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

A Phase 1 study testing Tezepelumab in people with Atopic Dermatitis and Healthy Volunteers, run by Amgen.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for: Atopic Dermatitis, Healthy Volunteers
What is being tested?: Tezepelumab
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 78 participants
Where: No sites listed yet
Study dates: 18 Sep 2008to 5 Jan 2011
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

Who cannot join

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

Show all 24Show fewer

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.

About this study

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

Conditions: Atopic Dermatitis, Healthy Volunteers
Being tested: Tezepelumab, Placebo
Keywords: atopic dermatitis, skin diseases, healthy volunteer
Medical subject headings: Dermatitis, Atopic, Skin Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TezepelumabDrug
Also called AMG 157, Tezspire
Administered by subcutaneous or intravenous injection
PlaceboDrug
Matching placebo administered by subcutaneous or intravenous injection.

Study groups in NCT00757042
Study group	Role	What they receive
Tezepelumab	Experimental	Participants will receive a single dose of tezepelumab administered subcutaneously or intravenously. The starting dose will be 2.1 mg tezepelumab. Receives: Drug: Tezepelumab
Placebo	Placebo comparator	Participants will receive matching placebo administered subcutaneously or intravenously. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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 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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: Baseline and days 15, 29, 43, 57, 85, and 113
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.
Measured: Baseline and days 15, 29, 43, 57, 85, and 113
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.
Measured: Baseline and days 15, 29, 43, 57, 85, and 113
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.
Measured: Baseline and days 15, 29, 43, 57, 85, and 113

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Sep 20085 Jan 2011

First posted22 Sep 2008 (estimated)
Study start18 Sep 2008
Primary completion5 Jan 2011
Study completion5 Jan 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Atopic DermatitisStudies of the same condition, open and under way.
More trials run by AmgenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
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 blind
Who is masked: Participant, Investigator
Enrolment: 78 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00757042
Sponsor's protocol ID: 20070620
Status last verified: Sep 2022
First submitted: 18 Sep 2008
Last updated: 21 Sep 2022
Results posted: Yes, on ClinicalTrials.gov

Publications

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.
PubMed 30779339

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
RecruitingObservational study
Blood, Urine, and Tissue Collection for Cutaneous Lymphoma, Eczema, and Atopic Dermatitis Research
Cutaneous T-cell Lymphoma, Sezary Syndrome
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Not yet recruitingPhase 1
A Study of HSK60002 Tablets in Participants With Moderate-to-Severe Atopic Dermatitis
Dermatitis Atopic
RecruitingPhase 3
A Study to Learn About the Study Medicine Called Tilrekimig in People With Moderate-to Severe Eczema
Atopic Dermatitis

All Atopic Dermatitis trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00757042
Acronym / sponsor ID: 20070620
Conditions: Atopic Dermatitis, Healthy Volunteers
Keywords: atopic dermatitis, skin diseases, healthy volunteer
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 78 participants (actual)
Lead sponsor: AmgenIndustry (pharma, biotech, devices)
Study start: 18 Sep 2008 (actual)
Primary completion: 5 Jan 2011 (actual)
Study completion: 5 Jan 2011 (actual)
First posted: 22 Sep 2008 (estimated)
Results: Posted 18 Jul 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Double blind (participant, investigator)
Number of arms: 2
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.

Arm	Type	Receives
Tezepelumab	Experimental	Drug: TezepelumabParticipants will receive a single dose of tezepelumab administered subcutaneously or intravenously. The starting dose will be 2.1 mg tezepelumab.
Placebo	Placebo comparator	Drug: PlaceboParticipants will receive matching placebo administered subcutaneously or intravenously.

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (7 listed)

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

Key exclusion criteria (24 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TezepelumabAlso: AMG 157, TezspireAdministered by subcutaneous or intravenous injection	Drug	Tezepelumab
PlaceboMatching placebo administered by subcutaneous or intravenous injection.	Drug	Placebo

Primary outcome

Number of Participants With Adverse Events
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
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
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.
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.

14 secondary outcomes

Part A: Time of Maximum Observed Concentration (Tmax) of Tezepelumab
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.
Part A: Maximum Observed Concentration (Cmax) of Tezepelumab
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.
Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tezepelumab
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.
Part A: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Tezepelumab
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.
Part A: Elimination Half-life (t1/2) of Tezepelumab
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.
Part B: Time of Maximum Observed Concentration (Tmax) of Tezepelumab
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.
Part B: Maximum Observed Concentration (Cmax) of Tezepelumab
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.
Part B: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tezepelumab
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.
Part B: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Tezepelumab
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.
Part B: Elimination Half-life (t1/2) of Tezepelumab
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.
Part B: Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Eczema Area and Severity Index (EASI 50) Score
Time frame: Baseline and days 15, 29, 43, 57, 85, and 113
Part B: Percentage of Participants Achieving at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) Score
Time frame: Baseline and days 15, 29, 43, 57, 85, and 113
Part B: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score
Time frame: Baseline and days 15, 29, 43, 57, 85, and 113
Part B: Change From Baseline in Investigator's Global Assessment (IGA)
Time frame: Baseline and days 15, 29, 43, 57, 85, and 113

