Atopic Dermatitis
Conditions
Keywords
Atopic Dermatitis, eczema, tezepelumab, dermatology, dermatitis, inflammation, skin, moderate dermatitis, severe dermatitis
Brief summary
This phase 2b study is designed to evaluate the safety and efficacy of tezepelumab as a monotherapy and explore its efficacy as adjunct therapy in subjects with moderate-to-severe atopic dermatitis (AD).
Detailed description
All subjects will receive a subcutaneous (SC) dose of either investigational product or placebo as the first dose on day 1. Subjects who are determined to be non-responders in Part A will receive tezepelumab SC every 2 weeks (Q2W) following completion of all week 16 study activities. Nonresponders are defined as those subjects who have not achieved at least a 50% improvement in Eczema Area and Severity Index (EASI) at week 16 compared to baseline (day 1). Safety follow-up is 18 weeks after the end of treatment (EOT) visit (20 weeks after the final dose of investigational product).
Interventions
DRUGTezepelumab
Solution for injection
OTHERPlacebo
Placebo solution for injection
Sponsors
AstraZeneca
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This phase 2b study is designed to evaluate the safety and efficacy of tezepelumab as a monotherapy and explore its efficacy as adjunct therapy in subjects with moderate-to-severe AD. This study consists of Part A (the main study evaluating tezepelumab as a monotherapy) and Part B (a study evaluating tezepelumab as adjunctive therapy when combined with a topical corticosteroid regimen
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subject has provided informed consent prior to initiation of any study specific activities/procedures. * Age greater than or equal to 18 to less than or equal to 75 years at screening. * Clinical diagnosis of chronic AD (also known as atopic eczema) for at least 2 years prior to screening and has confirmed AD (Hanifin and Rajka criteria for AD (Hanifin and Rajka, 1980). * AD that affects greater than or equal to' 10% body surface area as assessed by EASI at screening and on day 1. * An IGA score of greater than or equal to 3 at screening and on day 1. * An EASI score of greater than or equal to 16 at screening and on day 1. * Subject discontinued treatment with TCS, topical calcineurin inhibitors (TCI), and prescription moisturizers containing TCS or topical calcineurin inhibitors (TCI) for at least the 7 days immediately prior to the first dose of investigational product * Documented recent history (within 12 months before the screening visit) of inadequate response totreatment with topical TCS or subjects for whom topical treatments are otherwise medically inadvisable (ie, because of important side effects or safety risks). * Inadequate response is defined as failure to achieve and maintain remission or a low disease activity state (comparable to IGA 0 = clear to IGA 2 = mild) despite treatment with a daily regimen of TCS of medium or higher potency (with or without TCI as appropriate).
Exclusion criteria
* Active dermatologic conditions, which might confound the diagnosis of AD or would interfere with the assessment of treatment, such as scabies, seborrheic dermatitis, cutaneous lymphoma, ichthyosis, psoriasis, allergic contact dermatitis, or irritant contact dermatitis. * 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 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. * History of anaphylaxis following any biologic therapy. * 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 QuantiFERON-tuberculosis Gold (QFT-G) test for TB during screening. Subjects with an indeterminate QFT-G may be enrolled if they have ALL of the following: * No symptoms of TB: productive, prolonged cough (\> 3 weeks); coughing up blood; fever; night sweats; unexplained appetite loss; unintentional weight loss * 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 * Positive hepatitis B surface antigen or hepatitis C antibody serology. Subjects with a history of hepatitis B vaccination without a history of hepatitis B are allowed to enroll in the study. * Positive human immunodeficiency virus (HIV) test at screening or the subject is taking antiretroviral medications, as determined by medical history, prior medications, and/or the subject's verbal report. * Other Medical Conditions\> * 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. * History or evidence of severe depression, schizophrenia, previous suicide attempts, or suicidal ideation. Prior/Concomitant Therapy: * Subjects who are unwilling to abstain from the use of TCS, TCI, and prescription moisturizers (those that contain TCS and TCI) from screening through week 16 (applies only to Part A subjects) * Subjects who have had side effects of topical medications including intolerance to treatment, hypersensitivity reactions, significant skin atrophy, or systemic effects as assessed by the investigator or by the subject's treating physician (applies only to Part B subjects) * More than or equal to 30% of the total lesional surface is located on areas of thin skin that cannot be safely treated with medium or higher potency TCS (eg, face, neck, intertriginous areas, areas of skin atrophy) (applies only to Part B subjects) * Receipt of any approved biologic agent (eg, dupilumab) within 4 months or 5 elimination half-lives (whichever is longer) prior to screening * Have used immunosuppressive/immunomodulating drugs (eg, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, interferon (IFN)-gamma, Janus kinase inhibitors, azathioprine, methotrexate) within 4 weeks