Atopic Dermatitis, Healthy Volunteers
Conditions
Keywords
atopic dermatitis, skin diseases, healthy volunteer
Brief summary
This study is a single dose escalation study of tezepelumab (AMG 157) in healthy adults (Part A) and adults with moderate to severe atopic dermatitis (Part B). The purpose of the study is to evaluate the safety, tolerability, immunogenicity and pharmacokinetics of tezepelumab.
Interventions
DRUGTezepelumab
Administered by subcutaneous or intravenous injection
DRUGPlacebo
Matching placebo administered by subcutaneous or intravenous injection.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Escalating dose cohorts will be enrolled sequentially based on a blinded review of safety data up to day 15 of the previous dose cohort with consideration of predefined stopping rules. The first 2 participants in Cohort 1 will be a sentinel pair, randomized at a 1:1 ratio to receive either tezepelumab or placebo and monitored for safety and tolerability. Once the safety in the sentinel pair is confirmed the subsequent six participants will be randomized at a 5:1 ratio for tezepelumab or placebo treatment. In cohorts 2 through 8 (escalating doses, healthy subjects), participants will be randomized to receive tezepelumab or placebo at a 6:2 ratio. In cohort 9 (700 mg IV, atopic dermatitis subjects),a sentinel pair will again be used to first establish safety, and the subsequent 10 participants will be randomized to receive tezepelumab or placebo at a ratio of 8:2, for a total of 12 evaluable participants in this cohort.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject must sign an Institutional Review Board (IRB) approved informed consent form before any study specific procedures * Subjects must be aged between 18 and 45 years, inclusive (Part A only) * Female subjects must be of non-reproductive potential * Male subjects with partners of childbearing potential should inform their partner of their participation in this clinical study and use highly effective methods of birth control during the study * Healthy subjects must have a body mass index (BMI) between 18 to 32 kg/m\^2, inclusive * Subject must have normal or clinically acceptable physical examination, clinical laboratory tests and electrocardiogram (ECG) results * For Part B, subject must have active atopic dermatitis (AD) affecting ≥ 10% body surface area; Eczema Area and Severity Index (EASI) score ≥ 15, aged between 18 and 60 years, inclusive and BMI between 18 and 35 kg/m\^2, inclusive
Exclusion criteria
* Subject who has history or evidence of a clinically significant disorder, condition or disease that, in the opinion of the Investigator in consultation with the Amgen physician, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion * Subject who has evidence of any active or suspected bacterial, viral, fungal or parasitic infections within the past 30 days prior to randomization * Subject who has known positive tuberculin skin test or recent (within 6 months from randomization) exposure to an individual with active tuberculosis * Subject who has history of malignancy within 5 years before randomization * Subject who has history of significant dermatological conditions (except for atopic dermatitis in Part B) * Subject who has previously received any investigational drug (or is currently using an investigational device) within 30 days prior to randomization * Subject who has tested positive for drugs and/or alcohol use at screening or before randomization * Female subjects who are pregnant or lactating * Subject who has used nicotine or tobacco containing products during 6 months before randomization and during the study (except for Part B below) * Subject has known type I/II diabetes * Subject used nonprescription drugs within 14 days prior to randomization and during the study * Subject used any cytotoxic or immunosuppressive drugs with 30 days or 5 half-lives prior to randomization and during the study * Subject previously received a monoclonal antibody * Subject donated blood or had loss of blood of equal to or greater than 500 mL with 2 months of screening * Subject positive for human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C antibodies * Subject has any condition that might compromise informed consent or compliance to the protocol * For atopic dermatitis subjects in Part B (Cohorts 9 and 10) only, additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | For Part A Tezepelumab/Placebo 2.1 mg, 7 mg, 21 mg, 70 mg, and 210 mg SC: 85 days. For Part A Tezepelumab/Placebo 420 mg SC, 210 mg IV, and 700 mg IV and Part B: 113 days | Adverse events (AEs) include any untoward medical occurrence in a trial participant administered a study drug and does not necessarily have a causal relationship with this treatment. AEs include worsening of a pre-existing medical condition and laboratory value changes requiring therapy or adjustment in prior therapy. AEs were assessed for severity according to the Common Terminology Criteria for Adverse Events (CTCAE), Version 3, where Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening AE and Grade 5 = death due to AE. Relationship to study treatment was determined by the investigator. A serious adverse event (SAE) is defined as an AE that met 1 or more of below criteria: * was fatal; * was life threatening; * required in-patient hospitalization or prolongation of existing hospitalization; * resulted in persistent or significant disability/incapacity; * was a congenital anomaly/birth defect; * other significant medical hazard. |
| Number of Participants Who Developed Anti-tezepelumab Antibodies | Blood samples for the measurement of antibodies were collected on Days 29, 57, 85, and (for cohorts who received 420 mg Tezepelumab/placebo SC or any IV dose) 113. | All study samples (tezepelumab and placebo) were tested using an electrochemiluminescence (ECL) based immunoassay to detect and confirm the presence of antibodies capable of binding to tezepelumab. Samples identified as positive in the immunoassay were tested in a receptor-binding ECL-based assay to detect neutralizing or inhibitory effects toward tezepelumab. The number of participants with positive anti-tezepelumab binding antibodies / neutralizing antibodies at any time post-baseline with a negative or no result at baseline is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Time of Maximum Observed Concentration (Tmax) of Tezepelumab | Day 1 predose, 0.25, 0.5, 1, 4, 8, 72 hours postdose and days, 7, 15, 22, 29, 43, 57, 71, 85, and 113. | Tmax was estimated based on the serum concentrations of tezepelumab using noncompartmental methods. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL. |
| Part B: Maximum Observed Concentration (Cmax) of Tezepelumab | Day 1 predose, 0.25, 0.5, 1, 4, 8, 72 hours postdose and days, 7, 15, 22, 29, 43, 57, 71, 85, and 113. | Cmax was estimated based on the serum concentrations of tezepelumab using noncompartmental methods. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL. |
| Part B: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tezepelumab | Day 1 predose, 0.25, 0.5, 1, 4, 8, 72 hours postdose and days, 7, 15, 22, 29, 43, 57, 71, 85, and 113. | The PK parameter AUC0-t was estimated based on the serum concentrations of tezepelumab using noncompartmental methods and the linear/log trapezoidal method. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL. |
| Part B: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Tezepelumab | Day 1 predose, 0.25, 0.5, 1, 4, 8, 72 hours postdose and days, 7, 15, 22, 29, 43, 57, 71, 85, and 113. | The PK parameter AUCinf was estimated based on the serum concentrations of tezepelumab using noncompartmental methods and the linear/log trapezoidal method. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL. |
| Part B: Elimination Half-life (t1/2) of Tezepelumab | Day 1 predose, 0.25, 0.5, 1, 4, 8, 72 hours postdose and days, 7, 15, 22, 29, 43, 57, 71, 85, and 113. | Elimination half-life was estimated based on the serum concentrations of tezepelumab using noncompartmental methods based on the terminal phase of the concentration-time profile. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL. |
| Part A: Time of Maximum Observed Concentration (Tmax) of Tezepelumab | Day 1 predose, 0.25, 0.5, and 1 hour after start of infusion (for IV cohorts only), 4, 8, 24, 48, 72 hours postdose and days 5, 6, 7, 11, 15, 22, 29, 43, 57, 71, 85, and (for cohorts who received 420 mg tezepelumab SC or any IV dose) 113. | The time at which the maximum concentration of tezepelumab was observed was estimated based on the serum concentrations of tezepelumab using noncompartmental methods. The concentration of tezepelumab in human serum was measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification of the assay was 10 ng/mL. |
| Part A: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Tezepelumab | Day 1 predose, 0.25, 0.5, and 1 hour after start of infusion (for IV cohorts only), 4, 8, 24, 48, 72 hours postdose and days 5, 6, 7, 11, 15, 22, 29, 43, 57, 71, 85, and (for cohorts who received 420 mg tezepelumab SC or any IV dose) 113. | The PK parameter AUCinf was estimated based on the serum concentrations of tezepelumab using noncompartmental methods and the linear/log trapezoidal method. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL. |
| Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tezepelumab | Day 1 predose, 0.25, 0.5, and 1 hour after start of infusion (for IV cohorts only), 4, 8, 24, 48, 72 hours postdose and days 5, 6, 7, 11, 15, 22, 29, 43, 57, 71, 85, and (for cohorts who received 420 mg tezepelumab SC or any IV dose) 113. | The PK parameter AUC0-t was estimated based on the serum concentrations of tezepelumab using noncompartmental methods and the linear/log trapezoidal method. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL. |
| Part B: Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Eczema Area and Severity Index (EASI 50) Score | Baseline and days 15, 29, 43, 57, 85, and 113 | EASI is a tool used to measure the severity of AD. The index involves an assessment of the average intensity of 4 clinical signs (erythema, infiltration/papulation, excoriations, and lichenification) at 4 body areas (head/neck, upper extremities, trunk, lower extremities) assessed on a scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe. The percent of affected area for each of the 4 body areas is also assessed using the following 6-point scale: 0 = 0%, 1 = \< 10%, 2 =10% to 29%, 3 = 30% to 49%, 4 = 50% to 69%, 5 = 70% to 89%, 6 = 90% to 100%. The total score for each body region is obtained by multiplying the sum of the severity scores of the 4 clinical signs by the area score, with adjustment for the proportion of the body region to the whole body. The sum of the scores for each body region gives the total EASI score, which ranges from 0 to 72, with higher scores indicating greater disease severity. |
| Part B: Percentage of Participants Achieving at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) Score | Baseline and days 15, 29, 43, 57, 85, and 113 | EASI is a tool used to measure the severity of AD. The index involves an assessment of the average intensity of 4 clinical signs (erythema, infiltration/papulation, excoriations, and lichenification) at 4 body areas (head/neck, upper extremities, trunk, lower extremities) assessed on a scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe. The percent of affected area for each of the 4 body areas is also assessed using the following 6-point scale: 0 = 0%, 1 = \< 10%, 2 =10% to 29%, 3 = 30% to 49%, 4 = 50% to 69%, 5 = 70% to 89%, 6 = 90% to 100%. The total score for each body region is obtained by multiplying the sum of the severity scores of the 4 clinical signs by the area score, with adjustment for the proportion of the body region to the whole body. The sum of the scores for each body region gives the total EASI score, which ranges from 0 to 72, with higher scores indicating greater disease severity. |
| Part B: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score | Baseline and days 15, 29, 43, 57, 85, and 113 | EASI is a tool used to measure the severity of AD. The index involves an assessment of the intensity of 4 clinical signs (erythema, infiltration/papulation, excoriations, and lichenification) at 4 body areas (head/neck, upper extremities, trunk, lower extremities) assessed on a scale from 0 (none) to 3 (severe). The percent affected area for each of the 4 body areas is assessed on a 6-point scale from 0 (0%) to 6 (90% to 100%). The total score for each body region is obtained by multiplying the sum of the severity scores of the 4 clinical signs by the area score, with adjustment for the proportion of the body region to the whole body. The total EASI score is the sum of the scores for each body region, and ranges from 0 to 72, with higher scores indicating greater disease severity. Percent change from baseline = \[(Post-baseline Value - Baseline Value) / Baseline Value\] x 100. A negative change from baseline indicates improvement. |
| Part B: Change From Baseline in Investigator's Global Assessment (IGA) | Baseline and days 15, 29, 43, 57, 85, and 113 | IGA score is a static 6-point measure of disease activity based on an overall assessment of skin lesions. The IGA was scored on a scale of 0 to 5, where 0 (clear) = no inflammatory signs of AD; 1. (almost clear) = just perceptible erythema and just perceptible papulation/infiltration; 2. (mild) = mild erythema and mild papulation and infiltration; 3. (moderate) = moderate erythema and moderate papulation and infiltration; 4. (severe) = severe disease with severe erythema and severe papulation and infiltration; 5. (very severe) = severe disease with severe erythema and severe papulation and infiltration with oozing/crusting. A negative change from baseline indicates improvement. |
| Part A: Maximum Observed Concentration (Cmax) of Tezepelumab | Day 1 predose, 0.25, 0.5, and 1 hour after start of infusion (for IV cohorts only), 4, 8, 24, 48, 72 hours postdose and days 5, 6, 7, 11, 15, 22, 29, 43, 57, 71, 85, and (for cohorts who received 420 mg tezepelumab SC or any IV dose) 113. | The maximum observed serum concentration of tezepelumab was estimated based on the serum concentrations of tezepelumab using noncompartmental methods. The concentration of tezepelumab in human serum was measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification of the assay was 10 ng/mL. |
| Part A: Elimination Half-life (t1/2) of Tezepelumab | Day 1 predose, 0.25, 0.5, and 1 hour after start of infusion (for IV cohorts only), 4, 8, 24, 48, 72 hours postdose and days 5, 6, 7, 11, 15, 22, 29, 43, 57, 71, 85, and (for cohorts who received 420 mg tezepelumab SC or any IV dose) 113. | Elimination half-life was estimated based on the serum concentrations of tezepelumab using noncompartmental methods based on the terminal phase of the concentration-time profile. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL. |
Participant flow
Recruitment details
This study was a single-ascending dose (SAD) study of tezepelumab in healthy adults (Part A; Cohorts 1-8) and adults with moderate to severe atopic dermatitis (AD) (Part B; Cohort 9). The study was conducted at seven centers in the United States, including one center that conducted the testing in all healthy adults and six centers that performed the study in AD participants. Dose escalation was based on blinded review of safety data up to day 15 from the previous cohort.
