E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic rhinosinusitis without nasal polyposis |
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E.1.1.1 | Medical condition in easily understood language |
Chronic rhinosinusitis without nasal polyposis |
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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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009137 |
E.1.2 | Term | Chronic sinusitis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 dupilumab as assessed by the reduction at Week 24 in sinus opacification on computerized tomography (CT) scan in the dupilumab group only
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E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy of dupilumab as assessed by the reduction at Week 24 in sinus opacification on CT scan and sinus total symptom score (sTSS) compared to placebo - To evaluate the safety and tolerability of dupilumab in CRSsNP patients compared to placebo - To evaluate the pharmacokinetics (PK) of dupilumab in CRSsNP patients compared to placebo - Assessment of immunogenicity to dupilumab over time compared to placebo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Participant must be at least 18 years of age at the time of signing the informed consent form (ICF). - Participants must have bilateral inflammation of paranasal sinuses in CT scan with LMK ≥8 and bilateral ethmoid opacification before randomization. - Participants must have ongoing symptoms of loss of smell and rhinorrhea (anterior/posterior) of any severity, with or without facial pain/pressure for at least 12 consecutive weeks by Visit 1. - Participants must have ongoing symptoms of nasal congestion (NC)/obstruction at least 12 consecutive weeks before Visit 1 and a NC score of ≥ 2 at Visit 1 (day score) and Visit 2 (weekly average score). - Participants must have sTSS (NC, rhinorrhea, facial pain/pressure) ≥5 at Visit 1 (day score) and Visit 2 (weekly average score). - Participants must have one of the 2 following features: o Prior sinonasal surgery (see note at end of section 5.2 for definitions of sinonasal surgery) for CRS, o Treatment with SCS therapy for CRS as defined by any dose and duration within the prior 2 years before screening (Visit 1) or intolerance/contraindication to SCS. |
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E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria apply: - Patients with nasal conditions/concomitant nasal diseases such as nasal polyposis in endoscopy at Visit 1 or with history of nasal polyposis etc., making them non-evaluable at Visit 1 or for the primary efficacy - Nasal cavity malignant tumor and benign tumors. - Forced expiratory volume (FEV1) ≤50% of predicted normal at Visit 1. - Radiologic suspicion or confirmed invasive or expansive fungal rhinosinusitis. - Severe concomitant illness(es) that, in the investigator’s judgment, would adversely affect the patient’s participation in the study - Active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis unless documented adequately treated. - Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection - Known or suspected immunodeficiency - History of malignancy within 5 years before Visit 1, except completely treated in situ carcinoma of the cervix, and completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin. - Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the Screening Visit 1 or during the screening period. - History of systemic hypersensitivity or anaphylaxis to dupilumab or any of its excipients. - Patients in prior dupilumab clinical trial or have been treated with commercially available dupilumab within 12 months or who discontinued dupilumab use due to adverse event. - Patients who are treated with intranasal corticosteroid drops; intranasal steroid emitting devices/stents; nasal spray using exhalation delivery system, such as Xhance™, during screening period. - Participants on unstable dose of INCS spray 4 weeks prior to Screening Visit (Visit1) and during screening period. - Patients who have undergone sinus intranasal surgery (including polypectomy) within 6 months prior to Visit 1. - Patients who have taken: o Biologic therapy/systemic immunosuppressant to treat inflammatory disease or autoimmune disease within 5 half-lives prior to Visit 1 o Any investigational mAb within 5 half-lives prior to Visit 1 o Anti-IgE therapy (omalizumab) within 4 months prior to Visit 1. -Treatment with a live (attenuated) vaccine within 4 weeks prior to Visit 1 - Leukotriene antagonists/modifiers unless patient is on a continuous treatment for at least 30 days prior to Visit 1. - Initiation of allergen immunotherapy within 3 months prior to Visit 1 or a plan to begin therapy or change its dose during the screening or treatment period. - Patients received SCS during screening period(between Visit 1 and Visit 2). - Either intravenous immunoglobulin therapy and/or plasmapheresis within 30 days prior to Screening Visit (Visit 1). |
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E.5 End points |
E.5.1 | Primary end point(s) |
1 - Change from baseline to Week 24 in opacification of sinuses assessed by CT scan using the Lund Mackay (LMK) score in the dupilumab group only; LMK total score is based on assessment of the CT scan findings for each sinus area. The extent of opacification is rated between 0 (normal) to 24 (total opacification). |
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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 to Week 24 in opacification of sinuses assessed by CT scan using the LMK score 2 - Change from baseline to Week 24 in sTSS 3 -Incidence of treatment-emergent adverse events (TEAEs), of treatment-emergent serious AEs (TESAEs), and TEAEs leading to treatment discontinuation 4 - Dupilumab concentration in serum 5 - Incidence of treatment-emergent anti-drug antibodies (ADA) to dupilumab over time
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 2 : Baseline to Week 24 4 : Baseline to Week 52 3,5 : Baseline to Week 64 |
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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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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 | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
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 |
Australia |
Canada |
Chile |
China |
India |
Japan |
Korea, Republic of |
Mexico |
United States |
Russian Federation |
Ukraine |
Austria |
Belgium |
Germany |
Hungary |
Italy |
Poland |
Portugal |
Romania |
Spain |
Sweden |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 10 |