Safety Study of Tezepelumab (AMG 157) in Healthy Adults and Adults With Atopic Dermatitis

NCT00757042 | Completed Phase 1 Results

• 1 other identifier: 20070620
• Study Type: interventional
• Target: 78
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Atopic Dermatitis; Healthy Volunteers

Keywords

atopic dermatitis; skin diseases; healthy volunteer

Outcome Measures

Primary Outcomes (2)

• 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.

  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

• 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.

  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 (14)

• 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.

• 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.

• 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.

• 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.

• 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.

Study Arms (2)

Tezepelumab

EXPERIMENTAL

Participants will receive a single dose of tezepelumab administered subcutaneously or intravenously. The starting dose will be 2.1 mg tezepelumab.

Drug: Tezepelumab

Placebo

PLACEBO COMPARATOR

Participants will receive matching placebo administered subcutaneously or intravenously.

Drug: Placebo

Interventions

Tezepelumab DRUG

Administered by subcutaneous or intravenous injection

Also known as: AMG 157, Tezspire

Tezepelumab

Placebo DRUG

Matching placebo administered by subcutaneous or intravenous injection.

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Related Publications (1)

• 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.

  PMID: 30779339 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Dermatitis, Atopic; Skin Diseases

Interventions

tezepelumab

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 18, 2008
• First Posted: September 22, 2008
• Study Start: September 18, 2008
• Primary Completion: January 5, 2011
• Study Completion: January 5, 2011
• Last Updated: September 21, 2022
• Results First Posted: July 18, 2022

Record last verified: 2022-09