Pre-assignment details
In Part A the first 2 participants enrolled in Cohort 1 were randomized in a 1:1 ratio and subsequent participants in this cohort were randomized in a 5:1 ratio to receive tezepelumab or placebo. For Cohorts 2 to 8 in Part A, participants were randomized in a 6:2 ratio to receive tezepelumab or placebo. In Part B, the first 2 participants were randomized in a 1:1 ratio, and subsequent participants in Cohort 9 were randomized in an 8:2 ratio to receive tezepelumab or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Tezepelumab 2.1 mg SC Healthy participants received a single dose of 2.1 mg tezepelumab administered subcutaneously (SC). | 6 |
| Part A: Tezepelumab 7 mg SC Healthy participants received a single dose of 7 mg tezepelumab administered subcutaneously. | 6 |
| Part A: Tezepelumab 21 mg SC Healthy participants received a single dose of 21 mg tezepelumab administered subcutaneously. | 6 |
| Part A: Tezepelumab 70 mg SC Healthy participants received a single dose of 70 mg tezepelumab administered subcutaneously. | 6 |
| Part A: Tezepelumab 210 mg SC Healthy participants received a single dose of 210 mg tezepelumab administered subcutaneously. | 6 |
| Part A: Tezepelumab 420 mg SC Healthy participants received a single dose of 420 mg tezepelumab administered subcutaneously. | 6 |
| Part A: Tezepelumab 210 mg IV Healthy participants received a single dose of 210 mg tezepelumab administered intravenously. | 6 |
| Part A: Tezepelumab 700 mg IV Healthy participants received a single dose of 700 mg tezepelumab administered intravenously. | 6 |
| Part A: Placebo Healthy participants received a single dose of placebo to tezepelumab administered subcutaneously or intravenously. | 16 |
| Part B: Tezepelumab 700 mg IV Participants with atopic dermatitis received a single dose of 700 mg tezepelumab administered intravenously. | 9 |
| Part B: Placebo IV Participants with atopic dermatitis received a single dose of placebo to tezepelumab administered intravenously. | 3 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Ineligibility Determined | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part A: Tezepelumab 2.1 mg SC | Part A: Tezepelumab 7 mg SC | Part A: Tezepelumab 21 mg SC | Part A: Tezepelumab 70 mg SC | Part A: Tezepelumab 210 mg SC | Part A: Tezepelumab 420 mg SC | Part A: Tezepelumab 210 mg IV | Part A: Tezepelumab 700 mg IV | Part A: Placebo | Part B: Tezepelumab 700 mg IV | Part B: Placebo IV | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 28.2 years STANDARD_DEVIATION 4.9 | 32.2 years STANDARD_DEVIATION 2.1 | 36.8 years STANDARD_DEVIATION 2.6 | 28.3 years STANDARD_DEVIATION 4.9 | 33.7 years STANDARD_DEVIATION 4.1 | 37.0 years STANDARD_DEVIATION 3.7 | 33.0 years STANDARD_DEVIATION 7.5 | 30.2 years STANDARD_DEVIATION 3.6 | 32.3 years STANDARD_DEVIATION 7.6 | 48.1 years STANDARD_DEVIATION 11.3 | 45.3 years STANDARD_DEVIATION 5.5 | 34.8 years STANDARD_DEVIATION 8.6 |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 3 Participants | 5 Participants | 5 Participants | 4 Participants | 2 Participants | 2 Participants | 4 Participants | 1 Participants | 11 Participants | 0 Participants | 0 Participants | 37 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 4 Participants | 8 Participants | 2 Participants | 27 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 5 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 0 Participants | 16 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 1 Participants | 5 Participants | 6 Participants | 6 Participants | 5 Participants | 5 Participants | 13 Participants | 7 Participants | 3 Participants | 60 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 | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 6 | 5 / 6 | 1 / 6 | 6 / 6 | 2 / 6 | 3 / 6 | 4 / 6 | 5 / 6 | 8 / 12 | 3 / 4 | 7 / 9 | 3 / 3 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 4 | 0 / 9 | 1 / 3 |
Outcome results
Primary
Number of Participants Who Developed Anti-tezepelumab Antibodies
All study samples (tezepelumab and placebo) were tested using an electrochemiluminescence (ECL) based immunoassay to detect and confirm the presence of antibodies capable of binding to tezepelumab. Samples identified as positive in the immunoassay were tested in a receptor-binding ECL-based assay to detect neutralizing or inhibitory effects toward tezepelumab. The number of participants with positive anti-tezepelumab binding antibodies / neutralizing antibodies at any time post-baseline with a negative or no result at baseline is reported.
Time frame: Blood samples for the measurement of antibodies were collected on Days 29, 57, 85, and (for cohorts who received 420 mg Tezepelumab/placebo SC or any IV dose) 113.
Population: All participants who received at least 1 dose of study drug with a postbaseline result.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Tezepelumab 2.1 mg SC | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab binding antibodies | 0 Participants |
| Part A: Tezepelumab 2.1 mg SC | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab neutralizing antibodies | 0 Participants |
| Part A: Tezepelumab 7 mg SC | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab binding antibodies | 0 Participants |
| Part A: Tezepelumab 7 mg SC | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab neutralizing antibodies | 0 Participants |
| Part A: Tezepelumab 21 mg SC | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab binding antibodies | 0 Participants |
| Part A: Tezepelumab 21 mg SC | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab neutralizing antibodies | 0 Participants |
| Part A: Tezepelumab 70 mg SC | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab binding antibodies | 0 Participants |
| Part A: Tezepelumab 70 mg SC | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab neutralizing antibodies | 0 Participants |
| Part A: Tezepelumab 210 mg SC | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab binding antibodies | 0 Participants |
| Part A: Tezepelumab 210 mg SC | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab neutralizing antibodies | 0 Participants |
| Part A: Tezepelumab 420 mg SC | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab neutralizing antibodies | 0 Participants |
| Part A: Tezepelumab 420 mg SC | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab binding antibodies | 0 Participants |
| Part A: Tezepelumab 210 mg IV | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab neutralizing antibodies | 0 Participants |
| Part A: Tezepelumab 210 mg IV | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab binding antibodies | 0 Participants |
| Part A: Tezepelumab 700 mg IV | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab binding antibodies | 0 Participants |
| Part A: Tezepelumab 700 mg IV | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab neutralizing antibodies | 0 Participants |
| Part A: Placebo SC | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab binding antibodies | 1 Participants |
| Part A: Placebo SC | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab neutralizing antibodies | 0 Participants |
| Part A: Placebo IV | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab binding antibodies | 0 Participants |
| Part A: Placebo IV | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab neutralizing antibodies | 0 Participants |
| Part B: Tezepelumab 700 mg IV | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab binding antibodies | 0 Participants |
| Part B: Tezepelumab 700 mg IV | Number of Participants Who Developed Anti-tezepelumab Antibodies | Anti-tezepelumab neutralizing antibodies | 0 Participants |
Primary
Number of Participants With Adverse Events
Adverse events (AEs) include any untoward medical occurrence in a trial participant administered a study drug and does not necessarily have a causal relationship with this treatment. AEs include worsening of a pre-existing medical condition and laboratory value changes requiring therapy or adjustment in prior therapy. AEs were assessed for severity according to the Common Terminology Criteria for Adverse Events (CTCAE), Version 3, where Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening AE and Grade 5 = death due to AE. Relationship to study treatment was determined by the investigator. A serious adverse event (SAE) is defined as an AE that met 1 or more of below criteria: * was fatal; * was life threatening; * required in-patient hospitalization or prolongation of existing hospitalization; * resulted in persistent or significant disability/incapacity; * was a congenital anomaly/birth defect; * other significant medical hazard.
Time frame: For Part A Tezepelumab/Placebo 2.1 mg, 7 mg, 21 mg, 70 mg, and 210 mg SC: 85 days. For Part A Tezepelumab/Placebo 420 mg SC, 210 mg IV, and 700 mg IV and Part B: 113 days
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Tezepelumab 2.1 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Part A: Tezepelumab 2.1 mg SC | Number of Participants With Adverse Events | Any adverse event | 3 Participants |
| Part A: Tezepelumab 2.1 mg SC | Number of Participants With Adverse Events | Treatment-related adverse event | 1 Participants |
| Part A: Tezepelumab 2.1 mg SC | Number of Participants With Adverse Events | Fatal adverse event | 0 Participants |
| Part A: Tezepelumab 2.1 mg SC | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Part A: Tezepelumab 2.1 mg SC | Number of Participants With Adverse Events | AE leading to study drug discontinuation | 0 Participants |
| Part A: Tezepelumab 7 mg SC | Number of Participants With Adverse Events | Treatment-related adverse event | 0 Participants |
| Part A: Tezepelumab 7 mg SC | Number of Participants With Adverse Events | Fatal adverse event | 0 Participants |
| Part A: Tezepelumab 7 mg SC | Number of Participants With Adverse Events | Any adverse event | 5 Participants |
| Part A: Tezepelumab 7 mg SC | Number of Participants With Adverse Events | AE leading to study drug discontinuation | 0 Participants |
| Part A: Tezepelumab 7 mg SC | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Part A: Tezepelumab 7 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Part A: Tezepelumab 21 mg SC | Number of Participants With Adverse Events | AE leading to study drug discontinuation | 0 Participants |
| Part A: Tezepelumab 21 mg SC | Number of Participants With Adverse Events | Fatal adverse event | 0 Participants |
| Part A: Tezepelumab 21 mg SC | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Part A: Tezepelumab 21 mg SC | Number of Participants With Adverse Events | Any adverse event | 1 Participants |
| Part A: Tezepelumab 21 mg SC | Number of Participants With Adverse Events | Treatment-related adverse event | 0 Participants |
| Part A: Tezepelumab 21 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Part A: Tezepelumab 70 mg SC | Number of Participants With Adverse Events | Any adverse event | 6 Participants |
| Part A: Tezepelumab 70 mg SC | Number of Participants With Adverse Events | Treatment-related adverse event | 0 Participants |
| Part A: Tezepelumab 70 mg SC | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Part A: Tezepelumab 70 mg SC | Number of Participants With Adverse Events | Fatal adverse event | 0 Participants |
| Part A: Tezepelumab 70 mg SC | Number of Participants With Adverse Events | AE leading to study drug discontinuation | 0 Participants |
| Part A: Tezepelumab 70 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Part A: Tezepelumab 210 mg SC | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Part A: Tezepelumab 210 mg SC | Number of Participants With Adverse Events | Treatment-related adverse event | 2 Participants |
| Part A: Tezepelumab 210 mg SC | Number of Participants With Adverse Events | Any adverse event | 2 Participants |
| Part A: Tezepelumab 210 mg SC | Number of Participants With Adverse Events | AE leading to study drug discontinuation | 0 Participants |
| Part A: Tezepelumab 210 mg SC | Number of Participants With Adverse Events | Fatal adverse event | 0 Participants |
| Part A: Tezepelumab 210 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Part A: Tezepelumab 420 mg SC | Number of Participants With Adverse Events | Fatal adverse event | 0 Participants |
| Part A: Tezepelumab 420 mg SC | Number of Participants With Adverse Events | Any adverse event | 3 Participants |
| Part A: Tezepelumab 420 mg SC | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Part A: Tezepelumab 420 mg SC | Number of Participants With Adverse Events | AE leading to study drug discontinuation | 0 Participants |
| Part A: Tezepelumab 420 mg SC | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Part A: Tezepelumab 420 mg SC | Number of Participants With Adverse Events | Treatment-related adverse event | 1 Participants |
| Part A: Tezepelumab 210 mg IV | Number of Participants With Adverse Events | Any adverse event | 4 Participants |
| Part A: Tezepelumab 210 mg IV | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Part A: Tezepelumab 210 mg IV | Number of Participants With Adverse Events | Fatal adverse event | 0 Participants |
| Part A: Tezepelumab 210 mg IV | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Part A: Tezepelumab 210 mg IV | Number of Participants With Adverse Events | AE leading to study drug discontinuation | 0 Participants |
| Part A: Tezepelumab 210 mg IV | Number of Participants With Adverse Events | Treatment-related adverse event | 2 Participants |
| Part A: Tezepelumab 700 mg IV | Number of Participants With Adverse Events | Fatal adverse event | 0 Participants |
| Part A: Tezepelumab 700 mg IV | Number of Participants With Adverse Events | AE leading to study drug discontinuation | 0 Participants |
| Part A: Tezepelumab 700 mg IV | Number of Participants With Adverse Events | Treatment-related adverse event | 0 Participants |
| Part A: Tezepelumab 700 mg IV | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Part A: Tezepelumab 700 mg IV | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Part A: Tezepelumab 700 mg IV | Number of Participants With Adverse Events | Any adverse event | 5 Participants |
| Part A: Placebo SC | Number of Participants With Adverse Events | Any adverse event | 8 Participants |
| Part A: Placebo SC | Number of Participants With Adverse Events | Fatal adverse event | 0 Participants |
| Part A: Placebo SC | Number of Participants With Adverse Events | Treatment-related adverse event | 4 Participants |
| Part A: Placebo SC | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Part A: Placebo SC | Number of Participants With Adverse Events | AE leading to study drug discontinuation | 0 Participants |
| Part A: Placebo SC | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Part A: Placebo IV | Number of Participants With Adverse Events | AE leading to study drug discontinuation | 0 Participants |
