Clinical trial NCT04570657: Study to Assess the Efficacy and Safety of MEDI3506 in Adults With Uncontrolled Moderate-to-severe Asthma
Official title: A Phase II, Randomised, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of MEDI3506 in Adult Participants With Uncontrolled Moderate-to-severe Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: MEDI3506
lung function
IL-33
inflammation
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2020-09-30
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: INCLUSION CRITERIA

* 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

EXCLUSION CRITERIA

* 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).
* History of allogeneic bone marrow transplant.
* A helminth parasitic infection diagnosed within 6 months prior to SV4 (randomisation) that has not been treated, or has not responded to SOC therapy.
* An asthma exacerbation within 8 weeks.
* Receiving any prohibited concomitant medications or therapies as specified in the protocol:

Known history of allergy or reaction to any component of the study intervention formulation, including hereditary fructose intolerance.

Primary outcomes:
measure: 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
timeFrame: Baseline and week 16
Secondary outcomes:
measure: Change From Baseline to Weeks 8 and 16 in Post-bronchodilator (Post-BD) FEV1 as Measured in the Study Clinic
timeFrame: Baseline and weeks 8 and 16
measure: Serum Concentrations of Tozorakimab
timeFrame: Pharmacokinetic (PK) samples were taken pre-dose (day 1) and at weeks 1, 4, 8, 12, 16, 20, and 24
measure: Number of Participants With Anti-drug Antibodies (ADAs)
timeFrame: Blood samples were taken pre-dose (day 1) and at weeks 1, 4, 8, 12, 16, and 24
measure: Change From Baseline to Week 16 in the Asthma Control Questionnaire-6 (ACQ-6) Score
timeFrame: Baseline and week 16
measure: Number of Participants With a Decrease in ACQ-6 Score ≥ 0.5 From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Number of Participants Achieving ACQ-6 Well Controlled Status at Week 16
timeFrame: Baseline and week 16
measure: Change From Baseline to Week 16 in St George's Respiratory Questionnaire (SGRQ) Domain and Total Scores
timeFrame: Baseline and week 16
measure: Number of Participants With a Decrease in SGRQ Total Score of ≥ 4 Points From Baseline to Week 16
timeFrame: Baseline and week 16
measure: Number of Participants With at Least One Asthma CompEx Event From Baseline to Week 16
timeFrame: Baseline to week 16
measure: Asthma CompEx Annualised Event Rate
timeFrame: Baseline to week 16
measure: Percent Change From Baseline to Week 16 in Concentration of Fractional Exhaled Nitric Oxide (FeNO) in Exhaled Breath
timeFrame: Baseline and week 16
Other outcomes:
measure: 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
timeFrame: Baseline and week 16
measure: Eosinophil Count
timeFrame: Baseline and Week 16
Locations:
city: Bakersfield
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Newport Beach
country: United States
facility: Research Site
state: California
city: Coral Gables
country: United States
facility: Research Site
state: Florida
city: Ames
country: United States
facility: Research Site
state: Iowa
city: Missoula
country: United States
facility: Research Site
state: Montana
city: Toledo
country: United States
facility: Research Site
state: Ohio
city: Edmond
country: United States
facility: Research Site
state: Oklahoma
city: Boerne
country: United States
facility: Research Site
state: Texas
city: Buenos Aires
country: Argentina
facility: Research Site
city: Buenos Aires
country: Argentina
facility: Research Site
city: Caba
country: Argentina
facility: Research Site
city: Cordoba
country: Argentina
facility: Research Site
city: Florencio Varela
country: Argentina
facility: Research Site
city: Florida
country: Argentina
facility: Research Site
city: Godoy Cruz
country: Argentina
facility: Research Site
city: Lanus Este
country: Argentina
facility: Research Site
city: Mar del Plata
country: Argentina
facility: Research Site
city: Mendoza
country: Argentina
facility: Research Site
city: Mendoza
country: Argentina
facility: Research Site
city: Quilmes
country: Argentina
facility: Research Site
city: San Miguel de Tucuman
country: Argentina
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Cottbus
country: Germany
facility: Research Site
city: Frankfurt/Main
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Koblenz
country: Germany
facility: Research Site
city: Landsberg
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Lübeck
country: Germany
facility: Research Site
city: Magdeburg
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: Peine
country: Germany
facility: Research Site
city: Schwerin
country: Germany
facility: Research Site
city: Balassagyarmat
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Gödöllő
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Százhalombatta
country: Hungary
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Bychawa
country: Poland
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Katowice
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Tarnów
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Bellville
country: South Africa
facility: Research Site
city: Benoni
country: South Africa
facility: Research Site
city: Bloemfontein
country: South Africa
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Durban
country: South Africa
facility: Research Site
city: Durban
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
city: Welkom
country: South Africa
facility: Research Site
city: Bradford
country: United Kingdom
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: High Wycombe
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
References: