Chronic Spontaneous Urticaria
Conditions
Interventions
Product Name: Tezepelumab
Pharmaceutical Form: Solution for injection
INN or Proposed INN: TEZEPELUMAB
CAS Number: 1572943-04-4
Current Sponsor code: AMG 157
Concentration unit: mg/ml milligram(s)/mil
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Subject has been informed about study procedures and medications and has provided informed consent prior to initiation of any study-specific activities/procedures • Subject is able to communicate with the investigator, and understands and complies with the requirements of the study • Age ? 18 to ? 80 years of age at screening • Chronic spontaneous urticaria diagnosis for ? 6 months at the time of screening visit 1 • Diagnosis of CSU inadequately controlled by 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 despite current use of an approved dose of H1- antihistamine -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 enrolment • 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 3consecutive days immediately prior to the day -14 screening visit (screening visit2) and must have documented current use on the day of screening visit 1 • This is not applicable for anti-IgE naïve subjects. Subject with CSU who discontinued, is intolerant to, or was an inadequate responder to anti-IgE therapies despite being treated with omalizumab 300 mg Q4W for 6 months or higher doses of omalizumab > 2 months (or per local country treatment standards) or another anti-IgE therapy. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 249 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 21
Exclusion criteria
Exclusion criteria: Disease Related: • 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 subject in the study, interfere with evaluation of the investigational product, or reduce the subject’s ability to participate in the study. Clinically significant infections are defined as either of the following: 1)a systemic infection; or 2) a serious skin infection requiring parenteral antibiotic, antiviral, or antifungal medication • Diagnosis of a helminth parasitic infection within 6 months prior to screening visit 1 that had not been treated with or had failed to respond to standard of care therapy • Documented medical history of chronic alcohol or drug abuse within 12 months prior to screening visit 1 • Evidence of active liver disease at screening, including jaundice or aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase greater than twice the upper limit of normal (ULN) • Subjects who, in the opinion of the investigator, have evidence of active tuberculosis (TB), either treated or untreated, or a positive purified protein derivative (PPD) or QuantiFERON-tuberculosis Gold Plus (QFT-Plus) test for TB during screening. Subjects with an indeterminate QFT-Plus may be enrolled if they have ALL of the following: o No symptoms of TB: productive, prolonged cough (> 3 weeks); coughing up blood; fever; night sweats; unexplained appetite loss; unintentional weight loss o No evidence of active TB on chest radiograph within 3 months prior to the first dose of investigational product. Note: Chest radiograph is not part of screening procedure and will be the responsibility of the Investigator as this is outside the scope of this protocol • 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 (? 80%) with the eDiary during the second phase of the screening period/ H1-antihistamine stabilization period o Completion of UAS (daily) for 14 days (?80% compliance) prior to randomization o Completion of AAS (daily) for 14 days (? 80% compliance) prior to randomization Other Medical Conditions • 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 must be reviewed and approved by the Medical Monitor • History or evidence of severe depression, schizophrenia, previous suicide attempts, or suicidal ideation Prior/Concomitant Thera
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of tezepelumab on improvement in the Urticaria Activity Score over 7 days (UAS7) ;Secondary Objective: •To evaluate the effect of tezepelumab on : •compared with placebo in CSU subjects using the UAS7 • improvement in itch using the Itch Severity Scoreover 7 days (ISS7) •improvement in hives using the Hives Severity Score over 7 days (HSS7) •subjects achieving minimal residual disease using the UAS7 •subjects achieving the minimal important difference (MID) on change from baseline in the UAS7 • on complete resolution of itch using the ISS7 •on subjects achieving the MID on change from baseline in the ISS7 •on the complete resolution of hives using the HSS7 •on subjects achieving the MID on change from baseline in the HSS7 • sleep interference and quality (falling asleep, nighttime awakenings, restfulness upon awakening) • improvement in urticaria disease control using the Urticaria Control Test (UCT) • angioedema using the Angioedema Activity Score over 7 days (AAS7) • the cumulative time period that treated subjects are angioedema occurrence-free using the AAS7 ;Primary end point(s): Change from baseline in UAS7 at week 16;Timepoint(s) of evaluation of this end point: week 16 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Complete response in UAS7 defined as UAS7 = 0 at week 16 • Change from baseline in ISS7 at week 16 • Change from baseline in HSS7 score at week 16 • UAS7 ? 6 at week 16 • Change from baseline in UAS7 ? 10 at week 16 • ISS7 = 0 at week 16 • Change from baseline in ISS7 ? 5 at week 16 • HSS7 = 0 at week 16 • Change from baseline in sleep interference score at week 16 • Change from baseline in the sleep interference and quality diary items at week 16 • Change from baseline UCT score at week 16 • Change from baseline in AAS7 at week 16 • Cumulative weeks that subjects achieve AAS7 = 0 responses between baseline and week 16 • Change from baseline in the CU-Q2oL at week 16 • Change from baseline in DLQI at week 16 • Change from baseline in the AE-QoL at week 16 • Change from baseline in the AECT score at week 16 • Change from baseline in WPAI-CU score at week 16 • Cumulative frequency of H1-antihistamine rescue medication utilization from baseline to week 16 • Serum concentrations of tezepelumab at scheduled visits • Subject incidence of adverse events (including serious adverse events) ;Timepoint(s) of evaluation of this end point: week 16 | — |
Countries
Canada, France, Germany, Greece, Italy, Japan, Korea, Republic of, Poland, Spain, United States
Contacts
Public ContactMedical Information
Amgen SAS
Outcome results
None listed