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Healthy VolunteersPhase 1NCT00972179

Safety Study of Tezepelumab (AMG 157) in Healthy Adults

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

Completed

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

Official record
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Trial summary

The primary objective is to evaluate the safety, tolerability, and immunogenicity of multiple-dose administration of tezepelumab in healthy adults. Read more about this study

Who is it for?
Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for
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
49 participants
Where
No sites listed yet
Study dates
15 Sep 2009to 9 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 45 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Subjects must sign an Institutional Review Board (IRB) approved informed consent form before any study-specific procedures;
  • Healthy subject, aged between 18 and 45 years, inclusive;
  • Female subject must be of non-reproductive potential (ie, postmenopausal by history - no menses for ≥ 1 year and by follicle-stimulating hormone (FSH) [using local reference ranges]; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy);
  • Male subjects with female partner of childbearing potential who agrees to inform their female partner of their participation in this clinical study and use highly effective methods of birth control during the study. (Highly effective methods of birth control may include abstinence, vasectomy, or a condom with spermicide in combination with either hormonal birth control, intra-uterine device, or barrier methods used by the woman);
  • Male subject who agrees to use birth control for five months after last dose of study medication, male subject who agrees not to donate sperm during the study and for five months after last dose of study medication;
  • Healthy subject with a body mass index (BMI) between 18 and 32 kg/m^2, inclusive at screening;
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  • Subject must have normal or clinically acceptable physical examination and electrocardiogram (ECG) results prior to Day 1 based on the opinion of the investigator;
  • Subject must have normal or clinically acceptable clinical laboratory tests at screening as determined by Amgen and the investigator;
  • Subject must have adequate renal function (defined as creatinine clearance > 80 mL/min using the Cockcroft Gault equation).

Who cannot join

  • Subject who has history or evidence of a clinically significant disorder, condition or disease (including but not limited to cardiopulmonary, oncologic, immunologic, autoimmune, collagen vascular, renal, metabolic, hematologic or psychiatric), 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 (eg, common cold, viral syndrome, flu-like symptoms). Subject who, in the opinion of the investigator, has a high risk of parasitic disease is also excluded;
  • Subject who has known positive tuberculin skin test (if not treated with appropriate chemoprophylaxis) or recent (within six months from randomization) exposure to an individual with active tuberculosis;
  • Subject who has history of malignancy of any type, other than in situ cervical cancer or surgically excised non-melanomatous skin cancers within five years before randomization of the study;
  • Subject who has known type I/II diabetes;
  • Subject who uses nonprescription drugs within 14 days prior to randomization and for the entire duration of the study. All herbal supplements, vitamins, and nutritional supplements taken within the last 30 days prior to dosing on Day 1 (and continued use, if appropriate), must be reviewed and approved by the PI and Amgen Medical Monitor;
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  • Subject who has used any systemic cytotoxic or systemic immunosuppressive medications (other than corticosteroids) within 6 months prior to randomization and for the entire duration of the study or has used any corticosteroid, topical cytotoxic or topical immunosuppressive medications within 30 days or five half-lives (whichever is longer) prior to randomization and for the entire duration of the study;
  • Subject who has previously received any other therapeutic monoclonal antibody;
  • Subject who has previously received any investigational drug (or is currently using an investigational device) within 30 days or five half-lives (whichever is longer) prior to randomization;
  • Subject who has tested positive for drugs and/or alcohol use at screening or before randomization, subject who has consumed alcohol within 48 hours prior to any study visit including screening, and subject with alcohol intake of > 2 drinks/day on average during the study (one drink being equivalent to 12 ounces of regular beer, 8 to 9 ounces of malt liquor, 5 ounces of wine or 1.5 ounces of 80 proof distilled spirits);
  • Female subject who is pregnant or lactating; female subject who is of child-bearing potential;
  • Subject who has donated blood (including blood products) or experienced loss of blood ≥ 500 mL within two months of study screening;
  • Subject who is positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen, or hepatitis C antibodies;
  • Subject who has regularly used nicotine or tobacco containing products (including but not limited to: snuff, chewing tobacco, cigars, cigarettes, pipes, or nicotine patches) during six months before randomization and during the study;
  • Subject who has any other condition that might reduce the chance of obtaining data (eg, known poor compliance) required by the protocol or that might compromise the ability to give truly informed consent.

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled, Ascending Multiple Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AMG 157 in Healthy Subjects

The primary objective is to evaluate the safety, tolerability, and immunogenicity of multiple-dose administration of tezepelumab in healthy adults.

Read the detailed description

This study will follow a randomized, multiple-dose, double-blind, placebo-controlled, sequential dose-escalation study design. The study will consist of five subcutaneous (SC) cohorts and one intravenous (IV) cohort. Each dose cohort is planned to enroll 8 participants, randomized such that 6 participants will receive tezepelumab and 2 will receive placebo (3:1 ratio).

Being tested
Placebo, Tezepelumab
Keywords
healthy volunteers

What participants receive

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

  • PlaceboDrug

    Administered by subcutaneous or intravenous injection.

