E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 evaluate the efficacy of different doses of amlitelimab compared to placebo in participants with moderate-to-severe, uncontrolled asthma
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E.2.2 | Secondary objectives of the trial |
-Evaluate the effects of amlitelimab (AMB) compared to placebo on lung function as measured by forced expiratory volume in 1 second -Evaluate the effects of AMB : --on Asthma Control Questionnaire 5 --on time to 1st severe exacerbation event --on other spirometry assessments --on fraction of exhaled nitric oxide --compared to placebo on reducing the incidence of “loss of asthma control”events --on time to first LOAC event --on asthma symptoms --on reducing the incidence of severe asthma exacerbations requiring hospitalization or emergency room or urgent care visit -Assess the effect of AMB on bronchodilator therapy -Evaluate the pharmacokinetic of AMB and anti-drug antibodies to AMB in participants with asthma -Evaluate the safety of AMB in participants with asthma -Evaluate the effects of AMB on participant reported outcomes and on Asthma Control Questionnaire 6 and 7 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- The participant must be between the ages of 18 and 75 inclusive at the time of signing the informed consent. - Moderate to severe asthma diagnosed by a physician for ≥ 12 months according to stages 4 and 5 of the Global Initiative for Asthma (GINA ). - Participants on existing therapy with medium to high doses of ICS (≥500 μg fluticasone propionate daily or comparable ICS dose in combination with at least one additional controller (e.g., LABA, LTRA, LAMA, methylxanthines) for at least 3 months. - ≥ 1 severe asthma exacerbation in the past year, with at least one exacerbation during treatment with medium to high doses of ICS (≥ 500 μg fluticasone propionate daily or one dose of ICS comparable). - Participants with pre-BD forced expiratory volume in 1 second (FEV1) > 40% and < 80% of predicted normal at the screening visit. - 5-item ACQ-5 score >1.5 at randomization. - Participants with at least 12% reversibility and 200 mL post-BD FEV after administration of albuterol/salbutamol or levalbuterol/levosalbutamol at screening or documented history of a reversibility test. - Weight ≥40 kg and ≤150 kg at the randomization visit.
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E.4 | Principal exclusion criteria |
- Chronic lung disease other than asthma. - Current or former smoker including active vaping of any products and/or marijuana with cessation within 6 months of screening or history of >10 pack-years. - Participants who experience a deterioration of asthma that results in emergency treatment or hospitalization, or treatment with systemic steroids at any time from month prior to screening. - Suspicion of, or confirmed, coronavirus disease 2019 (COVID-19) infection during the screening period including known history of COVID-19 infection within 4 weeks prior to Screening; mechanical ventilation or extracorporeal membrane oxygenation (ECMO) secondary toCOVID-19 within 3 months prior to Screening; COVID-19 infection who have not yet sufficiently recovered to participate in the procedures of a clinical trial. - Active infection or history of clinically significant infection - Known history of, or suspected, significant current immunosuppression, including history of invasive opportunistic or helminthic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration. - Active or latent TB - A history of malignancy of any type (excluding basal and squamous cell skin cancer and in situ cervical carcinoma that has been excised and cured >3 years prior to baseline). - History of solid organ transplant. - Hepatitis B, C or HIV. - Pregnant or breastfeeding. - History (within last 2 years prior to Baseline) of prescription drug or substance abuse, including alcohol, considered significant by the Investigator. - Any prior use of anti-OX40 or anti-OX40L mAb, including amlitelimab - Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study
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E.5 End points |
E.5.1 | Primary end point(s) |
Annualized rate of severe exacerbation events over 48 weeks
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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)Change from baseline in pre-bronchodilator (BD) FEV1 at Week 48 2)Change from baseline in ACQ-5 score at Week 48 3)Change from baseline in Asthma Quality of Life Questionnaire with Standardized Activities (AQLQ (S)) Self-Administered Score at Week 48 4)Change from baseline in post-BD FEV1 at Week 48 5)The absolute change in the percent predicted FEV1 from baseline to Week 48 (pre-BD and post-BD) 6)Change from baseline in ACQ-5 score at Weeks 2, 4, 8, 12, 24, 36, and 60 7)Time to first severe exacerbation event 8)Change from baseline in pre-BD and post-BD FEV1 9)Change from baseline in peak expiratory flow (PEF) and forced expiratory flow (FEF) 25-75% 10)Change from baseline in forced vital capacity (FVC) 11)Change from baseline in FeNO at Weeks 2, 4, 8, 12, 16, 24, 36, 48 and 60 12)Annualized rate of LOAC events during 48 weeks of treatment 13)Time to first LOAC event 14)Change from baseline in the Asthma Daytime Symptom Diary (ADSD) 6-item daily morning score and in the Asthma Nighttime Symptom Diary (ANSD) 7-item daily evening scores at Weeks 2, 4, 8, 12, 24, 36, 48, and 60 15)Annualized rate of severe asthma exacerbations requiring hospitalization or emergency room or urgent care visit during 48 weeks of treatment 16)Change from baseline in the numbers of inhalations/day of SABA or low-dose ICS/formoterol for symptom relief at Weeks 2, 4, 8, 12, 24, 36, 48, and 60 17)Serum amlitelimab concentrations measured throughout the study 18)Incidence of anti-amlitelimab antibody positive response 19)Percentage of participants with treatment-emergent adverse events (TEAEs), including local reactions, AEs of special interest (AESIs), serious adverse events (SAEs) 20)Incidence of potentially clinically significant laboratory test, vital signs, and ECG abnormalities in the treatment period 21)Change from baseline in Asthma Quality of Life Questionnaire with Standardized Activities (AQLQ (S)) Self-Administered Score at Weeks 2, 4, 8, 12, 24, 36, and 60 22)Change from baseline in St. George’s Respiratory Questionnaire (SGRQ) at Weeks 2, 4, 8, 12, 24, 36, 48, and 60 23)Proportion of participants with a decrease from baseline of at least 4 points in SGRQ total score at Week 48 24)Change from baseline in ACQ-6 score and ACQ-7 at Weeks 2, 4, 8, 12, 24, 36, 48, and 60
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1)2)3)4)5)Baseline to Week 48 6)Baseline to Weeks 2, 4, 8, 12, 24, 36, and 60 7)Baseline through Week 48 8)Baseline to Weeks 2, 4, 8, 12,16, 24, 36 and 60 9)Baseline to Weeks 4, 12, 24, 36, 48 and 60 10)Baseline to Weeks 4, 12, 24, 36, 48 and 60 11)Baseline to Weeks 2, 4, 8, 12, 16, 24, 36, 48 and 60 12)Baseline through Week 48 13)Baseline through Week 48 14)Baseline to Weeks 2, 4, 8, 12, 24, 36, 48, and 60 15)Baseline through Week 48 16)Baseline to Weeks 2, 4, 8, 12, 24, 36, 48, and 60 17)Baseline thought Week 60 18)Baseline through Week 60 19)Baseline through Week 60 20)Baseline through Week 60 21)Baseline to Weeks 2, 4, 8, 12, 24, 36, and 60 22)Baseline to Weeks 2, 4, 8, 12, 24, 36, 48, and 60 23)Week 48 24)Baseline to Weeks 2, 4, 8, 12, 24, 36, 48, and 60 |
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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 | No |
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 | 4 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 |
Canada |
Chile |
Japan |
Korea, Republic of |
Mexico |
South Africa |
United States |
Russian Federation |
Turkey |
Hungary |
Italy |
Poland |
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 | |
E.8.9.1 | In the Member State concerned months | 29 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 30 |