Dupilumab Efficacy on Bronchial Inflammation, Small Airways Disfunction and Mucous Secretion

Asthma; Eosinophilic Clinical Trial

— DEBORA  

Official title:

Dupilumab Efficacy on Bronchial Inflammation, Small Airways Disfunction and Mucous Secretion in the Real Life Severe Asthma Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05787678
• Other study ID #: IIBSP-DUP-2022-58
• Status: Recruiting
• Start date: October 1, 2023
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Unicentric prospective real life study designed to analyse the efficacy of Dupilumab to reduce bronchial inflammation of asthma measured by inflammatory cell counts obtained in induced sputum and other related characteristics (small airway dysfunction and mucin production) in uncontrolled severe asthma patients in the real life setting without control group

Description:

After patients signed informed consent, before (visit 1), after 4-5 months (visit 2), and after 12 months (visit 3) Dupilumab treatment began, the following techniques and measurements will be performed or collected: demographic data, blood analyses (eosinophil counts and total IgE), skin prick-test to common aeroallergens (only in the visit 1), asthma control test (ACT), sino-nasal outcome test (SNOT-22), test of adherence to inhalers (TAI), number of severe asthma exacerbations (in the previous year; in the visit 2, in the previous 4 months), oral and inhaled steroid daily doses received, spirometry, exhaled nitric oxide (FeNO), pulmonary volumes, carbon monoxide transference, oscillometry, and induced sputum (inflammatory cell counts and mucin profile [MUC1, MUC2, MUC5AC, MUC5B]). All patients will be performed at visits 1 and 3 in a 3D culture of primary nasal epithelial cells from asthmatic patients the pattern of gene and to identify new soluble biomarkers through quantitative proteomic analysis of culture supernatants.

Also a chest CT scan with expiratory images will be done only in visits 1 and 3.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 18 -80 years

• Severe uncontrolled eosinophilic asthma by GINA (Global Initiative for Asthma) criteria

• Clinical indication of Dupilumab

Exclusion Criteria:

• Smoking over 10 pack/year

• Treatment with monoclonal antibodies treatment during the previous three months

• Refuse to sign informed consent

Related Conditions & MeSH terms

• Asthma
• Asthma; Eosinophilic
• Inflammation
• Pulmonary Eosinophilia

Intervention

Biological:
• Dupilumab
600 mg (two 300 mg injections), followed by 300 mg monthly

Locations

Country	Name	City	State
Spain	Hospital de la Santa Creu i Sant Pau. Carrer Mas Casanovas 90.	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Country where clinical trial is conducted

Spain, 

References & Publications (15)

American Thoracic Society; European Respiratory Society. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med. 2005 Apr 15;171(8):912-30. doi: 10.1164/rccm.200406-710ST. No abstract available. — View Citation

British Thoracic Society; Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma. Thorax. 2014 Nov;69 Suppl 1:1-192. Epub 2014 Oct 16. No abstract available. — View Citation

Castro M, Corren J, Pavord ID, Maspero J, Wenzel S, Rabe KF, Busse WW, Ford L, Sher L, FitzGerald JM, Katelaris C, Tohda Y, Zhang B, Staudinger H, Pirozzi G, Amin N, Ruddy M, Akinlade B, Khan A, Chao J, Martincova R, Graham NMH, Hamilton JD, Swanson BN, Stahl N, Yancopoulos GD, Teper A. Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. N Engl J Med. 2018 Jun 28;378(26):2486-2496. doi: 10.1056/NEJMoa1804092. Epub 2018 May 21. — View Citation

Garcia-Rio F, Calle M, Burgos F, Casan P, Del Campo F, Galdiz JB, Giner J, Gonzalez-Mangado N, Ortega F, Puente Maestu L; Spanish Society of Pulmonology and Thoracic Surgery (SEPAR). Spirometry. Spanish Society of Pulmonology and Thoracic Surgery (SEPAR). Arch Bronconeumol. 2013 Sep;49(9):388-401. doi: 10.1016/j.arbres.2013.04.001. Epub 2013 May 28. English, Spanish. — View Citation

Magnussen H, Holz O, Sterk PJ, Hargreave FE. Noninvasive methods to measure airway inflammation: future considerations. Eur Respir J. 2000 Dec;16(6):1175-9. doi: 10.1034/j.1399-3003.2000.16f25.x. — View Citation