  • TezepelumabDrug

    Also called AMG 157, Tezspire

    Administered by subcutaneous or intravenous injection

Study groups in NCT00972179
Study groupRoleWhat they receive
TezepelumabExperimentalTezepelumab will be administered subcutaneously (SC) at doses from 35 mg once every 28 days (Q28D) (cohort 1) up to 210 mg once every 7 days (Q7D) (cohort 5) and an intravenous (IV) dose cohort of 700 mg Q28D (cohort 6).
Receives: Drug: Tezepelumab
PlaceboPlacebo comparatorTwo participants in each cohort (cohorts 1 to 6) will receive matching placebo administered subcutaneously (cohorts 1-5) or intravenously (cohort 6), matching the treatment regiment of tezepelumab.
Receives: Drug: Placebo

What is being measured

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

  1. Number of Participants With Treatment-emergent 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: From first dose of study drug up to day 169

  2. Number of Participants Who Developed Anti-tezepelumab Antibodies After Initiation of Treatment

    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: For Q28D groups: Days 28, 56, 85, 113, and 169; For Q14D and Q7D groups: Days 29, 57, 85, 113, 141, and 169

Secondary outcomes (5)
  1. Time of Maximum Observed Concentration (Tmax) of Tezepelumab

    The pharmacokinetic (PK) parameter 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 enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification of the assay was 10 ng/ml.

    Measured: First dose: Day 1 predose, end of infusion (EOI; IV cohort only), 4 hours, 3, 7, 14 (Q14D & Q28D only) and 28 days (Q28D only) postdose. Last Dose: Day 57 (Q28D), Day 71 (Q14D) and Day 78 (Q7D) predose, EOI (IV cohort), 4 hours, 3, 7, 14, 28 days postdose

  2. Maximum Observed Concentration (Cmax) of Tezepelumab

    The PK parameter 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: First dose: Day 1 predose, end of infusion (EOI; IV cohort only), 4 hours, 3, 7, 14 (Q14D & Q28D only) and 28 days (Q28D only) postdose. Last Dose: Day 57 (Q28D), Day 71 (Q14D) and Day 78 (Q7D) predose, EOI (IV cohort), 4 hours, 3, 7, 14, 28 days postdose

  3. Area Under the Concentration-time Curve Over the Dosing Interval (AUCtau) for Tezepelumab

    The PK parameter AUCtau was estimated based on the serum concentrations of tezepelumab using noncompartmental methods.

    The dosing interval (tau) was 28 days, 14 days or 7 days depending on the treatment arm.

    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: First dose: Day 1 predose, end of infusion (EOI; IV cohort only), 4 hours, 3, 7, 14 (Q14D & Q28D only) and 28 days (Q28D only) postdose. Last Dose: Day 57 (Q28D), Day 71 (Q14D) and Day 78 (Q7D) predose, EOI (IV cohort), 4 hours, 3, 7, 14, 28 days postdose

  4. Accumulation Ratio Based on AUCtau

    Accumulation ratio (AR) based on AUCtau was calculated as AUCtau after last dose / AUCtau after first dose, except for the Q7D cohort where AR was calculated as AUCtau after last dose / area under the concentration-time curve from time 0 to time of last measurable concentration (AUC0-t) after first dose.

    Measured: First dose: Day 1 predose, end of infusion (EOI; IV cohort only), 4 hours, 3, 7, 14 (Q14D & Q28D only) and 28 days (Q28D only) postdose. Last Dose: Day 57 (Q28D), Day 71 (Q14D) and Day 78 (Q7D) predose, EOI (IV cohort), 4 hours, 3, 7, 14, 28 days postdose

  5. Accumulation Ratio Based on Cmax

    Accumulation ratio based on Cmax calculated as Cmax after last dose / Cmax after first dose

    Measured: First dose: Day 1 predose, end of infusion (EOI; IV cohort only), 4 hours, 3, 7, 14 (Q14D & Q28D only) and 28 days (Q28D only) postdose. Last Dose: Day 57 (Q28D), Day 71 (Q14D) and Day 78 (Q7D) predose, EOI (IV cohort), 4 hours, 3, 7, 14, 28 days postdose

Timeline

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

  1. First posted4 Sep 2009 (estimated)
  2. Study start15 Sep 2009
  3. Primary completion9 Jan 2011
  4. Study completion9 Jan 2011

Resources

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
The cohorts will enroll sequentially: enrollment to the subsequent cohort (ie, next higher dose) will proceed only after the previous dose is determined to be safe and well tolerated by a blinded review of available safety data conducted on day 43 of the previous cohort. Within each dose cohort, participants will be randomized 3:1 to receive tezepelumab or placebo.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00972179
Sponsor's protocol ID
20080390
Status last verified
Sep 2022
First submitted
3 Sep 2009
Last updated
21 Sep 2022

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tezepelumab in people with 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 9 inclusion and 15 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 23 May 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 Treatment-emergent Adverse Events (time frame: From first dose of study drug up to day 169). 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 NCT00972179, 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.

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