E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Rhinosinusitis with Nasal Polyps
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E.1.1.1 | Medical condition in easily understood language |
Chronic Sinusitis with Nasal Polyps |
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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 | 10080060 |
E.1.2 | Term | Chronic rhinosinusitis with nasal polyps |
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 CBP-201 on a background of mometasone furoate nasal spray (MFNS) in reducing endoscopic nasal polyp score (NPS) and nasal congestion/obstruction score (NCS) severity in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) whose disease remains inadequately controlled despite daily treatment with intranasal corticosteroid (INCS) therapy in comparison to placebo.
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of CBP-201 on: • Symptoms of sinusitis • Computed tomography image scores of nasal polyps and sinus inflammation • Patient reported outcomes (PROs) and health-related quality of life (HRQoL) • Safety and tolerability of CBP-201 in patients with CRSwNP
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Female and male patients aged > 18 and < 75 years at the time of screening. 2. Patients who are diagnosed with chronic rhinosinusitis with bilateral polyps despite treatment with systemic corticosteroid within the past 2 years and/or medical contraindication/intolerance to systemic corticosteroids. The polyps have a minimum bilateral NPS of 5 out of a maximum score of 8 with at least a score of 2 for each nostril at screening and baseline evaluated by endoscopy (assessed by independent central readers). 3. Nasal congestion/blockade/obstruction with moderate or severe symptom severity (Nasal Congestion Score of > 2) at screening and a weekly average severity of > 1 at time of randomization. 4. Patients using nasal mometasone at least 200 mcg per day, or equivalent daily dosing of another INCS, for at least 28 days before randomization, and willing to continue for the duration of the study. Note: For patients who are using an alternative INCS product other than MFNS prior to the screening visit, the investigator must switch the patient to MFNS at V1. 5. Patients willing to enter eDiary daily symptom assessments and maintain stable dosing with MFNS with a compliance of at least 70% in the 7 days preceding randomization. Note: Patients must use nasal mometasone at least 200 mcg/day, or equivalent, for at least 28 days before randomization, which can include days prior to screening with supportive documentation. Run-in can be 7-31 days with the compliance determined in the week prior to dosing. 6. Male patients who are nonsterilized and sexually active with a female partner of childbearing potential agree to use highly effective contraception from randomization until 8 weeks after last dose. 7. Female patients of childbearing potential who are sexually active with a nonsterilized male partner should have a confirmed negative serum beta-human chorionic gonadotropin test at Visit 1 and agrees to use highly effective contraception from signing of informed consent throughout the duration of the study and for 8 weeks after last dose. 8. Patient able to read and understand and willing to sign the informed consent form (ICF) prior to any study related procedures being performed. 9. Willing and able to comply with study visits and study-related procedures, in the opinion of the Investigator.
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E.4 | Principal exclusion criteria |
10. Patients unable to use MFNS. 11. Patients who are taking or have taken the following prohibited therapies as specified: a. Systemic steroids within 28 days prior to screening b. Other nonbiologic investigational drugs within 60 days (or 5 half-lives, whichever is longer) of screening c. Intranasal corticosteroid drops or CS-administering devices within 28 days prior to screening d. Non-steroidal immunosuppressants within 60 days or 5 half-lives, whichever is longer, of screening e. Any monoclonal antibody therapy or investigational biologic drug for asthma or other diseases within 60 days or 5 half-lives, whichever is longer, of screening f. Leukotriene antagonists/modifiers within 7 days prior to screening for patients who were not on continuous treatment for ≥ 30 days prior to screening. g. Allergen immunotherapy for patients who were not on maintenance treatment for at least 90 days prior to screening. 12. Patients who did not respond favorably to previous dupilumab treatment. 13. Patients who have undergone any nasal surgery within 6 months before screening; or have a history of sinus or nasal surgery modifying the structure of the nose such that assessment of NPS is not possible, or have had uncontrolled epistaxis requiring surgical or procedural intervention, including nasal packing. 14. Patients with conditions/concomitant diseases making them non evaluable at screening or for the primary efficacy endpoint. 