Safety Study of Tezepelumab (AMG 157) in Healthy Adults and Adults With Atopic Dermatitis
Condition: Atopic Dermatitis; Healthy Volunteers
MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema
Intervention: Tezepelumab; Placebo
Intervention description: Administered by subcutaneous or intravenous injection; Matching placebo administered by subcutaneous or intravenous injection.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
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.
Masking: Double (Participant, Investigator)
Enrollment: 78.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: atopic dermatitis; skin diseases; healthy volunteer

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.