NCT04570657

Brief Summary

Study D9181C00001 is a Phase II, randomised, double-blind, placebo-controlled, parallel group, proof of concept study to evaluate the efficacy, safety, pharmacokinetics (PK) and immunogenicity of MEDI3506 in adult participants with uncontrolled moderate to severe asthma on standard of care (SOC). Up to approximately 80 sites globally will participate in this study. Approximately 228 participants will be randomized to 3 treatment groups in a 1:1:1 ratio to receive MEDI3506 dose 1, MEDI3506 dose 2, or placebo.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
250

participants targeted

Target at P75+ for phase_2 asthma

Timeline
Completed

Started Sep 2020

Typical duration for phase_2 asthma

Geographic Reach
7 countries

65 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 7, 2020

Completed
1 month until next milestone

Study Start

First participant enrolled

September 17, 2020

Completed
13 days until next milestone

First Posted

Study publicly available on registry

September 30, 2020

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 12, 2022

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 6, 2023

Completed
12 months until next milestone

Results Posted

Study results publicly available

January 30, 2024

Completed
Last Updated

January 30, 2024

Status Verified

January 1, 2024

Enrollment Period

2.2 years

First QC Date

August 7, 2020

Results QC Date

December 12, 2023

Last Update Submit

January 9, 2024

Conditions

Keywords

MEDI3506lung functionIL-33inflammation

Outcome Measures

Primary Outcomes (1)

  • Change From Baseline to Week 16 in Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in the First Second (FEV1) as Measured in the Study Clinic

    In-clinic spirometry measurements were taken prior to the administration of bronchodilators. Baseline was the last measurement prior to first injection of investigational product (IP). The least squares (LS) means, LS mean differences and 80% confidence intervals (CIs), and one-sided p-value results were based on a mixed model repeated measures (MMRM). The model included fixed effects for baseline, background medication, geographic region, baseline inhaled corticosteroids (ICS) total daily dose, visit, treatment, and the baseline by visit and treatment by visit interactions. Visits within participant were considered as repeated measurements.

    Baseline and week 16

Secondary Outcomes (11)

  • Change From Baseline to Weeks 8 and 16 in Post-bronchodilator (Post-BD) FEV1 as Measured in the Study Clinic

    Baseline and weeks 8 and 16

  • Serum Concentrations of Tozorakimab

    Pharmacokinetic (PK) samples were taken pre-dose (day 1) and at weeks 1, 4, 8, 12, 16, 20, and 24

  • Number of Participants With Anti-drug Antibodies (ADAs)

    Blood samples were taken pre-dose (day 1) and at weeks 1, 4, 8, 12, 16, and 24

  • Change From Baseline to Week 16 in the Asthma Control Questionnaire-6 (ACQ-6) Score

    Baseline and week 16

  • Number of Participants With a Decrease in ACQ-6 Score ≥ 0.5 From Baseline to Week 16

    Baseline and week 16

  • +6 more secondary outcomes

Other Outcomes (2)

  • Change From Baseline to Week 16 in Pre-BD FEV1 as Measured in the Study Clinic: Analysis Per Number of Exacerbations in Last 12 Months

    Baseline and week 16

  • Eosinophil Count

    Baseline and Week 16

Study Arms (3)

MEDI3506 Dose 1

EXPERIMENTAL

Approximately 76 participants will be randomized to this arm to receive the higher dose of MEDI3506

Biological: MEDI3506

MEDI3506 Dose 2

EXPERIMENTAL

Approximately 76 participants will be randomized to this arm to receive the lower dose of MEDI3506

Biological: MEDI3506

Placebo

PLACEBO COMPARATOR

Approximately 76 participants will be randomized to this arm. Participants in this group will receive the placebo.

Drug: Placebo

Interventions

MEDI3506BIOLOGICAL

Participants will receive multiple doses of MEDI3506 at dose level 1 or dose level 2

MEDI3506 Dose 1MEDI3506 Dose 2

Participants will receive multiple doses of placebo

Placebo

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Aged 18 to \< 65 years of age
  • Physician-diagnosed asthma of early onset, defined as development of asthma before the age of 25 years.
  • History of ≥ 1 asthma exacerbation in previous 24 months
  • Treated with medium to high dose ICS defined as total daily dose of \> 250 g fluticasone dry powder or equivalent, for at least 12 months and on a stable dose for ≥ 3 months.
  • Stable LABA therapy for ≥ 3 months.
  • An ACQ-6 score ≥ 1.5.
  • Morning pre-BD FEV1 ≥ 40% predicted normal and \> 1 L.
  • Morning pre-BD FEV1 \< 85% predicted normal.
  • Participants with documented evidence of asthma as demonstrated by either:
  • BD reversibility, within 12 months, or at screening, or
  • Positive methacholine challenge test within 12 months.
  • Bodyweight ≥ 40 kg and BMI \< 40 kg/m2.
  • For female participants, a negative pregnancy test.
  • Abide by contraception requirements for males and females
  • Provide informed consent

You may not qualify if:

  • Participants with a positive diagnostic nucleic acid test for SARS-CoV-2.
  • Participants with a significant COVID-19 illness within 6 months of enrolment:
  • Participants with a recent history of, or who have a positive test for, infective hepatitis or unexplained jaundice, or participants who have been treated for hepatitis B, hepatitis C, or HIV.
  • Evidence of active or latent TB:
  • An LVEF \< 45% measured by echocardiogram during screening.
  • A family history of heart failure.
  • Current smokers or recent ex-smokers i.e., have quit e cigarettes or other inhaled tobacco products ≤ 6 months prior to SV1.
  • Ex-smokers with a total smoking history of \> 10 pack years.
  • As judged by the investigator, any evidence of any active medical or psychiatric condition or other reason (prior to randomisation) that in the investigator's opinion makes it undesirable for the participant to participate in the study.
  • Any clinically important pulmonary disease other than asthma.
  • Any other clinically relevant abnormal findings on physical examination or laboratory testing, that in the opinion of the investigator or medical monitor might compromise the safety of the participant in the study or interfere with evaluation of the study intervention.
  • A known history of severe reaction to any medication including biologic agents or human gamma globulin therapy.
  • History of, or a reason to believe, a participant has a history of, drug or alcohol abuse within the past 2 years.
  • Current diagnosis of cancer.
  • History of cancer, except if treated with apparent success with curative therapy (response duration of \> 5 years).
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (65)

Research Site

Bakersfield, California, 93301, United States

Location

Research Site

Los Angeles, California, 90025, United States

Location

Research Site

Newport Beach, California, 92663, United States

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Research Site

Coral Gables, Florida, 33134, United States

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Research Site

Ames, Iowa, 50010-3014, United States

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Research Site

Missoula, Montana, 59808, United States

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Research Site

Toledo, Ohio, 43617, United States

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Research Site

Edmond, Oklahoma, 73034, United States

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Research Site

Boerne, Texas, 78006, United States

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Research Site

Buenos Aires, C1121 ABE, Argentina

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Research Site

Buenos Aires, C1414AIF, Argentina

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Research Site

CABA, C1425BEN, Argentina

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Research Site

Córdoba, X5003DCE, Argentina

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Research Site

Florida, B1602DQD, Argentina

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Research Site

Godoy Cruz, 5501, Argentina

Location

Research Site

Lanús Este, B1824KAJ, Argentina

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Research Site

Mar del Plata, 7600, Argentina

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Research Site

Mendoza, 5500, Argentina

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Research Site

Mendoza, M5500GHB, Argentina

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Research Site

Quilmes, B1878FNR, Argentina

Location

Research Site

San Juan Bautista, 1888, Argentina

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Research Site

San Miguel de Tucumán, 4000, Argentina

Location

Research Site

Berlin, 10717, Germany

Location

Research Site

Cottbus, 03050, Germany

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Research Site

Frankfurt, 60596, Germany

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Research Site

Frankfurt am Main, 60389, Germany

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Research Site

Koblenz, 56068, Germany

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Research Site

Landsberg, 86899, Germany

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Leipzig, 04357, Germany

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Research Site

Lübeck, 23552, Germany

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Research Site

Magdeburg, 39120, Germany

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Research Site

Mainz, 55128, Germany

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Research Site

Peine, 31224, Germany

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Research Site

Schwerin, 19055, Germany

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Research Site

Balassagyarmat, 2660, Hungary

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Research Site

Budapest, 1033, Hungary

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Research Site

Gödöllő, 2100, Hungary

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Research Site

Százhalombatta, 2440, Hungary

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Research Site

Szeged, 6722, Hungary

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Research Site

Bialystok, 15-044, Poland

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Research Site

Bychawa, 23100, Poland

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Research Site

Bydgoszcz, 85-231, Poland

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Research Site

Katowice, 40-648, Poland

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Research Site

Krakow, 30-033, Poland

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Research Site

Lodz, 90-302, Poland

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Lublin, 20-362, Poland

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Research Site

Poznan, 60-214, Poland

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Research Site

Tarnów, 33-100, Poland

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Research Site

Wroclaw, 53-301, Poland

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Research Site

Wroclaw, 54-239, Poland

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Research Site

Bellville, 7530, South Africa

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Research Site

Benoni, 1500, South Africa

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Research Site

Bloemfontein, 9301, South Africa

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Research Site

Cape Town, 7500, South Africa

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Research Site

Cape Town, 7572, South Africa

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Research Site

Cape Town, 7700, South Africa

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Research Site

Durban, 4001, South Africa

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Research Site

Durban, 4091, South Africa

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Research Site

Johannesburg, 2113, South Africa

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Research Site

Pretoria, 0002, South Africa

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Research Site

Welkom, 9460, South Africa

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Research Site

Bradford, BD9 6RJ, United Kingdom

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Research Site

Cambridge, CB2 0QQ, United Kingdom

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Research Site

High Wycombe, HP11 2QW, United Kingdom

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Research Site

London, W1T 6AH, United Kingdom

Location

Related Links

MeSH Terms

Conditions

AsthmaInflammation

Condition Hierarchy (Ancestors)

Bronchial DiseasesRespiratory Tract DiseasesLung Diseases, ObstructiveLung DiseasesRespiratory HypersensitivityHypersensitivity, ImmediateHypersensitivityImmune System DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Limitations and Caveats

15 participants enrolled at 1 study centre were excluded from the final analysis due to inability to confirm the validity of the data reported by the site. The exclusion of data from this site did not change the interpretation of the primary endpoint, or results in a significant change to the interpretation of any other endpoint.

Results Point of Contact

Title
Global Clinical Lead
Organization
AstraZeneca AB

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 7, 2020

First Posted

September 30, 2020

Study Start

September 17, 2020

Primary Completion

December 12, 2022

Study Completion

February 6, 2023

Last Updated

January 30, 2024

Results First Posted

January 30, 2024

Record last verified: 2024-01

Data Sharing

IPD Sharing
Will share

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
More information

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