Results and safety

Results posted to the registry on 18 Jul 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A: Tezepelumab 2.1 mg SC	6	6
Part A: Tezepelumab 7 mg SC	6	6
Part A: Tezepelumab 21 mg SC	6	6
Part A: Tezepelumab 70 mg SC	6	6
Part A: Tezepelumab 210 mg SC	6	6
Part A: Tezepelumab 420 mg SC	6	6
Part A: Tezepelumab 210 mg IV	6	6
Part A: Tezepelumab 700 mg IV	6	6
Part A: Placebo	16	15
Part B: Tezepelumab 700 mg IV	10	9
Part B: Placebo IV	4	3

Primary outcome: Number of Participants With Adverse Events

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. Count of participants. Unit: Participants

Measure	Part A: Tezepelumab 2.1 mg SC n = 6	Part A: Tezepelumab 7 mg SC n = 6	Part A: Tezepelumab 21 mg SC n = 6	Part A: Tezepelumab 70 mg SC n = 6	Part A: Tezepelumab 210 mg SC n = 6	Part A: Tezepelumab 420 mg SC n = 6	Part A: Tezepelumab 210 mg IV n = 6	Part A: Tezepelumab 700 mg IV n = 6	Part A: Placebo SC n = 12	Part A: Placebo IV n = 4	Part B: Tezepelumab 700 mg IV n = 9	Part B: Placebo IV n = 3
Any adverse event	3	5	1	6	2	3	4	5	8	3	7	3
Serious adverse event	0	0	0	0	0	0	0	0	0	0	0	1
AE leading to study drug discontinuation	0	0	0	0	0	0	0	0	0	0	0	0
AE leading to discontinuation from study	0	0	0	0	0	0	0	0	0	0	0	0
Fatal adverse event	0	0	0	0	0	0	0	0	0	0	0	0
Treatment-related adverse event	1	0	0	0	2	1	2	0	4	1	3	3

Population analysed: All participants who received at least 1 dose of study drug

Primary outcome: Number of Participants Who Developed Anti-tezepelumab Antibodies

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.. Count of participants. Unit: Participants

Measure	Part A: Tezepelumab 2.1 mg SC n = 6	Part A: Tezepelumab 7 mg SC n = 6	Part A: Tezepelumab 21 mg SC n = 6	Part A: Tezepelumab 70 mg SC n = 6	Part A: Tezepelumab 210 mg SC n = 6	Part A: Tezepelumab 420 mg SC n = 6	Part A: Tezepelumab 210 mg IV n = 6	Part A: Tezepelumab 700 mg IV n = 6	Part A: Placebo n = 15	Part B: Tezepelumab 700 mg IV n = 9	Part B: Placebo IV n = 3
Anti-tezepelumab binding antibodies	0	0	0	0	0	0	0	0	1	0	0
Anti-tezepelumab neutralizing antibodies	0	0	0	0	0	0	0	0	0	0	0

Population analysed: All participants who received at least 1 dose of study drug with a postbaseline result.

14 secondary outcomes are reported in the full results.

Adverse events

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. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A: Tezepelumab 2.1 mg SC	0 of 6 (0%)	3 of 6 (50%)	Not reported
Part A: Tezepelumab 7 mg SC	0 of 6 (0%)	5 of 6 (83.3%)	Not reported
Part A: Tezepelumab 21 mg SC	0 of 6 (0%)	1 of 6 (16.7%)	Not reported
Part A: Tezepelumab 70 mg SC	0 of 6 (0%)	6 of 6 (100%)	Not reported
Part A: Tezepelumab 210 mg SC	0 of 6 (0%)	2 of 6 (33.3%)	Not reported
Part A: Tezepelumab 420 mg SC	0 of 6 (0%)	3 of 6 (50%)	Not reported
Part A: Tezepelumab 210 mg IV	0 of 6 (0%)	4 of 6 (66.7%)	Not reported
Part A: Tezepelumab 700 mg IV	0 of 6 (0%)	5 of 6 (83.3%)	Not reported
Part A: Placebo SC	0 of 12 (0%)	8 of 12 (66.7%)	Not reported
Part A: Placebo IV	0 of 4 (0%)	3 of 4 (75%)	Not reported
Part B: Tezepelumab 700 mg IV	0 of 9 (0%)	7 of 9 (77.8%)	Not reported
Part B: Placebo IV	1 of 3 (33.3%)	3 of 3 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 30779339Parnes 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.
AmgenTrials clinical trials websiteLink provided by the sponsor.

Related trials for Atopic Dermatitis

Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
RecruitingObservational study
Blood, Urine, and Tissue Collection for Cutaneous Lymphoma, Eczema, and Atopic Dermatitis Research
Cutaneous T-cell Lymphoma, Sezary Syndrome
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Not yet recruitingPhase 1
A Study of HSK60002 Tablets in Participants With Moderate-to-Severe Atopic Dermatitis
Dermatitis Atopic
RecruitingPhase 3
A Study to Learn About the Study Medicine Called Tilrekimig in People With Moderate-to Severe Eczema
Atopic Dermatitis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MD study director

Amgen

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tezepelumab in people with Atopic Dermatitis and Healthy Volunteers, run by Amgen.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events (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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00757042, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2022.