15. Signs or a CT scan suggestive of Allergic Fungal Rhinosinusitis. 16. Patients with co-morbid asthma are excluded if: a. FEV1 ≤ 50% of normal predicted value. OR b. An exacerbation within 90 days prior screening that required hospitalization (> 24 hours). OR c. Are on a daily dose of inhaled corticosteroids (ICS) higher than 1000 mcg fluticasone or the equivalent. 17. Known or suspected history of immunosuppression, including history of invasive opportunistic infections. Tuberculosis testing would be performed on a country by country basis according to local guidelines if required by regulatory authorities or ethics committees. 18. Patients who have active Hepatitis B, Hepatitis C or HIV infections as determined by positive results at Screening for hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb) or hepatitis C (HCV) antibody; or positive HIV serology. 19. A helminth parasitic infection diagnosed within 24 weeks prior to the date of informed consent that has not been treated with, or has failed to respond to, standard of care therapy 20. Evidence of infection requiring treatment with systemic antibacterials, antivirals, antifungals, antiparasitics, or antiprotozoals within 7 days before baseline, or significant viral infections within 14 days before screening that may not have received antiviral treatment. 21. Live, attenuated vaccinations within 28 days prior to screening or planned live, attenuated vaccinations during the study. 22. Pregnant or intent to become pregnant during the study, or breast-feeding women. 23. Any disorder or major physical impairment that is not stable in the opinion of the investigator and may affect the safety of the patient throughout the study, or influence the findings of the studies or their interpretations, or impede the patient’s ability to complete the entire duration of study. 24. Any clinically significant abnormal findings in physical examination, vital signs, safety lab tests during screening/run-in period, which in the opinion of the investigator, may put the patient at risk because of their participation in the study, or may influence the results of the study, or the patient’s ability to complete entire duration of the study 25. Have any of the following laboratory abnormalities at Screening: a. Eosinophils >1500 cells/mm3(or 1.5 x 109/L) b. Platelets <100000 cells/mm3(or 100 x 109/L) c. Creatine phosphokinase (CPK) > 10 upper limit of normal (ULN) d. Alanine aminotransferase (ALT) > 2.5 times the ULN e. Aspartate aminotransferase (AST) ≥ 2.5 times the ULN f. Bilirubin ≥ 2 times the ULN 26. History of alcohol or drug abuse within 12 months prior to the date of informed consent 27. An allergy to L-histidine, trehalose or Tween (polysorbate) 80 or a history of a systemic hypersensitivity reaction, other than localized injection site reaction, to any biologic drug 28. Plans to undergo any surgical procedures requiring general anesthesia during the study. 29. History of cancer: Patients who have had basal cell carcinoma, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that the patient is in remission and curative therapy was completed at least 12 months prior to the date informed consent.
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E.5 End points |
E.5.1 | Primary end point(s) |
There will be 2 co-primary endpoints: • Change from baseline at Week 24 in endoscopic NPS Endoscopic NPS is graded based on polyp size (recorded as the sum of the right and left nostril scores with a range of 0 to 8; higher scores indicate worse status). • Change from baseline at Week 24 in average daily nasal congestion score (NCS)
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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) |
•Change from baseline at Week 24 in: Percentage of maxillary sinus volume occupied by disease on CT and Lund-Mackay Computed Tomography scores University of Pennsylvania Smell Identification Test (UPSIT) Visual analogue scale for rhinosinusitis (VAS-RS) Total nasal symptom score (TNSS) • 22-item Sinonasal Outcome Test (SNOT-22) - Average daily anterior rhinorrhea score (from patient-reported outcomes [PRO] diary) - Average daily posterior rhinorrhea score (from diary) - Average daily loss of smell score (from diary) - Daily subject-assessed nasal peak inspiratory flow (NPIF) • Requirement of rescue treatment (systemic CS for > 5 consecutive days) or having had surgery for nasal polyps through Week 24 • Time to rescue treatment (systemic CS for > 5 consecutive days) or surgery for nasal polyps through Week 24 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | 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 | No |
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 | 9 |
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 |
Belgium |
China |
Poland |
Spain |
Ukraine |
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 | |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 1 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 8 |