prior to screening, or any condition that, in the opinion of the investigator, is likely to require such treatment(s) during the first 4 weeks of study treatment. * Have had phototherapy for AD in the 2 months prior to day 1, and subjects unwilling to avoid phototherapy during the first 16 weeks of the study * If on allergen-specific immunotherapy, subjects must be on a maintenance dose and schedule for ≥ 28 days prior to screening. Allergen-specific immunotherapy is defined as SC immunotherapy to aeroallergens and/o venom (Hymenoptera) as well as sublingual immunotherapy to aeroallergens * Vaccination with a live or attenuated vaccine within 28 days prior to day 1. Receipt of inactive/killed vaccinations (eg, inactive influenza) is allowed. Note that receipt of the Th2 cytokine inhibitor suplatast within 15 days prior to randomization and during the study is not allowed. * Major surgery within 8 weeks prior to screening or planned inpatient surgery or hospitalization during the study period * Currently receiving treatment in another investigational device or drug study, or less than 6 months since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded. Other Exclusions: * Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 16 weeks after the last dose of investigational product. (Females of childbearing potential should only be enrolled in the study after a negative highly sensitive serum pregnancy test). * Female subjects of childbearing potential who are sexually active with unsterilized male partners unwilling to use 1 highly effective method of contraception during treatment and for an additional 16 weeks after the last dose of investigational product. Cessation of contraception after this point must be discussed with a responsible physician. Females of childbearing potential are defined as those who are not surgically sterile (ie, had bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause). A highly effective method of contraception is defined as one that resulted in a low failure rate (ie, \< 1% per year) when used consistently and correctly. * Subject has known sensitivity to any of the products or components to be administered during dosing. * History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) (IGA 0/1) at Week 16 | Week 16 | The IGA allows investigators to assess overall disease severity at 1 given time point and consists of a 6-point severity scale from clear to severe disease * 0 = clear * 1 = almost clear * 2 = mild disease * 3 = moderate disease * 4 = severe disease * 5 = very severe disease The IGA uses clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines for the overall severity assessment (Breuer et al, 2004). Participants who took rescue medication between Day 29 to Week 16 were considered non-responders. |
| Number of Participants Who Experienced a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) at Week 16 | Baseline and Week 16 | The EASI evaluates 4 natural anatomical regions for severity and extent of key disease signs and focuses on key acute and chronic signs of inflammation (ie, erythema, induration/papulation, excoriation, and lichenification). A reduction in the EASI score indicates an improvement in severity. Participants who took rescue medication between Day 29 to Week 16 were considered non-responders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced a 50% or 90% Reduction From Baseline in Eczema Area and Severity Index (EASI 50/90) at Week 16 | Baseline and Week 16 | The EASI evaluates 4 natural anatomical regions for severity and extent of key disease signs and focuses on key acute and chronic signs of inflammation (ie, erythema, induration/papulation, excoriation, and lichenification). A reduction in the EASI score indicates an improvement in severity. Participants who took rescue medication between Day 29 to Week 16 were considered non-responders. |
| Time to Achievement of 50%, 75% or 90% Reduction From Day 1 in Eczema Area and Severity Index (EASI 50/75/90) | Day 1 up to End of Study Visit (Week 70) | — |
| Change From Baseline in Scoring of Atopic Dermatitis (SCORAD) at Week 16 | Baseline and Week 16 | The SCORAD is a clinical tool for assessing the severity (ie, extent, intensity) of atopic dermatitis (AD). The tool evaluates the extent and intensity of the AD lesions, along with subjective symptoms (Kunz et al, 1997). The total score ranges from 0 to 103, with higher values indicating more severe disease. A negative change from baseline indicates an improvement in severity of disease. |
| Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16 | Baseline and Week 16 | Pruritus was assessed using an NRS (0-10) with 0 = no itch and 10 = worst imaginable itch. A negative change from baseline indicates an improvement in symptoms. |
| Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Pre-dose on Day 1, Week 2, 4, 12, 16, 24, 32, 40, 48, 50, 52, 58 and 70 | Switchers were included up to Week 16 and were then excluded from the analysis after switching. All Tezepelumab participants received 420 mg of Tezepelumab on Day 1. |
| Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Pre-dose on Week 24, 32, 40, 48, 50, 52, 58 and 70 | — |
Countries
Australia, Canada, Czechia, Estonia, Germany, Hungary, Japan, Latvia, Poland, South Korea, Spain, Switzerland, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled in 78 centers in 14 countries including Australia, Canada, Czech Republic, Estonia, Germany, Hungary, Japan, Latvia, Poland, Republic of Korea, Spain, Ukraine, the United Kingdom, and the United States.
