Dupilumab for Aspirin-exacerbated Respiratory Disease

Aspirin-exacerbated Respiratory Disease Clinical Trial

Official title:

Dupilumab as add-on Therapy for Aspirin-exacerbated Respiratory Disease (AERD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03595488
• Other study ID #: 1828-A-18
• Status: Completed
• Phase: Phase 2
• Start date: September 5, 2018
• Est. completion date: December 11, 2019

Study information

• Verified date: August 2020
• Source: Rochester General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Subjects with physician-diagnosed aspirin-exacerbated respiratory disease (AERD) who remain unacceptably symptomatic with a SNOT 22 score > 18 despite routine medical therapy will be enrolled in this single center, single-blinded study assessing the efficacy of dupilumab in AERD.

Description:

This is a single blind, placebo controlled trial to be conducted in adult patients with AERD to determine the efficacy and safety of dupilumab in treating symptoms of chronic rhinosinusitis.

All subjects will be treated with the FDA-approved and the commercially available dose for adult atopic dermatitis of 300 mg every 2 weeks administered subcutaneously, based on the observed efficacy and safety of this dose. In addition to atopic dermatitis, this dose has also been shown to be efficacious in adult asthma.15 Patients will not be treated with a loading dose since other studies of dupilumab in asthma and chronic rhinosinusitis with nasal polyposis have not used a loading dose.

There will be a one month screening period to determine the patient's eligibility and establish symptom control and baseline parameters.

Patients will continue their background medications for chronic rhinosinusitis with nasal polyposis and asthma. These medications may include nasal corticosteroids, nasal antihistamines, systemic antihistamines, leukotriene receptor antagonists, 5 lipo-oxygenase inhibitors, inhaled corticosteroids, long-acting beta agonists, and long acting muscarinic antagonists. These controller medications will not be dispensed or supplied by the sponsor.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: December 11, 2019
• Est. primary completion date: December 11, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients 18 years and older with a physician diagnosis of aspirin-exacerbated respiratory disease, as defined by a physician diagnosis of asthma, chronic rhinosinusitis with nasal polyposis, and a convincing clinical history of NSAID sensitivity

2. All subjects must have a SNOT 22 score = 19 despite standard medical therapy. This minimal SNOT 22 was calculated by taking the range of SNOT 22 scores in studies of normal controls plus 8.9, which is the minimal clinically meaningful improvement in SNOT 22 score detected by patients.

3. Able to understand and willingness to sign informed consent

4. Able to comply with study procedures

Exclusion Criteria:

1. Patient < 18 years of age

2. Pregnancy or breast feeding

3. Current tobacco use

4. Significant, uncontrolled medical conditions

5. Ongoing malignancy or history of malignancy in remission within the past 12 months

6. Current treatment with immunosuppressive medications except chronic oral steroids

7. Currently increasing dose of aeroallergen immunotherapy (patients on stable dose of aeroallergen immunotherapy will be allowed to participate)

8. Treatment with omalizumab, reslizumab, mepolizumab within 4 months of enrollment

Related Conditions & MeSH terms

• Aspirin-exacerbated Respiratory Disease
• Respiration Disorders
• Respiratory Tract Diseases

Intervention

Drug:
• Dupilumab
dupilumab 300 mg subcutaneous injection every 2 weeks

Locations

Country	Name	City	State
United States	Rochester Regional Health - Allergy/Immunology	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
Rochester General Hospital

Country where clinical trial is conducted

United States, 

References & Publications (27)

Bachert C, Mannent L, Naclerio RM, Mullol J, Ferguson BJ, Gevaert P, Hellings P, Jiao L, Wang L, Evans RR, Pirozzi G, Graham NM, Swanson B, Hamilton JD, Radin A, Gandhi NA, Stahl N, Yancopoulos GD, Sutherland ER. Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal Polyposis: A Randomized Clinical Trial. JAMA. 2016 Feb 2;315(5):469-79. doi: 10.1001/jama.2015.19330. — View Citation

Bachert C, Zhang N. Chronic rhinosinusitis and asthma: novel understanding of the role of IgE 'above atopy'. J Intern Med. 2012 Aug;272(2):133-43. doi: 10.1111/j.1365-2796.2012.02559.x. Review. — View Citation

Berges-Gimeno MP, Simon RA, Stevenson DD. Long-term treatment with aspirin desensitization in asthmatic patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2003 Jan;111(1):180-6. — View Citation

Cho KS, Soudry E, Psaltis AJ, Nadeau KC, McGhee SA, Nayak JV, Hwang PH. Long-term sinonasal outcomes of aspirin desensitization in aspirin exacerbated respiratory disease. Otolaryngol Head Neck Surg. 2014 Oct;151(4):575-81. doi: 10.1177/0194599814545750. Epub 2014 Aug 12. — View Citation

Doty RL, Shaman P, Dann M. Development of the University of Pennsylvania Smell Identification Test: a standardized microencapsulated test of olfactory function. Physiol Behav. 1984 Mar;32(3):489-502. — View Citation

Esmaeilzadeh H, Nabavi M, Aryan Z, Arshi S, Bemanian MH, Fallahpour M, Mortazavi N. Aspirin desensitization for patients with aspirin-exacerbated respiratory disease: A randomized double-blind placebo-controlled trial. Clin Immunol. 2015 Oct;160(2):349-57. doi: 10.1016/j.clim.2015.05.012. Epub 2015 Jun 14. — View Citation

Fruth K, Pogorzelski B, Schmidtmann I, Springer J, Fennan N, Fraessdorf N, Boessert A, Schaefer D, Gosepath J, Mann WJ. Low-dose aspirin desensitization in individuals with aspirin-exacerbated respiratory disease. Allergy. 2013;68(5):659-65. doi: 10.1111/all.12131. Epub 2013 Mar 7. — View Citation

Gillett S, Hopkins C, Slack R, Browne JP. A pilot study of the SNOT 22 score in adults with no sinonasal disease. Clin Otolaryngol. 2009 Oct;34(5):467-9. doi: 10.1111/j.1749-4486.2009.01975.x. — View Citation

Hopkins C, Gillett S, Slack R, Lund VJ, Browne JP. Psychometric validity of the 22-item Sinonasal Outcome Test. Clin Otolaryngol. 2009 Oct;34(5):447-54. doi: 10.1111/j.1749-4486.2009.01995.x. — View Citation

Juniper EF, Buist AS, Cox FM, Ferrie PJ, King DR. Validation of a standardized version of the Asthma Quality of Life Questionnaire. Chest. 1999 May;115(5):1265-70. — View Citation

Laidlaw TM, Boyce JA. Aspirin-Exacerbated Respiratory Disease--New Prime Suspects. N Engl J Med. 2016 Feb 4;374(5):484-8. doi: 10.1056/NEJMcibr1514013. — View Citation

Lange B, Thilsing T, Baelum J, Kjeldsen AD. The Sinonasal Outcome Test 22 score in persons without chronic rhinosinusitis. Clin Otolaryngol. 2016 Apr;41(2):127-30. doi: 10.1111/coa.12481. Epub 2016 Feb 4. — View Citation

Lund VJ, Kennedy DW. Staging for rhinosinusitis. Otolaryngol Head Neck Surg. 1997 Sep;117(3 Pt 2):S35-40. Review. — View Citation

Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. — View Citation

Mullol J, Picado C. Rhinosinusitis and nasal polyps in aspirin-exacerbated respiratory disease. Immunol Allergy Clin North Am. 2013 May;33(2):163-76. doi: 10.1016/j.iac.2012.11.002. Epub 2012 Dec 23. Review. Erratum in: Immunol Allergy Clin North Am. 2013 Aug;33(3):xi. — View Citation

Nathan RA, Sorkness CA, Kosinski M, Schatz M, Li JT, Marcus P, Murray JJ, Pendergraft TB. Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol. 2004 Jan;113(1):59-65. — View Citation

Patou J, Gevaert P, Van Zele T, Holtappels G, van Cauwenberge P, Bachert C. Staphylococcus aureus enterotoxin B, protein A, and lipoteichoic acid stimulations in nasal polyps. J Allergy Clin Immunol. 2008 Jan;121(1):110-5. Epub 2007 Nov 5. — View Citation

Rajan JP, Wineinger NE, Stevenson DD, White AA. Prevalence of aspirin-exacerbated respiratory disease among asthmatic patients: A meta-analysis of the literature. J Allergy Clin Immunol. 2015 Mar;135(3):676-81.e1. doi: 10.1016/j.jaci.2014.08.020. Epub 2014 Oct 3. — View Citation

Samuelsson B, Dahlén SE, Lindgren JA, Rouzer CA, Serhan CN. Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science. 1987 Sep 4;237(4819):1171-6. Review. — View Citation

Sommer DD, Hoffbauer S, Au M, Sowerby LJ, Gupta MK, Nayan S. Treatment of aspirin exacerbated respiratory disease with a low salicylate diet: a pilot crossover study. Otolaryngol Head Neck Surg. 2015 Jan;152(1):42-7. doi: 10.1177/0194599814555836. Epub 2014 Oct 24. Erratum in: Otolaryngol Head Neck Surg. 2015 Feb;152(2):378. — View Citation

Sommer DD, Rotenberg BW, Sowerby LJ, Lee JM, Janjua A, Witterick IJ, Monteiro E, Gupta MK, Au M, Nayan S. A novel treatment adjunct for aspirin exacerbated respiratory disease: the low-salicylate diet: a multicenter randomized control crossover trial. Int Forum Allergy Rhinol. 2016 Apr;6(4):385-91. doi: 10.1002/alr.21678. Epub 2016 Jan 11. — View Citation

Stevenson DD, Pleskow WW, Simon RA, Mathison DA, Lumry WR, Schatz M, Zeiger RS. Aspirin-sensitive rhinosinusitis asthma: a double-blind crossover study of treatment with aspirin. J Allergy Clin Immunol. 1984 Apr;73(4):500-7. — View Citation

Swierczynska-Krepa M, Sanak M, Bochenek G, Strek P, Cmiel A, Gielicz A, Plutecka H, Szczeklik A, Nizankowska-Mogilnicka E. Aspirin desensitization in patients with aspirin-induced and aspirin-tolerant asthma: a double-blind study. J Allergy Clin Immunol. 2014 Oct;134(4):883-90. doi: 10.1016/j.jaci.2014.02.041. Epub 2014 Apr 24. — View Citation

Ta V, White AA. Survey-Defined Patient Experiences With Aspirin-Exacerbated Respiratory Disease. J Allergy Clin Immunol Pract. 2015 Sep-Oct;3(5):711-8. doi: 10.1016/j.jaip.2015.03.001. Epub 2015 Apr 7. — View Citation

Waldram JD, White AA. A survey of aspirin desensitization practices among allergists and fellows in training in the United States. J Allergy Clin Immunol Pract. 2016 Nov - Dec;4(6):1253-1255. doi: 10.1016/j.jaip.2016.06.016. Epub 2016 Jul 21. — 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 ß2 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

Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, Wang L, Kirkesseli S, Rocklin R, Bock B, Hamilton J, Ming JE, Radin A, Stahl N, Yancopoulos GD, Graham N, Pirozzi G. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013 Jun 27;368(26):2455-66. doi: 10.1056/NEJMoa1304048. Epub 2013 May 21. — View Citation

* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SNOT 22 Score	This is a patient-reported outcome score for chronic rhinosinusitis with or without nasal polyposis	From baseline to completion of study(7 months total)
Secondary	UPSIT	Univ. of Pennsylvania smell identification test	From baseline to completion of study( 7 months total)
Secondary	Lund Mackay score	Objective score for CT sinus imaging, this is a widely used method for radiologic staging of chronic rhinosinusitis.	From baseline to completion of study( 7 months total)
Secondary	ACT score	Validated asthma control test, a series of 5 questions related to patient's asthma control over the previous 4 weeks.	From baseline to completion of study( 7 months total)
Secondary	Asthma Mini-AQLQ, 15 questions to assess quality of life. This assessment takes approximately 4-5 minutes to complete the questions.	Validated asthma quality of life score	From baseline to completion of study( 7 months total)
Secondary	Change in FEV1	Forced expiratory volume in first second from spirometry	From baseline to completion of study( 7 months total)
Secondary	Change in FeNO	Exhaled nitric oxide	From baseline to completion of study( 7 months total)
Secondary	Eosinophil count	Absolute eosinophil count	From baseline to completion of study( 7 months total)
Secondary	Total serum IgE	Total IgE	From baseline to completion of study( 7 months total)
Secondary	Serum tryptase	Biomarker	From baseline to completion of study( 7 months total)
Secondary	Serum TARC (thymus and activation regulated cytokine)	Biomarker	From baseline to completion of study( 7 months total)
Secondary	Serum prostaglandin D2	Biomarker	From baseline to completion of study( 7 months total)
Secondary	24 hour urinary leukotriene E4	Biomarker	From baseline to completion of study( 7 months total)
Secondary	To assess the safety and tolerability of dupilumab	Adverse events	From baseline to completion of study( 7 months total)
Secondary	To assess cumulative dose of systemic steroids	Impact on systemic steroids	From baseline to completion of study( 7 months total)