| Part A: Placebo IV | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Part A: Placebo IV | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Part A: Placebo IV | Number of Participants With Adverse Events | Fatal adverse event | 0 Participants |
| Part A: Placebo IV | Number of Participants With Adverse Events | Any adverse event | 3 Participants |
| Part A: Placebo IV | Number of Participants With Adverse Events | Treatment-related adverse event | 1 Participants |
| Part B: Tezepelumab 700 mg IV | Number of Participants With Adverse Events | Any adverse event | 7 Participants |
| Part B: Tezepelumab 700 mg IV | Number of Participants With Adverse Events | AE leading to study drug discontinuation | 0 Participants |
| Part B: Tezepelumab 700 mg IV | Number of Participants With Adverse Events | Serious adverse event | 0 Participants |
| Part B: Tezepelumab 700 mg IV | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Part B: Tezepelumab 700 mg IV | Number of Participants With Adverse Events | Treatment-related adverse event | 3 Participants |
| Part B: Tezepelumab 700 mg IV | Number of Participants With Adverse Events | Fatal adverse event | 0 Participants |
| Part B: Placebo IV | Number of Participants With Adverse Events | AE leading to study drug discontinuation | 0 Participants |
| Part B: Placebo IV | Number of Participants With Adverse Events | Fatal adverse event | 0 Participants |
| Part B: Placebo IV | Number of Participants With Adverse Events | Any adverse event | 3 Participants |
| Part B: Placebo IV | Number of Participants With Adverse Events | Serious adverse event | 1 Participants |
| Part B: Placebo IV | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Part B: Placebo IV | Number of Participants With Adverse Events | Treatment-related adverse event | 3 Participants |
Secondary
Part A: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Tezepelumab
The PK parameter AUCinf was estimated based on the serum concentrations of tezepelumab using noncompartmental methods and the linear/log trapezoidal method. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.
Time frame: Day 1 predose, 0.25, 0.5, and 1 hour after start of infusion (for IV cohorts only), 4, 8, 24, 48, 72 hours postdose and days 5, 6, 7, 11, 15, 22, 29, 43, 57, 71, 85, and (for cohorts who received 420 mg tezepelumab SC or any IV dose) 113.
Population: Participants in Part A who received tezepelumab and had a sufficient number of serum concentration measurements for computing the PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Tezepelumab 2.1 mg SC | Part A: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Tezepelumab | 8.69 day*μg/mL | Standard Deviation 1.97 |
| Part A: Tezepelumab 7 mg SC | Part A: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Tezepelumab | 36.6 day*μg/mL | Standard Deviation 4.6 |
| Part A: Tezepelumab 21 mg SC | Part A: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Tezepelumab | 84.6 day*μg/mL | Standard Deviation 37.9 |
| Part A: Tezepelumab 70 mg SC | Part A: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Tezepelumab | 303 day*μg/mL | Standard Deviation 70.3 |
| Part A: Tezepelumab 210 mg SC | Part A: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Tezepelumab | 976 day*μg/mL | Standard Deviation 409 |
| Part A: Tezepelumab 420 mg SC | Part A: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Tezepelumab | 2140 day*μg/mL | Standard Deviation 677 |
| Part A: Tezepelumab 210 mg IV | Part A: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Tezepelumab | 1200 day*μg/mL | Standard Deviation 208 |
| Part A: Tezepelumab 700 mg IV | Part A: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Tezepelumab | 3530 day*μg/mL | Standard Deviation 322 |
Secondary
Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tezepelumab
The PK parameter AUC0-t was estimated based on the serum concentrations of tezepelumab using noncompartmental methods and the linear/log trapezoidal method. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.
Time frame: Day 1 predose, 0.25, 0.5, and 1 hour after start of infusion (for IV cohorts only), 4, 8, 24, 48, 72 hours postdose and days 5, 6, 7, 11, 15, 22, 29, 43, 57, 71, 85, and (for cohorts who received 420 mg tezepelumab SC or any IV dose) 113.
Population: Participants in Part A who received tezepelumab and had a sufficient number of serum concentration measurements for computing the PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Tezepelumab 2.1 mg SC | Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tezepelumab | 8.12 day*μg/mL | Standard Deviation 1.96 |
| Part A: Tezepelumab 7 mg SC | Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tezepelumab | 32.9 day*μg/mL | Standard Deviation 2.75 |
| Part A: Tezepelumab 21 mg SC | Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tezepelumab | 76.7 day*μg/mL | Standard Deviation 31.6 |
| Part A: Tezepelumab 70 mg SC | Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tezepelumab | 278 day*μg/mL | Standard Deviation 64.3 |
| Part A: Tezepelumab 210 mg SC | Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tezepelumab | 867 day*μg/mL | Standard Deviation 349 |
| Part A: Tezepelumab 420 mg SC | Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tezepelumab | 2050 day*μg/mL | Standard Deviation 627 |
| Part A: Tezepelumab 210 mg IV | Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tezepelumab | 1150 day*μg/mL | Standard Deviation 176 |
| Part A: Tezepelumab 700 mg IV | Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tezepelumab | 3440 day*μg/mL | Standard Deviation 253 |
Secondary
Part A: Elimination Half-life (t1/2) of Tezepelumab
Elimination half-life was estimated based on the serum concentrations of tezepelumab using noncompartmental methods based on the terminal phase of the concentration-time profile. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.
Time frame: Day 1 predose, 0.25, 0.5, and 1 hour after start of infusion (for IV cohorts only), 4, 8, 24, 48, 72 hours postdose and days 5, 6, 7, 11, 15, 22, 29, 43, 57, 71, 85, and (for cohorts who received 420 mg tezepelumab SC or any IV dose) 113.