Pre-assignment details
Enrollment of Part A of this study was completed as of 27 July 2020. The study was terminated prior to the enrollment of any participants into Part B.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Placebo Matching placebo administered via subcutaneous (SC) injection once every 2 weeks (Q2W) for a maximum of 52 weeks.
Participants defined as non-responders (those who did not achieve at least 50% improvement in Eczema Area and Severity Index \[EASI\] compared to baseline) at Week 16 switched to receive tezepelumab 420 mg SC injection Q2W for the remainder of the study. | 63 |
| Part A: Tezepelumab 210 mg Q4W Tezepelumab 210 mg administered via SC injection once every 4 weeks (Q4W) from Week 4 for a maximum of 52 weeks.
All participants randomized to tezepelumab received 420 mg SC injection as their first dose. Participants then received a placebo at Week 2 and every other week to maintain blinding.
Participants defined as non-responders (those who did not achieve at least 50% improvement in EASI compared to baseline) at Week 16 switched to receive tezepelumab 420 mg SC injection Q2W for the remainder of the study. | 62 |
| Part A: Tezepelumab 280 mg Q2W Tezepelumab 280 mg administered via SC injection Q2W from Week 2 for a maximum of 52 weeks.
All participants randomized to tezepelumab received 420 mg SC injection as their first dose. Participants then received their randomized dose of 280 mg Q2W from Week 2.
Participants defined as non-responders (those who did not achieve at least 50% improvement in EASI compared to baseline) at Week 16 switched to receive tezepelumab 420 mg SC injection Q2W for the remainder of the study. | 63 |
| Part A: Tezepelumab 420 mg Q2W Tezepelumab 420 mg administered via SC injection Q2W for a maximum of 52 weeks.
Participants defined as non-responders (those who did not achieve at least 50% improvement in EASI compared to baseline) at Week 16 stayed to receive tezepelumab 420 mg SC injection Q2W for the remainder of the study. | 63 |
| Total | 251 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Decision by sponsor | 24 | 18 | 20 | 20 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 4 | 1 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 26 | 22 | 27 | 26 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A: Placebo | Part A: Tezepelumab 210 mg Q4W | Part A: Tezepelumab 280 mg Q2W | Part A: Tezepelumab 420 mg Q2W | Total |
|---|---|---|---|---|---|
| Age, Continuous | 35.7 Years STANDARD_DEVIATION 13.4 | 38.5 Years STANDARD_DEVIATION 15 | 36.9 Years STANDARD_DEVIATION 13.4 | 40.7 Years STANDARD_DEVIATION 14.3 | 37.9 Years STANDARD_DEVIATION 14.1 |
| Eczema Area and Severity Index (EASI) | 32.0 Score on a scale STANDARD_DEVIATION 11.1 | 28.4 Score on a scale STANDARD_DEVIATION 13.2 | 30.3 Score on a scale STANDARD_DEVIATION 10.7 | 28.6 Score on a scale STANDARD_DEVIATION 12.4 | 29.8 Score on a scale STANDARD_DEVIATION 11.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 4 Participants | 1 Participants | 4 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants | 58 Participants | 62 Participants | 59 Participants | 236 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Investigator's Global Assessment Score IGA Score of 3 | 26 Participants | 37 Participants | 26 Participants | 37 Participants | 126 Participants |
| Investigator's Global Assessment Score IGA Score of 4 | 32 Participants | 17 Participants | 30 Participants | 18 Participants | 97 Participants |
| Investigator's Global Assessment Score IGA Score of 5 | 5 Participants | 8 Participants | 7 Participants | 8 Participants | 28 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 21 Participants | 16 Participants | 16 Participants | 13 Participants | 66 Participants |
| Race/Ethnicity, Customized Black or African-American | 1 Participants | 3 Participants | 1 Participants | 3 Participants | 8 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 41 Participants | 42 Participants | 45 Participants | 47 Participants | 175 Participants |
| Sex: Female, Male Female | 27 Participants | 32 Participants | 23 Participants | 27 Participants | 109 Participants |
| Sex: Female, Male Male | 36 Participants | 30 Participants | 40 Participants | 36 Participants | 142 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 63 | 0 / 59 | 0 / 58 | 0 / 70 | 0 / 12 | 0 / 25 | 0 / 20 | 0 / 22 | 0 / 39 | 0 / 24 | 0 / 30 | 0 / 38 |
