Week 32
Number of Participants who Experience a Serious Adverse Event (SAE)		Baseline to Week 32

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2021
• Primary Completion (Actual): December 20, 2022
• Study Completion (Actual): April 13, 2023

Study Registration Dates

• First Submitted: April 5, 2021
• First Submitted That Met QC Criteria: April 5, 2021
• First Posted (Actual): April 6, 2021

Study Record Updates

• Last Update Posted (Actual): September 14, 2023
• Last Update Submitted That Met QC Criteria: September 8, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: CSU
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Disease Attributes; Skin Diseases, Vascular; Hypersensitivity; Chronic Disease; Urticaria; Chronic Urticaria; Physiological Effects of Drugs; Immunologic Factors; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Antibodies, Monoclonal; Omalizumab
• Other Study ID Numbers: 20190194

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No