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A Dose Ranging Placebo-Controlled Double-Blind Study to Evaluate the Safety and Efficacy of Tezepelumab in Atopic Dermatitis

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ClinicalTrials.gov Identifier: NCT03809663
Recruitment Status : Recruiting
First Posted : January 18, 2019
Last Update Posted : May 23, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE January 10, 2019
First Posted Date  ICMJE January 18, 2019
Last Update Posted Date May 23, 2019
Actual Study Start Date  ICMJE March 15, 2019
Estimated Primary Completion Date March 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 17, 2019)
Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) (IGA 0/1) and 75% reduction of EASI at Week 16 [ Time Frame: Week 16 ]
Evaluate the effect of tezepelumab compared with placebo, assessed using the Investigator's Global Assessment (IGA) and Eczema Area and Severity Index (EASI)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03809663 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2019)
  • 50% and 90% reduction in EASI [ Time Frame: Week 16 ]
    Estimate the effect of tezepelumab compared with placebo on the efficacy measure of EASI
  • Time at which EASI 50/75/90 is achieved from day 1 [ Time Frame: Day 1 ]
    Estimate the time needed to reach EASI 50/75/90
  • SCORAD (Scoring Atopic Dermatitis) at week 16 [ Time Frame: Week 16 ]
    Estimate the effect of tezepelumab compared with placebo on the efficacy measure of Scoring Atopic Dermatitis (SCORAD). The scale is used to assess the severity (extent, intensity) of Atopic Dermatitis including lesions and subjective symptoms. The minimum score is 0 (zero) and maximum score is 103. Therefore, the scale represented would be 0-103 with higher values indicating more severe disease.
  • Pruritus NRS (Numerical Rating Scale) at week 16 [ Time Frame: Week 16 ]
    Estimate the effect of tezepelumab compared with placebo on the patient-reported outcome (PRO) measure of pruritus assessed using an numeric rating scale (NRS). Scale is 0 (zero) to 10, where 0 represents no itch and 10 represents worst imaginable itch.
  • Serum trough concentrations of tezepelumab at scheduled visits [ Time Frame: Up to week 70 ]
    Characterize the pharmacokinetics (PK) of tezepelumab
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: January 17, 2019)
Subject incidence of adverse events [ Time Frame: Day 1 ]
Establish the safety and tolerability of tezepelumab compared with placebo
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A Dose Ranging Placebo-Controlled Double-Blind Study to Evaluate the Safety and Efficacy of Tezepelumab in Atopic Dermatitis
Official Title  ICMJE A Dose-Ranging, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Tezepelumab Alone or Combined With Topical Corticosteroids in Moderate-to-Severe Atopic Dermatitis
Brief Summary This phase 2b study is designed to evaluate the safety and efficacy of tezepelumab as a monotherapy and explore its efficacy as adjunct therapy in subjects with moderate-to-severe AD.
Detailed Description

All subjects will receive a SC dose of either investigational product or placebo as the first dose on day 1.

Subjects who are determined to be non-responders in Part A will receive tezepelumab SC Q2W following completion of all week 16 study activities. Nonresponders are defined as those subjects who have not achieved at least a 50% improvement in EASI at week 16 compared to baseline (day 1).

Safety follow-up is 12 weeks after the EOT visit (14 weeks after the final dose of investigational product).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
This phase 2b study is designed to evaluate the safety and efficacy of tezepelumab as a monotherapy and explore its efficacy as adjunct therapy in subjects with moderate-to-severe AD. This study consists of Part A (the main study evaluating tezepelumab as a monotherapy) and Part B (a study evaluating tezepelumab as adjunctive therapy when combined with a topical corticosteroid regimen
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Atopic Dermatitis
Intervention  ICMJE
  • Drug: Tezepelumab
    Solution for injection
    Other Name: AMG157
  • Other: Placebo
    Placebo solution for injection
Study Arms  ICMJE
  • Experimental: Tezepelumab high dose
    subcutaneous injection every 2 weeks
    Interventions:
    • Drug: Tezepelumab
    • Other: Placebo
  • Experimental: Tezepelumab low dose
    subcutaneous injection every 4 weeks
    Interventions:
    • Drug: Tezepelumab
    • Other: Placebo
  • Experimental: Tezepelumab medium dose
    subcutaneous injection every 2 weeks
    Interventions:
    • Drug: Tezepelumab
    • Other: Placebo
  • Placebo Comparator: Placebo
    subcutaneous injection every 2 weeks or every 4 weeks
    Interventions:
    • Drug: Tezepelumab
    • Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 17, 2019)
300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 17, 2021
Estimated Primary Completion Date March 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subject has provided informed consent prior to initiation of any study specific activities/procedures.
  • Age greater than or equal to 18 to less than or equal to 75 years at screening.
  • Clinical diagnosis of chronic AD (also known as atopic eczema) for at least 2 years prior to screening and has confirmed AD (Hanifin and Rajka criteria for AD (Hanifin and Rajka, 1980).
  • AD that affects greater than or equal to' 10% body surface area as assessed by EASI at screening and on day 1.
  • An IGA score of greater than or equal to 3 at screening and on day 1.
  • An EASI score of greater than or equal to 16 at screening and on day 1.
  • Subject discontinued treatment with TCS, topical calcineurin inhibitors (TCI), prescription moisturizers, or moisturizers containing additives such as ceramide, hyaluronic acid, urea, or filaggrin for at least the 7 days immediately prior to the first dose of investigational product.
  • Documented recent history (within 12 months before the screening visit) of inadequate response totreatment with topical TCS or subjects for whom topical treatments are otherwise medically inadvisable (ie, because of important side effects or safety risks).
  • Inadequate response is defined as failure to achieve and maintain remission or a low disease activity state (comparable to IGA 0 = clear to IGA 2 = mild) despite treatment with a daily regimen of TCS of medium or higher potency (with or without TCI as appropriate).