Population: Participants in Part A who received tezepelumab and had a sufficient number of serum concentration measurements for computing the PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Tezepelumab 2.1 mg SC | Part A: Elimination Half-life (t1/2) of Tezepelumab | 19.9 days | Standard Deviation 4.81 |
| Part A: Tezepelumab 7 mg SC | Part A: Elimination Half-life (t1/2) of Tezepelumab | 23.4 days | Standard Deviation 4.3 |
| Part A: Tezepelumab 21 mg SC | Part A: Elimination Half-life (t1/2) of Tezepelumab | 22.7 days | Standard Deviation 4.81 |
| Part A: Tezepelumab 70 mg SC | Part A: Elimination Half-life (t1/2) of Tezepelumab | 22.5 days | Standard Deviation 1.35 |
| Part A: Tezepelumab 210 mg SC | Part A: Elimination Half-life (t1/2) of Tezepelumab | 25.7 days | Standard Deviation 5.52 |
| Part A: Tezepelumab 420 mg SC | Part A: Elimination Half-life (t1/2) of Tezepelumab | 23.3 days | Standard Deviation 2.89 |
| Part A: Tezepelumab 210 mg IV | Part A: Elimination Half-life (t1/2) of Tezepelumab | 24.5 days | Standard Deviation 6.28 |
| Part A: Tezepelumab 700 mg IV | Part A: Elimination Half-life (t1/2) of Tezepelumab | 20.7 days | Standard Deviation 6.44 |
Secondary
Part A: Maximum Observed Concentration (Cmax) of Tezepelumab
The maximum observed serum concentration of tezepelumab was estimated based on the serum concentrations of tezepelumab using noncompartmental methods. The concentration of tezepelumab in human serum was measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification of the assay was 10 ng/mL.
Time frame: Day 1 predose, 0.25, 0.5, and 1 hour after start of infusion (for IV cohorts only), 4, 8, 24, 48, 72 hours postdose and days 5, 6, 7, 11, 15, 22, 29, 43, 57, 71, 85, and (for cohorts who received 420 mg tezepelumab SC or any IV dose) 113.
Population: Participants in Part A who received tezepelumab and had a sufficient number of serum concentration measurements for computing the PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Tezepelumab 2.1 mg SC | Part A: Maximum Observed Concentration (Cmax) of Tezepelumab | 0.257 μg/mL | Standard Deviation 0.0824 |
| Part A: Tezepelumab 7 mg SC | Part A: Maximum Observed Concentration (Cmax) of Tezepelumab | 0.792 μg/mL | Standard Deviation 0.0593 |
| Part A: Tezepelumab 21 mg SC | Part A: Maximum Observed Concentration (Cmax) of Tezepelumab | 2.01 μg/mL | Standard Deviation 0.62 |
| Part A: Tezepelumab 70 mg SC | Part A: Maximum Observed Concentration (Cmax) of Tezepelumab | 7.82 μg/mL | Standard Deviation 2.25 |
| Part A: Tezepelumab 210 mg SC | Part A: Maximum Observed Concentration (Cmax) of Tezepelumab | 23.6 μg/mL | Standard Deviation 10.3 |
| Part A: Tezepelumab 420 mg SC | Part A: Maximum Observed Concentration (Cmax) of Tezepelumab | 58.0 μg/mL | Standard Deviation 19.3 |
| Part A: Tezepelumab 210 mg IV | Part A: Maximum Observed Concentration (Cmax) of Tezepelumab | 64.4 μg/mL | Standard Deviation 10.2 |
| Part A: Tezepelumab 700 mg IV | Part A: Maximum Observed Concentration (Cmax) of Tezepelumab | 219 μg/mL | Standard Deviation 38.3 |
Secondary
Part A: Time of Maximum Observed Concentration (Tmax) of Tezepelumab
The time at which the maximum concentration of tezepelumab was observed was estimated based on the serum concentrations of tezepelumab using noncompartmental methods. The concentration of tezepelumab in human serum was measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification of the assay was 10 ng/mL.
Time frame: Day 1 predose, 0.25, 0.5, and 1 hour after start of infusion (for IV cohorts only), 4, 8, 24, 48, 72 hours postdose and days 5, 6, 7, 11, 15, 22, 29, 43, 57, 71, 85, and (for cohorts who received 420 mg tezepelumab SC or any IV dose) 113.
Population: Participants in Part A who received tezepelumab and had a sufficient number of serum concentration measurements for computing the pharmacokinetic (PK) parameter.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Tezepelumab 2.1 mg SC | Part A: Time of Maximum Observed Concentration (Tmax) of Tezepelumab | 190.94 hours |
| Part A: Tezepelumab 7 mg SC | Part A: Time of Maximum Observed Concentration (Tmax) of Tezepelumab | 237.09 hours |
| Part A: Tezepelumab 21 mg SC | Part A: Time of Maximum Observed Concentration (Tmax) of Tezepelumab | 142.10 hours |
| Part A: Tezepelumab 70 mg SC | Part A: Time of Maximum Observed Concentration (Tmax) of Tezepelumab | 130.87 hours |
| Part A: Tezepelumab 210 mg SC | Part A: Time of Maximum Observed Concentration (Tmax) of Tezepelumab | 93.65 hours |
| Part A: Tezepelumab 420 mg SC | Part A: Time of Maximum Observed Concentration (Tmax) of Tezepelumab | 80.89 hours |
| Part A: Tezepelumab 210 mg IV | Part A: Time of Maximum Observed Concentration (Tmax) of Tezepelumab | 1.13 hours |
| Part A: Tezepelumab 700 mg IV | Part A: Time of Maximum Observed Concentration (Tmax) of Tezepelumab | 1.04 hours |
Secondary
Part B: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Tezepelumab
The PK parameter AUCinf was estimated based on the serum concentrations of tezepelumab using noncompartmental methods and the linear/log trapezoidal method. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.
Time frame: Day 1 predose, 0.25, 0.5, 1, 4, 8, 72 hours postdose and days, 7, 15, 22, 29, 43, 57, 71, 85, and 113.
Population: Participants in Part B who received tezepelumab and had a sufficient number of serum concentration measurements for computing the PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Tezepelumab 2.1 mg SC | Part B: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Tezepelumab | 3830 day*μg/mL | Standard Deviation 1230 |
Secondary
Part B: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tezepelumab
The PK parameter AUC0-t was estimated based on the serum concentrations of tezepelumab using noncompartmental methods and the linear/log trapezoidal method. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.
Time frame: Day 1 predose, 0.25, 0.5, 1, 4, 8, 72 hours postdose and days, 7, 15, 22, 29, 43, 57, 71, 85, and 113.
Population: Participants in Part B who received tezepelumab and had a sufficient number of serum concentration measurements for computing the PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Tezepelumab 2.1 mg SC | Part B: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tezepelumab | 3660 day*μg/mL | Standard Deviation 990 |
Secondary
Part B: Change From Baseline in Investigator's Global Assessment (IGA)
IGA score is a static 6-point measure of disease activity based on an overall assessment of skin lesions. The IGA was scored on a scale of 0 to 5, where 0 (clear) = no inflammatory signs of AD; 1. (almost clear) = just perceptible erythema and just perceptible papulation/infiltration; 2. (mild) = mild erythema and mild papulation and infiltration; 3. (moderate) = moderate erythema and moderate papulation and infiltration; 4. (severe) = severe disease with severe erythema and severe papulation and infiltration; 5. (very severe) = severe disease with severe erythema and severe papulation and infiltration with oozing/crusting. A negative change from baseline indicates improvement.
Time frame: Baseline and days 15, 29, 43, 57, 85, and 113
Population: All participants in Part B who received at least 1 dose of study drug and with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Tezepelumab 2.1 mg SC | Part B: Change From Baseline in Investigator's Global Assessment (IGA) | Day 15 | -0.33 scores on a scale | Standard Deviation 0.5 |
| Part A: Tezepelumab 2.1 mg SC | Part B: Change From Baseline in Investigator's Global Assessment (IGA) | Day 29 | -0.56 scores on a scale | Standard Deviation 0.73 |
| Part A: Tezepelumab 2.1 mg SC | Part B: Change From Baseline in Investigator's Global Assessment (IGA) | Day 43 | -0.44 scores on a scale | Standard Deviation 0.53 |
| Part A: Tezepelumab 2.1 mg SC | Part B: Change From Baseline in Investigator's Global Assessment (IGA) | Day 57 | -0.44 scores on a scale | Standard Deviation 0.73 |
| Part A: Tezepelumab 2.1 mg SC | Part B: Change From Baseline in Investigator's Global Assessment (IGA) | Day 85 | -0.63 scores on a scale | Standard Deviation 0.74 |
| Part A: Tezepelumab 2.1 mg SC | Part B: Change From Baseline in Investigator's Global Assessment (IGA) | Day 113 | -0.44 scores on a scale | Standard Deviation 0.73 |
| Part A: Tezepelumab 7 mg SC | Part B: Change From Baseline in Investigator's Global Assessment (IGA) | Day 85 | -1.33 scores on a scale | Standard Deviation 0.58 |
| Part A: Tezepelumab 7 mg SC | Part B: Change From Baseline in Investigator's Global Assessment (IGA) | Day 15 | 0.33 scores on a scale | Standard Deviation 0.58 |
| Part A: Tezepelumab 7 mg SC | Part B: Change From Baseline in Investigator's Global Assessment (IGA) | Day 57 | -1.00 scores on a scale | Standard Deviation 0 |
| Part A: Tezepelumab 7 mg SC | Part B: Change From Baseline in Investigator's Global Assessment (IGA) | Day 29 | -0.67 scores on a scale | Standard Deviation 0.58 |
| Part A: Tezepelumab 7 mg SC | Part B: Change From Baseline in Investigator's Global Assessment (IGA) | Day 113 | -0.33 scores on a scale | Standard Deviation 1.15 |
| Part A: Tezepelumab 7 mg SC | Part B: Change From Baseline in Investigator's Global Assessment (IGA) | Day 43 | -1.00 scores on a scale | Standard Deviation 0 |
Secondary
Part B: Elimination Half-life (t1/2) of Tezepelumab
Elimination half-life was estimated based on the serum concentrations of tezepelumab using noncompartmental methods based on the terminal phase of the concentration-time profile. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.
Time frame: Day 1 predose, 0.25, 0.5, 1, 4, 8, 72 hours postdose and days, 7, 15, 22, 29, 43, 57, 71, 85, and 113.
Population: Participants in Part B who received tezepelumab and had a sufficient number of serum concentration measurements for computing the PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Tezepelumab 2.1 mg SC | Part B: Elimination Half-life (t1/2) of Tezepelumab | 22.2 days | Standard Deviation 4.72 |
Secondary
Part B: Maximum Observed Concentration (Cmax) of Tezepelumab
Cmax was estimated based on the serum concentrations of tezepelumab using noncompartmental methods. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.
Time frame: Day 1 predose, 0.25, 0.5, 1, 4, 8, 72 hours postdose and days, 7, 15, 22, 29, 43, 57, 71, 85, and 113.
Population: Participants in Part B who received tezepelumab and had a sufficient number of serum concentration measurements for computing the PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Tezepelumab 2.1 mg SC | Part B: Maximum Observed Concentration (Cmax) of Tezepelumab | 253 μg/mL | Standard Deviation 57.2 |
Secondary
Part B: Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Eczema Area and Severity Index (EASI 50) Score
EASI is a tool used to measure the severity of AD. The index involves an assessment of the average intensity of 4 clinical signs (erythema, infiltration/papulation, excoriations, and lichenification) at 4 body areas (head/neck, upper extremities, trunk, lower extremities) assessed on a scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe. The percent of affected area for each of the 4 body areas is also assessed using the following 6-point scale: 0 = 0%, 1 = \< 10%, 2 =10% to 29%, 3 = 30% to 49%, 4 = 50% to 69%, 5 = 70% to 89%, 6 = 90% to 100%. The total score for each body region is obtained by multiplying the sum of the severity scores of the 4 clinical signs by the area score, with adjustment for the proportion of the body region to the whole body. The sum of the scores for each body region gives the total EASI score, which ranges from 0 to 72, with higher scores indicating greater disease severity.
Time frame: Baseline and days 15, 29, 43, 57, 85, and 113
Population: All participants in Part B who received at least 1 dose of study drug and with available data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Tezepelumab 2.1 mg SC | Part B: Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Eczema Area and Severity Index (EASI 50) Score | Day 15 | 22 percentage of participants |
| Part A: Tezepelumab 2.1 mg SC | Part B: Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Eczema Area and Severity Index (EASI 50) Score | Day 85 | 50 percentage of participants |
| Part A: Tezepelumab 2.1 mg SC | Part B: Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Eczema Area and Severity Index (EASI 50) Score | Day 29 | 22 percentage of participants |
| Part A: Tezepelumab 2.1 mg SC | Part B: Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Eczema Area and Severity Index (EASI 50) Score | Day 113 | 33 percentage of participants |
| Part A: Tezepelumab 2.1 mg SC | Part B: Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Eczema Area and Severity Index (EASI 50) Score | Day 57 | 22 percentage of participants |
| Part A: Tezepelumab 2.1 mg SC | Part B: Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Eczema Area and Severity Index (EASI 50) Score | At any postdose time point | 56 percentage of participants |
| Part A: Tezepelumab 2.1 mg SC | Part B: Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Eczema Area and Severity Index (EASI 50) Score | Day 43 | 22 percentage of participants |
| Part A: Tezepelumab 7 mg SC | Part B: Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Eczema Area and Severity Index (EASI 50) Score | At any postdose time point | 33 percentage of participants |
| Part A: Tezepelumab 7 mg SC | Part B: Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Eczema Area and Severity Index (EASI 50) Score | Day 15 | 0 percentage of participants |
| Part A: Tezepelumab 7 mg SC | Part B: Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Eczema Area and Severity Index (EASI 50) Score | Day 29 | 0 percentage of participants |
| Part A: Tezepelumab 7 mg SC | Part B: Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Eczema Area and Severity Index (EASI 50) Score | Day 43 | 33 percentage of participants |
| Part A: Tezepelumab 7 mg SC | Part B: Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Eczema Area and Severity Index (EASI 50) Score | Day 57 | 0 percentage of participants |
| Part A: Tezepelumab 7 mg SC | Part B: Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Eczema Area and Severity Index (EASI 50) Score | Day 85 | 0 percentage of participants |
| Part A: Tezepelumab 7 mg SC | Part B: Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Eczema Area and Severity Index (EASI 50) Score | Day 113 | 33 percentage of participants |
Secondary
Part B: Percentage of Participants Achieving at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) Score
EASI is a tool used to measure the severity of AD. The index involves an assessment of the average intensity of 4 clinical signs (erythema, infiltration/papulation, excoriations, and lichenification) at 4 body areas (head/neck, upper extremities, trunk, lower extremities) assessed on a scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe. The percent of affected area for each of the 4 body areas is also assessed using the following 6-point scale: 0 = 0%, 1 = \< 10%, 2 =10% to 29%, 3 = 30% to 49%, 4 = 50% to 69%, 5 = 70% to 89%, 6 = 90% to 100%. The total score for each body region is obtained by multiplying the sum of the severity scores of the 4 clinical signs by the area score, with adjustment for the proportion of the body region to the whole body. The sum of the scores for each body region gives the total EASI score, which ranges from 0 to 72, with higher scores indicating greater disease severity.
