Clinical trial NCT00757042: Safety Study of Tezepelumab (AMG 157) in Healthy Adults and Adults With Atopic Dermatitis
Official title: A Randomized, Double-Blind, Placebo-Controlled, Ascending Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 157 in Healthy Subjects and Subjects With Moderate to Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Atopic Dermatitis
Healthy Volunteers
Keywords: atopic dermatitis
skin diseases
healthy volunteer
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2008-09-22
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 exclusion criteria are as follows:
* Subject who has concurrent skin disease (eg, acne) of such severity in the study area that it could interfere with study evaluation;
* Subject who has active or recent skin infections (within 7 days of randomization);
* Subject who has received phototherapy (eg, ultraviolet \[UV\] A, UVB) known or suspected to have an effect on AD within 6 weeks prior to randomization;
* Subject who has received corticosteroids by other than topical, inhaled or intranasal delivery within 4 weeks prior to randomization;
* Subject who has been treated with topical calcineurin inhibitors within 14 days prior to randomization;
* Subject who uses any medications that interfere with blood coagulation (eg nonsteroidal anti-inflammatory drugs \[NSAIDs\]) or wound healing within 7 days or 5 half-lives (whichever is longer) prior to enrolling into the study and for the duration of the study.
* Subject who smokes more than 10 cigarettes per day within the 6 months prior to randomization and during the study.

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: 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
measure: Number of Participants Who Developed Anti-tezepelumab Antibodies
timeFrame: 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.
Secondary outcomes:
measure: Part A: Time of Maximum Observed Concentration (Tmax) of Tezepelumab
timeFrame: 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.
measure: Part A: Maximum Observed Concentration (Cmax) of Tezepelumab
timeFrame: 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.
measure: Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tezepelumab
timeFrame: 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.
measure: Part A: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Tezepelumab
timeFrame: 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.
measure: Part A: Elimination Half-life (t1/2) of Tezepelumab
timeFrame: 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.
measure: Part B: Time of Maximum Observed Concentration (Tmax) of Tezepelumab
timeFrame: 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.
measure: Part B: Maximum Observed Concentration (Cmax) of Tezepelumab
timeFrame: 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.
measure: Part B: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tezepelumab
timeFrame: 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.
measure: Part B: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Tezepelumab
timeFrame: 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.
measure: Part B: Elimination Half-life (t1/2) of Tezepelumab
timeFrame: 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.
measure: Part B: Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Eczema Area and Severity Index (EASI 50) Score
timeFrame: Baseline and days 15, 29, 43, 57, 85, and 113
measure: Part B: Percentage of Participants Achieving at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) Score
timeFrame: Baseline and days 15, 29, 43, 57, 85, and 113
measure: Part B: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score
timeFrame: Baseline and days 15, 29, 43, 57, 85, and 113
measure: Part B: Change From Baseline in Investigator's Global Assessment (IGA)
timeFrame: Baseline and days 15, 29, 43, 57, 85, and 113
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Parnes JR, Sullivan JT, Chen L, Dias C. Pharmacokinetics, Safety, and Tolerability of Tezepelumab (AMG 157) in Healthy and Atopic Dermatitis Adult Subjects. Clin Pharmacol Ther. 2019 Aug;106(2):441-449. doi: 10.1002/cpt.1401. Epub 2019 Mar 23.