| other Total, other adverse events | 25 / 63 | 20 / 59 | 29 / 58 | 30 / 70 | 6 / 12 | 10 / 25 | 11 / 20 | 5 / 22 | 18 / 39 | 9 / 24 | 10 / 30 | 19 / 38 |
| serious Total, serious adverse events | 0 / 63 | 2 / 59 | 0 / 58 | 1 / 70 | 0 / 12 | 0 / 25 | 1 / 20 | 0 / 22 | 2 / 39 | 0 / 24 | 1 / 30 | 4 / 38 |
Outcome results
Primary
Number of Participants Who Experienced a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) at Week 16
The EASI evaluates 4 natural anatomical regions for severity and extent of key disease signs and focuses on key acute and chronic signs of inflammation (ie, erythema, induration/papulation, excoriation, and lichenification). A reduction in the EASI score indicates an improvement in severity. Participants who took rescue medication between Day 29 to Week 16 were considered non-responders.
Time frame: Baseline and Week 16
Population: FAS: All randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Placebo | Number of Participants Who Experienced a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) at Week 16 | 8 Participants |
| Part A: Tezepelumab 210 mg Q4W | Number of Participants Who Experienced a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) at Week 16 | 9 Participants |
| Part A: Tezepelumab 280 mg Q2W | Number of Participants Who Experienced a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) at Week 16 | 10 Participants |
| Part A: Tezepelumab 420 mg Q2W | Number of Participants Who Experienced a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) at Week 16 | 7 Participants |
p-value: 0.9795% CI: [0.344, 2.803]Regression, Logistic
p-value: 0.795% CI: [0.441, 3.356]Regression, Logistic
p-value: 0.5895% CI: [0.243, 2.197]Regression, Logistic
Primary
Number of Participants With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) (IGA 0/1) at Week 16
The IGA allows investigators to assess overall disease severity at 1 given time point and consists of a 6-point severity scale from clear to severe disease * 0 = clear * 1 = almost clear * 2 = mild disease * 3 = moderate disease * 4 = severe disease * 5 = very severe disease The IGA uses clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines for the overall severity assessment (Breuer et al, 2004). Participants who took rescue medication between Day 29 to Week 16 were considered non-responders.
Time frame: Week 16
Population: FAS: All randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Placebo | Number of Participants With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) (IGA 0/1) at Week 16 | 2 Participants |
| Part A: Tezepelumab 210 mg Q4W | Number of Participants With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) (IGA 0/1) at Week 16 | 4 Participants |
| Part A: Tezepelumab 280 mg Q2W | Number of Participants With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) (IGA 0/1) at Week 16 | 2 Participants |
| Part A: Tezepelumab 420 mg Q2W | Number of Participants With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) (IGA 0/1) at Week 16 | 5 Participants |
p-value: 0.5695% CI: [0.29, 9.809]Regression, Logistic
p-value: 0.9995% CI: [0.135, 7.551]Regression, Logistic
p-value: 0.3895% CI: [0.39, 11.8]Regression, Logistic
Secondary
Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16
Pruritus was assessed using an NRS (0-10) with 0 = no itch and 10 = worst imaginable itch. A negative change from baseline indicates an improvement in symptoms.
Time frame: Baseline and Week 16
Population: FAS: All randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16 | -0.71 Score on a scale | Standard Error 0.3 |
| Part A: Tezepelumab 210 mg Q4W | Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16 | -1.40 Score on a scale | Standard Error 0.27 |
| Part A: Tezepelumab 280 mg Q2W | Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16 | -0.94 Score on a scale | Standard Error 0.28 |
| Part A: Tezepelumab 420 mg Q2W | Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16 | -0.38 Score on a scale | Standard Error 0.28 |
Secondary
Change From Baseline in Scoring of Atopic Dermatitis (SCORAD) at Week 16
The SCORAD is a clinical tool for assessing the severity (ie, extent, intensity) of atopic dermatitis (AD). The tool evaluates the extent and intensity of the AD lesions, along with subjective symptoms (Kunz et al, 1997). The total score ranges from 0 to 103, with higher values indicating more severe disease. A negative change from baseline indicates an improvement in severity of disease.
Time frame: Baseline and Week 16
Population: FAS: All randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Change From Baseline in Scoring of Atopic Dermatitis (SCORAD) at Week 16 | -8.00 Score on a scale | Standard Error 2.55 |
| Part A: Tezepelumab 210 mg Q4W | Change From Baseline in Scoring of Atopic Dermatitis (SCORAD) at Week 16 | -16.75 Score on a scale | Standard Error 2.4 |
| Part A: Tezepelumab 280 mg Q2W | Change From Baseline in Scoring of Atopic Dermatitis (SCORAD) at Week 16 | -11.87 Score on a scale | Standard Error 2.49 |
| Part A: Tezepelumab 420 mg Q2W | Change From Baseline in Scoring of Atopic Dermatitis (SCORAD) at Week 16 | -9.32 Score on a scale | Standard Error 2.48 |
Secondary
Number of Participants Who Experienced a 50% or 90% Reduction From Baseline in Eczema Area and Severity Index (EASI 50/90) at Week 16
The EASI evaluates 4 natural anatomical regions for severity and extent of key disease signs and focuses on key acute and chronic signs of inflammation (ie, erythema, induration/papulation, excoriation, and lichenification). A reduction in the EASI score indicates an improvement in severity. Participants who took rescue medication between Day 29 to Week 16 were considered non-responders.
Time frame: Baseline and Week 16
Population: FAS: All randomized participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Placebo | Number of Participants Who Experienced a 50% or 90% Reduction From Baseline in Eczema Area and Severity Index (EASI 50/90) at Week 16 | EASI 50 | 11 Participants |
| Part A: Placebo | Number of Participants Who Experienced a 50% or 90% Reduction From Baseline in Eczema Area and Severity Index (EASI 50/90) at Week 16 | EASI 90 | 3 Participants |
| Part A: Tezepelumab 210 mg Q4W | Number of Participants Who Experienced a 50% or 90% Reduction From Baseline in Eczema Area and Severity Index (EASI 50/90) at Week 16 | EASI 90 | 3 Participants |
| Part A: Tezepelumab 210 mg Q4W | Number of Participants Who Experienced a 50% or 90% Reduction From Baseline in Eczema Area and Severity Index (EASI 50/90) at Week 16 | EASI 50 | 21 Participants |
| Part A: Tezepelumab 280 mg Q2W | Number of Participants Who Experienced a 50% or 90% Reduction From Baseline in Eczema Area and Severity Index (EASI 50/90) at Week 16 | EASI 50 | 18 Participants |
| Part A: Tezepelumab 280 mg Q2W | Number of Participants Who Experienced a 50% or 90% Reduction From Baseline in Eczema Area and Severity Index (EASI 50/90) at Week 16 | EASI 90 | 3 Participants |
| Part A: Tezepelumab 420 mg Q2W | Number of Participants Who Experienced a 50% or 90% Reduction From Baseline in Eczema Area and Severity Index (EASI 50/90) at Week 16 | EASI 50 | 11 Participants |
| Part A: Tezepelumab 420 mg Q2W | Number of Participants Who Experienced a 50% or 90% Reduction From Baseline in Eczema Area and Severity Index (EASI 50/90) at Week 16 | EASI 90 | 3 Participants |
Secondary
Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration
Switchers were included up to Week 16 and were then excluded from the analysis after switching. All Tezepelumab participants received 420 mg of Tezepelumab on Day 1.
Time frame: Pre-dose on Day 1, Week 2, 4, 12, 16, 24, 32, 40, 48, 50, 52, 58 and 70
Population: All randomized participants who received at least 1 dose of investigational product with analyzable samples at each time point. Participants were analyzed according to the highest dose of actual treatment received after initial first dose or only dose received. Switchers were included up to Week 16 and were then excluded from the analysis after switching at Week 16.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 58 | 5.41 µg/mL | Standard Deviation 2.56 |
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 48 | 18.2 µg/mL | Standard Deviation 6.49 |
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 24 | 23.2 µg/mL | Standard Deviation 10.6 |
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 4 | 23.4 µg/mL | Standard Deviation 9.03 |
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 40 | 22.9 µg/mL | Standard Deviation 12.7 |
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 32 | 25.4 µg/mL | Standard Deviation 17 |
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Day 1 | 0.00031 µg/mL | Standard Deviation 0.00236 |
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 2 | 34.9 µg/mL | Standard Deviation 10.9 |
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 52 | 18.3 µg/mL | Standard Deviation 7.24 |
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 12 | 21.7 µg/mL | Standard Deviation 8.47 |
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 70 | 0.699 µg/mL | Standard Deviation 0.38 |
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 50 | 29.2 µg/mL | Standard Deviation 9.11 |
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 16 | 22.2 µg/mL | Standard Deviation 9.42 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 32 | 75.1 µg/mL | Standard Deviation 36.3 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Day 1 | 0.00 µg/mL | Standard Deviation 0 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 2 | 36.3 µg/mL | Standard Deviation 12.9 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 4 | 48.8 µg/mL | Standard Deviation 16 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 12 | 66.7 µg/mL | Standard Deviation 22.9 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 16 | 77.4 µg/mL | Standard Deviation 33 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 24 | 83.6 µg/mL | Standard Deviation 31.2 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 40 | 76.8 µg/mL | Standard Deviation 19.7 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 48 | 76.4 µg/mL | Standard Deviation 26.4 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 50 | 86.8 µg/mL | Standard Deviation 27.7 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 52 | 67.2 µg/mL | Standard Deviation 33.2 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 58 | 18.0 µg/mL | Standard Deviation 7.09 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 70 | 1.87 µg/mL | Standard Deviation 1.74 |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 48 | 118 µg/mL | Standard Deviation 48.3 |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 12 | 97.0 µg/mL | Standard Deviation 35 |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 58 | 20.9 µg/mL | — |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 50 | 113 µg/mL | Standard Deviation 44.4 |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 4 | 58.9 µg/mL | Standard Deviation 21.4 |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Day 1 | 0.00 µg/mL | Standard Deviation 0 |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 52 | 102 µg/mL | Standard Deviation 31.2 |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 32 | 81.4 µg/mL | Standard Deviation 26.4 |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 24 | 107 µg/mL | Standard Deviation 29.5 |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 2 | 34.8 µg/mL | Standard Deviation 12.9 |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 40 | 112 µg/mL | Standard Deviation 63.3 |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 16 | 98.0 µg/mL | Standard Deviation 37.8 |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration | Week 70 | 5.36 µg/mL | Standard Deviation 3.2 |
Secondary
Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16
Time frame: Pre-dose on Week 24, 32, 40, 48, 50, 52, 58 and 70
Population: All randomized participants who received at least 1 dose of investigational product who were assessed as EASI non-responders at Week 16 and switched to 420 mg Q2W, with analyzable samples at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 24 | 70.5 µg/mL | Standard Deviation 28.3 |
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 32 | 91.0 µg/mL | Standard Deviation 38.7 |
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 40 | 117 µg/mL | Standard Deviation 42.7 |
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 48 | 134 µg/mL | Standard Deviation 60.2 |
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 50 | 115 µg/mL | Standard Deviation 39 |
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 52 | 125 µg/mL | Standard Deviation 30.8 |
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 58 | 26.0 µg/mL | Standard Deviation 21.6 |
| Part A: Placebo | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 70 | 5.07 µg/mL | Standard Deviation 5.1 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 52 | 113 µg/mL | Standard Deviation 45 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 50 | 125 µg/mL | Standard Deviation 42.2 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 32 | 104 µg/mL | Standard Deviation 38.8 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 70 | 4.47 µg/mL | Standard Deviation 3.39 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 58 | 52.6 µg/mL | — |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 48 | 121 µg/mL | Standard Deviation 29.1 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 40 | 93.8 µg/mL | Standard Deviation 35.5 |
| Part A: Tezepelumab 210 mg Q4W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 24 | 87.2 µg/mL | Standard Deviation 24 |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 58 | 36.7 µg/mL | — |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 40 | 113 µg/mL | Standard Deviation 31.1 |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 48 | 89.6 µg/mL | Standard Deviation 35.1 |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 50 | 79.1 µg/mL | Standard Deviation 38.6 |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 52 | 88.3 µg/mL | Standard Deviation 33 |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 70 | 2.60 µg/mL | Standard Deviation 1.72 |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 24 | 96.6 µg/mL | Standard Deviation 29.2 |
| Part A: Tezepelumab 280 mg Q2W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 32 | 97.8 µg/mL | Standard Deviation 39.3 |
| Part A: Tezepelumab 420 mg Q2W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 40 | 101 µg/mL | Standard Deviation 37.7 |
| Part A: Tezepelumab 420 mg Q2W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 48 | 103 µg/mL | Standard Deviation 29.9 |
| Part A: Tezepelumab 420 mg Q2W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 32 | 105 µg/mL | Standard Deviation 39.1 |
| Part A: Tezepelumab 420 mg Q2W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 24 | 100 µg/mL | Standard Deviation 38.2 |
| Part A: Tezepelumab 420 mg Q2W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 50 | 106 µg/mL | Standard Deviation 27 |
| Part A: Tezepelumab 420 mg Q2W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 70 | 3.49 µg/mL | Standard Deviation 2.42 |
| Part A: Tezepelumab 420 mg Q2W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 58 | 17.6 µg/mL | Standard Deviation 9.28 |
| Part A: Tezepelumab 420 mg Q2W | Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 | Week 52 | 105 µg/mL | Standard Deviation 30.2 |
Secondary
Time to Achievement of 50%, 75% or 90% Reduction From Day 1 in Eczema Area and Severity Index (EASI 50/75/90)
Time frame: Day 1 up to End of Study Visit (Week 70)
Population: FAS: All randomized participants.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Placebo | Time to Achievement of 50%, 75% or 90% Reduction From Day 1 in Eczema Area and Severity Index (EASI 50/75/90) | Time to EASI 50 | 6.143 Weeks |
| Part A: Placebo | Time to Achievement of 50%, 75% or 90% Reduction From Day 1 in Eczema Area and Severity Index (EASI 50/75/90) | Time to EASI 90 | 8.286 Weeks |
| Part A: Placebo | Time to Achievement of 50%, 75% or 90% Reduction From Day 1 in Eczema Area and Severity Index (EASI 50/75/90) | Time to EASI 75 | 6.143 Weeks |
| Part A: Tezepelumab 210 mg Q4W | Time to Achievement of 50%, 75% or 90% Reduction From Day 1 in Eczema Area and Severity Index (EASI 50/75/90) | Time to EASI 50 | 8.143 Weeks |
| Part A: Tezepelumab 210 mg Q4W | Time to Achievement of 50%, 75% or 90% Reduction From Day 1 in Eczema Area and Severity Index (EASI 50/75/90) | Time to EASI 90 | 10.929 Weeks |
| Part A: Tezepelumab 210 mg Q4W | Time to Achievement of 50%, 75% or 90% Reduction From Day 1 in Eczema Area and Severity Index (EASI 50/75/90) | Time to EASI 75 | 6.286 Weeks |
| Part A: Tezepelumab 280 mg Q2W | Time to Achievement of 50%, 75% or 90% Reduction From Day 1 in Eczema Area and Severity Index (EASI 50/75/90) | Time to EASI 75 | 6.714 Weeks |
| Part A: Tezepelumab 280 mg Q2W | Time to Achievement of 50%, 75% or 90% Reduction From Day 1 in Eczema Area and Severity Index (EASI 50/75/90) | Time to EASI 50 | 6.286 Weeks |
| Part A: Tezepelumab 280 mg Q2W | Time to Achievement of 50%, 75% or 90% Reduction From Day 1 in Eczema Area and Severity Index (EASI 50/75/90) | Time to EASI 90 | 10.071 Weeks |
| Part A: Tezepelumab 420 mg Q2W | Time to Achievement of 50%, 75% or 90% Reduction From Day 1 in Eczema Area and Severity Index (EASI 50/75/90) | Time to EASI 50 | 5.857 Weeks |
| Part A: Tezepelumab 420 mg Q2W | Time to Achievement of 50%, 75% or 90% Reduction From Day 1 in Eczema Area and Severity Index (EASI 50/75/90) | Time to EASI 90 | 7.286 Weeks |
| Part A: Tezepelumab 420 mg Q2W | Time to Achievement of 50%, 75% or 90% Reduction From Day 1 in Eczema Area and Severity Index (EASI 50/75/90) | Time to EASI 75 | 6.429 Weeks |