Paggiaro PL, Chanez P, Holz O, Ind PW, Djukanovic R, Maestrelli P, Sterk PJ. Sputum induction. Eur Respir J Suppl. 2002 Sep;37:3s-8s. doi: 10.1183/09031936.02.00000302. No abstract available. — View Citation

Pepys J. Skin tests. Br J Hosp Med. 1984 Sep;32(3):120, 122, 124. — View Citation

Pizzichini E, Pizzichini MM, Efthimiadis A, Evans S, Morris MM, Squillace D, Gleich GJ, Dolovich J, Hargreave FE. Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):308-17. doi: 10.1164/ajrccm.154.2.8756799. — View Citation

Plaza V, Alobid I, Alvarez C, Blanco M, Ferreira J, Garcia G, Gomez-Outes A, Gomez F, Hidalgo A, Korta J, Molina J, Pellegrini FJ, Perez M, Plaza J, Praena M, Quirce S, Sanz J. Spanish Asthma Management Guidelines (GEMA) VERSION 5.1. Highlights and Controversies. Arch Bronconeumol. 2022 Feb;58(2):150-158. doi: 10.1016/j.arbres.2021.05.010. Epub 2021 May 26. English, Spanish. — View Citation

Rabe KF, Nair P, Brusselle G, Maspero JF, Castro M, Sher L, Zhu H, Hamilton JD, Swanson BN, Khan A, Chao J, Staudinger H, Pirozzi G, Antoni C, Amin N, Ruddy M, Akinlade B, Graham NMH, Stahl N, Yancopoulos GD, Teper A. Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma. N Engl J Med. 2018 Jun 28;378(26):2475-2485. doi: 10.1056/NEJMoa1804093. Epub 2018 May 21. — View Citation

Sanjuas C, Alonso J, Sanchis J, Casan P, Broquetas JM, Ferrie PJ, Juniper EF, Anto JM. [The quality-of-life questionnaire with asthma patients: the Spanish version of the Asthma Quality of Life Questionnaire]. Arch Bronconeumol. 1995 May;31(5):219-26. doi: 10.1016/s0300-2896(15)30927-3. Spanish. — View Citation

Vega JM, Badia X, Badiola C, Lopez-Vina A, Olaguibel JM, Picado C, Sastre J, Dal-Re R; Covalair Investigator Group. Validation of the Spanish version of the Asthma Control Test (ACT). J Asthma. 2007 Dec;44(10):867-72. doi: 10.1080/02770900701752615. — View Citation

Vidal S, Bellido-Casado J, Granel C, Crespo A, Plaza V, Juarez C. Flow cytometry analysis of leukocytes in induced sputum from asthmatic patients. Immunobiology. 2012 Jul;217(7):692-7. doi: 10.1016/j.imbio.2011.11.008. Epub 2011 Dec 2. — View Citation

Wechsler ME, Ford LB, Maspero JF, Pavord ID, Papi A, Bourdin A, Watz H, Castro M, Nenasheva NM, Tohda Y, Langton D, Cardona G, Domingo C, Park HS, Chapman KR, Mao X, Zhang Y, Khan AH, Deniz Y, Rowe PJ, Kapoor U, Khokhar FA, Mannent LP, Ruddy M, Laws E, Amin N, Hardin M. Long-term safety and efficacy of dupilumab in patients with moderate-to-severe asthma (TRAVERSE): an open-label extension study. Lancet Respir Med. 2022 Jan;10(1):11-25. doi: 10.1016/S2213-2600(21)00322-2. Epub 2021 Sep 28. — View Citation

Wenzel S, Castro M, Corren J, Maspero J, Wang L, Zhang B, Pirozzi G, Sutherland ER, Evans RR, Joish VN, Eckert L, Graham NM, Stahl N, Yancopoulos GD, Louis-Tisserand M, Teper A. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting beta2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016 Jul 2;388(10039):31-44. doi: 10.1016/S0140-6736(16)30307-5. Epub 2016 Apr 27. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of bronchial inflammatory cells	Count of induced sputum leucocytes	1 year
Secondary	Mucin production from epithelial cells	Levels of MUC 1, MUC2, MUC5AC, and MUC5B	1 year