Time frame: Baseline and days 15, 29, 43, 57, 85, and 113
Population: All participants in Part B who received at least 1 dose of study drug and with available data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Tezepelumab 2.1 mg SC | Part B: Percentage of Participants Achieving at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) Score | Day 57 | 11 percentage of participants |
| Part A: Tezepelumab 2.1 mg SC | Part B: Percentage of Participants Achieving at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) Score | Day 85 | 13 percentage of participants |
| Part A: Tezepelumab 2.1 mg SC | Part B: Percentage of Participants Achieving at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) Score | Day 15 | 0 percentage of participants |
| Part A: Tezepelumab 2.1 mg SC | Part B: Percentage of Participants Achieving at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) Score | Day 113 | 22 percentage of participants |
| Part A: Tezepelumab 2.1 mg SC | Part B: Percentage of Participants Achieving at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) Score | Day 43 | 0 percentage of participants |
| Part A: Tezepelumab 2.1 mg SC | Part B: Percentage of Participants Achieving at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) Score | At any postdose time point | 22 percentage of participants |
| Part A: Tezepelumab 2.1 mg SC | Part B: Percentage of Participants Achieving at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) Score | Day 29 | 0 percentage of participants |
| Part A: Tezepelumab 7 mg SC | Part B: Percentage of Participants Achieving at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) Score | At any postdose time point | 0 percentage of participants |
| Part A: Tezepelumab 7 mg SC | Part B: Percentage of Participants Achieving at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) Score | Day 15 | 0 percentage of participants |
| Part A: Tezepelumab 7 mg SC | Part B: Percentage of Participants Achieving at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) Score | Day 29 | 0 percentage of participants |
| Part A: Tezepelumab 7 mg SC | Part B: Percentage of Participants Achieving at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) Score | Day 43 | 0 percentage of participants |
| Part A: Tezepelumab 7 mg SC | Part B: Percentage of Participants Achieving at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) Score | Day 85 | 0 percentage of participants |
| Part A: Tezepelumab 7 mg SC | Part B: Percentage of Participants Achieving at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) Score | Day 113 | 0 percentage of participants |
| Part A: Tezepelumab 7 mg SC | Part B: Percentage of Participants Achieving at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) Score | Day 57 | 0 percentage of participants |
Secondary
Part B: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score
EASI is a tool used to measure the severity of AD. The index involves an assessment of the intensity of 4 clinical signs (erythema, infiltration/papulation, excoriations, and lichenification) at 4 body areas (head/neck, upper extremities, trunk, lower extremities) assessed on a scale from 0 (none) to 3 (severe). The percent affected area for each of the 4 body areas is assessed on a 6-point scale from 0 (0%) to 6 (90% to 100%). The total score for each body region is obtained by multiplying the sum of the severity scores of the 4 clinical signs by the area score, with adjustment for the proportion of the body region to the whole body. The total EASI score is the sum of the scores for each body region, and ranges from 0 to 72, with higher scores indicating greater disease severity. Percent change from baseline = \[(Post-baseline Value - Baseline Value) / Baseline Value\] x 100. A negative change from baseline indicates improvement.
Time frame: Baseline and days 15, 29, 43, 57, 85, and 113
Population: All participants in Part B who received at least 1 dose of study drug and with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Tezepelumab 2.1 mg SC | Part B: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score | Day 15 | -12.47 percent change | Standard Deviation 43.32 |
| Part A: Tezepelumab 2.1 mg SC | Part B: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score | Day 29 | -23.61 percent change | Standard Deviation 32.82 |
| Part A: Tezepelumab 2.1 mg SC | Part B: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score | Day 43 | -17.04 percent change | Standard Deviation 44.28 |
| Part A: Tezepelumab 2.1 mg SC | Part B: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score | Day 57 | -22.83 percent change | Standard Deviation 41.23 |
| Part A: Tezepelumab 2.1 mg SC | Part B: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score | Day 85 | -31.70 percent change | Standard Deviation 42.14 |
| Part A: Tezepelumab 2.1 mg SC | Part B: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score | Day 113 | -25.25 percent change | Standard Deviation 49.4 |
| Part A: Tezepelumab 7 mg SC | Part B: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score | Day 85 | -23.01 percent change | Standard Deviation 21.16 |
| Part A: Tezepelumab 7 mg SC | Part B: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score | Day 15 | 15.10 percent change | Standard Deviation 55.84 |
| Part A: Tezepelumab 7 mg SC | Part B: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score | Day 57 | -1.89 percent change | Standard Deviation 37.24 |
| Part A: Tezepelumab 7 mg SC | Part B: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score | Day 29 | -25.03 percent change | Standard Deviation 20.38 |
| Part A: Tezepelumab 7 mg SC | Part B: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score | Day 113 | -11.28 percent change | Standard Deviation 54.63 |
| Part A: Tezepelumab 7 mg SC | Part B: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score | Day 43 | -32.41 percent change | Standard Deviation 31.81 |
Secondary
Part B: Time of Maximum Observed Concentration (Tmax) of Tezepelumab
Tmax was estimated based on the serum concentrations of tezepelumab using noncompartmental methods. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.
Time frame: Day 1 predose, 0.25, 0.5, 1, 4, 8, 72 hours postdose and days, 7, 15, 22, 29, 43, 57, 71, 85, and 113.
Population: Participants in Part B who received tezepelumab and had a sufficient number of serum concentration measurements for computing the PK parameter.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Tezepelumab 2.1 mg SC | Part B: Time of Maximum Observed Concentration (Tmax) of Tezepelumab | 4.08 hours |