Exclusion Criteria:

  • Active dermatologic conditions, which might confound the diagnosis of AD or would interfere with the assessment of treatment, such as scabies, seborrheic dermatitis, cutaneous lymphoma, ichthyosis, psoriasis, allergic contact dermatitis, or irritant contact dermatitis.
  • History of a clinically significant infection within 28 days prior to day 1 that, in the opinion of the investigator or medical monitor, might compromise the safety of the subject in the study, interfere with evaluation of the investigational product, or reduce the subject's ability to participate in the study. Clinically significant infections are defined as either of the following: 1) a systemic infection; or 2) a serious skin infection requiring parenteral antibiotic, antiviral, or antifungal medication.
  • Diagnosis of a helminth parasitic infection within 6 months prior to screening that had not been treated with or had failed to respond to standard of care therapy.
  • Documented medical history of chronic alcohol or drug abuse within 12 months prior to screening.
  • History of anaphylaxis following any biologic therapy.
  • Evidence of active liver disease at screening, including jaundice or aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase greater than twice the upper limit of normal (ULN).
  • Diagnosis and/or treatment of tuberculosis within the 12 months prior to screening.
  • Positive hepatitis B surface antigen or hepatitis C antibody serology. Subjects with a history of hepatitis B vaccination without a history of hepatitis B are allowed to enroll in the study.
  • Positive human immunodeficiency virus (HIV) test at screening or the subject is taking antiretroviral medications, as determined by medical history, prior medications, and/or the subject's verbal report.
  • Other Medical Conditions>
  • History of malignancy, except for basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy ≥ 12 months prior to screening or other malignancies treated with apparent success with curative therapy ≥ 5 years prior to screening.
  • History or evidence of severe depression, schizophrenia, previous suicide attempts, or suicidal ideation.

Prior/Concomitant Therapy:

  • Subjects who are unwilling to abstain from the use of TCS, TCI, prescription moisturizers, or moisturizers containing additives such as ceramide, hyaluronic acid, urea, or filaggrin from screening through week 16 (applies only to Part A subjects)
  • Subjects who have had side effects of topical medications including intolerance to treatment, hypersensitivity reactions, significant skin atrophy, or systemic effects as assessed by the investigator or by the subject's treating physician (applies only to Part B subjects)
  • More than or equal to 30% of the total lesional surface is located on areas of thin skin that cannot be safely treated with medium or higher potency TCS (eg, face, neck, intertriginous areas, areas of skin atrophy) (applies only to Part B subjects)
  • Receipt of any approved biologic agent (eg, dupilumab) within 4 months prior to screening
  • Have used immunosuppressive/immunomodulating drugs (eg, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, interferon (IFN)-gamma, Janus kinase inhibitors, azathioprine, methotrexate) within 4 weeks prior to screening, or any condition that, in the opinion of the investigator, is likely to require such treatment(s) during the first 4 weeks of study treatment.
  • Have had phototherapy for AD in the 2 months prior to day 1, and subjects unwilling to avoid phototherapy during the first 16 weeks of the study
  • If on allergen-specific immunotherapy, subjects must be on a maintenance dose and schedule for ≥ 28 days prior to screening. Allergen-specific immunotherapy is defined as SC immunotherapy to aeroallergens and/o venom (Hymenoptera) as well as sublingual immunotherapy to aeroallergens
  • Vaccination with a live or attenuated vaccine within 28 days prior to day 1. Receipt of inactive/killed vaccinations (eg, inactive influenza) is allowed, provided the vaccinations are not administered within 7 days before or after any study visit. Note that receipt of the Th2 cytokine inhibitor suplatast within 15 days prior to screening is allowed.
  • Major surgery within 8 weeks prior to screening or planned inpatient surgery or hospitalization during the study period
  • Currently receiving treatment in another investigational device or drug study, or less than 6 months since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.

Other Exclusions:

  • Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 14 weeks after the last dose of investigational product. (Females of childbearing potential should only be enrolled in the study after a negative highly sensitive serum pregnancy test).
  • Female subjects of childbearing potential who are sexually active with unsterilized male partners unwilling to use 1 highly effective method of contraception during treatment and for an additional 14 weeks after the last dose of investigational product. Cessation of contraception after this point must be discussed with a responsible physician. Females of childbearing potential are defined as those who are not surgically sterile (ie, had bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause). A highly effective method of contraception is defined as one that resulted in a low failure rate (ie, < 1% per year) when used consistently and correctly. Refer to Appendix 5 for additional contraceptive information.
  • Male subjects with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 14 weeks after the last dose of investigational product. Refer to Appendix 5 for additional contraceptive information.
  • Male subjects with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional 14 weeks after the last dose of investigational product.
  • Male subjects unwilling to abstain from donating sperm during treatment and for an additional 14 weeks after the last dose of investigational product.
  • Subject has known sensitivity to any of the products or components to be administered during dosing.
  • History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com
Listed Location Countries  ICMJE Australia,   Canada,   Czechia,   Estonia,   Japan,   Latvia,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03809663
Other Study ID Numbers  ICMJE 20170755
2018-001997-52 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
URL: https://www.amgen.com/datasharing
Responsible Party Amgen
Study Sponsor  ICMJE Amgen
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP