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 |
To assess the PK of MEDI3506 in adult participants with uncontrolled moderate-to-severe asthma. To assess the immunogenicity of MEDI3506 in adult participants with uncontrolled moderate-to-severe asthma. To assess the effect of MEDI3506 compared with placebo on asthma control in adult participants with uncontrolled moderate-to-severe asthma. To assess the effect of MEDI3506 compared with placebo on health status in adult participants with uncontrolled moderate-to-severe asthma. To assess the effect of MEDI3506 compared with placebo on CompEx in adult participants with uncontrolled moderate-to-severe asthma. To assess the effect of MEDI3506 compared with placebo on concentration of FeNO in adult participants with uncontrolled moderate-to-severe asthma. Refer to the protocol for the full list. |
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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. • Physician-diagnosed asthma of early onset, defined as development of asthma before the age of 25 years. • 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 at SV1, SV2, and SV4 (randomisation). • Morning pre-BD FEV1 < 85% predicted normal at SV1. •≥ 70% adherence (days) to eDiary completion both between SV1 and SV2 and in the 14 days preceding SV4. - An adherent day requires completion of evening and subsequent morning diary between SV1 (evening assessment) and SV2 (morning assessment). • ≥ 70% adherence to background medication as assessed by eDiary entries both between SV1 and SV2 and in the 14 days preceding SV4. • Participants must demonstrate ability to perform acceptable inhaler and spirometry techniques. • Able and willing to comply with the requirements of the protocol including ability to read, write, be fluent in the translated language of all participants facing questionnaires used at site, and use electronic devices eg. eDiary and spirometry. • Bodyweight ≥ 40 kg and BMI < 40 kg/m2. • For female participants of childbearing potential (see Appendix I for definition of childbearing potential): - A negative serum pregnancy test at SV1. - A negative urine pregnancy test at SV2 and prior to administration of study intervention at SV4 (randomisation). • Abide by contraception requirements for males and females • Provide informed consent • Participants with documented evidence of asthma as defined in the protocol. • Documented history of ≥ 1 asthma exacerbation in 24 months prior to SV1 (see Section 8.1.5 for definitions of acceptable documentation and asthma exacerbation). • Morning pre-BD FEV1 ≥ 40% predicted normal and > 1 L at SV1. For the full list of inclusion criteria, please refer to section 5.1 of the protocol. |
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E.4 | Principal exclusion criteria |
• Participants with a positive diagnostic PCR test for SARS-CoV-2, the virus responsible for COVID-19, at SV2, or anytime on or after Day-7 and prior to SV4. • Participants with a significant COVID-19 illness within 6 months of enrolment. • Positive hepatitis C antibody, hepatitis B virus surface antigen, or hepatitis B virus core antibody, at screening; or known to have tested positive for human immunodeficiency virus. • 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.
For the full list of exclusion criteria, please refer to section 5.2 of the protocol. |
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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) |
• As measured in clinic, change from baseline to weeks 8 and 16 in postBD FEV1 (L). Endpoints common to Part A and B 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. Time to first CompEx event based on the period from baseline to Week 16. CompEx annualised event rate. 6. 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 |
From baseline to weeks 8 and 16. 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. CompEx - Week 16 6. 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 | 16 |
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 |
South Africa |
United States |
Poland |
Germany |
Hungary |
United Kingdom |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 26 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 14 |