E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Uncontrolled moderate-to-severe asthma |
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E.1.1.1 | Medical condition in easily understood language |
Uncontrolled moderate-to-severe asthma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effect of MEDI3506 compared with placebo on lung function, in adult participants with uncontrolled moderate-to-severe asthma. |
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E.2.2 | Secondary objectives of the trial |
1. The pharmacokinetics (PK) of MEDI3506 in adult participants with uncontrolled moderate-to-severe asthma. 2. The immunogenicity of MEDI3506 in adult participants with uncontrolled moderate-to-severe asthma. 3. The effect of MEDI3506 compared with placebo on asthma control in adult participants with uncontrolled moderate-to-severe asthma. 4. The effect of MEDI3506 compared with placebo on health status in adult participants with uncontrolled moderate-to-severe asthma. 5. To further assess the effect of MEDI3506 compared with placebo on lung function, in adult participants with uncontrolled moderate-to-severe asthma. 6. The effect of MEDI3506 compared with placebo on composite endpoint for severe exacerbations of asthma (CompEx) in adult participants with uncontrolled moderate-to-severe asthma. 7. The effect of MEDI3506 compared with placebo on concentration of fractional exhaled nitric oxide (FeNO) in adult participants with uncontrolled moderate-to-severe asthma. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Exploratory measures of airway function and structure. |
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E.3 | Principal inclusion criteria |
• Aged 18 to < 65 years of age inclusive. • History of ≥ 1 asthma exacerbation in previous 12 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 < 35 kg/m2. • For female participants, a negative pregnancy test. • Abide by contraception requirements for males and females • Provide informed consent |
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E.4 | Principal 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; • NT-proBNP level greater than the upper limit of the laboratory reference range during screening. • 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The effect of MEDI3506 compared with placebo on lung function, as measured in clinic, change from baseline to Week 16 in pre-BD FEV1 (L). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Serum MEDI3506 concentration-time profiles during the intervention and follow-up periods. 2. Anti-drug antibody during the intervention and follow-up periods. 3. Change from baseline to Week 16 in asthma control questionnaire-6 (ACQ-6) score. Proportion of participants with a decrease in ACQ-6 score of ≥ 0.5 from baseline to Week 16. Proportion of participants achieving ACQ-6 well controlled status (defined as ACQ-6 score ≤ 0.75 at Week 16). 4. Change from baseline to Week 16 in St George’s respiratory questionnaire score (SGRQ). Proportion of participants with a decrease in SGRQ total score of ≥ 4 points from baseline to Week 16. 5. The effect of MEDI3506 compared with placebo on lung function as measured in clinic, change from baseline to Weeks 8 and 16 in post-BD FEV1 (L). 6. Time to first CompEx event based on the period from baseline to Week 16. CompEx annualised event rate. 7. Percent change from baseline to Week 16 in concentration of FeNO in exhaled breath. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Serum MEDI3506 concentration - During the intervention and follow-up periods 2. Anti-drug antibody - During the intervention and follow-up periods 3. ACQ-6 - Week 16 4. SGRQ - Week 16 5. FEV1 - Week 8 and Week 16 6. CompEx - Week 16 7. FeNO - Week 16 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Germany |
Hungary |
Poland |
South Africa |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |