Preclinical Studies of Omalizumab in Chronic Rhinosinusitis With Nasal Polyposis

NCT04583501 | Completed Early Phase 1 FDA Drug

• 1 other identifier: IRB00255799
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this study is to examine the mechanism of action of omalizumab in ex vivo tissue culture of whole human nasal polyps from patients with chronic rhino sinusitis with nasal polyposis (CRSwNP), such that specific molecular markers of inflammation can be identified.

Conditions

Chronic Rhinosinusitis With Nasal Polyps; Nasal Polyps

Keywords

Chronic Rhinosinusitis with Nasal Polyps; eosinophilic nasal polyposis; nasal polyps

Outcome Measures

Primary Outcomes (2)

• IgE tissue compartment distribution in nasal polyps as assessed by quantitative IgE expression

  Quantitative IgE Expression within these cellular compartments will be measured by immunohistochemistry.

  1 year

• Messenger ribonucleic acid (mRNA) expression

  mRNA expression will be analyzed using high throughput RNA sequencing to determine the pattern of inflammatory gene expression.

  1 year

Study Arms (1)

Omalizumab

EXPERIMENTAL

Ex vivo exposure of excised human surgical polyp tissue to omalizumab.

Biological: Omalizumab

Interventions

Omalizumab BIOLOGICAL

Omalizumab will used as dose comparable to to 0.016 mg/kg/IU in serum.

Omalizumab

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sinonasal inflammation for greater than 12 weeks which include at least 2 of the following symptoms: nasal obstruction/congestion, nasal discharge (anterior or posterior), facial pressure/pain, reduction of sense of smell
• Confirmation of the clinical symptoms by (2a) CT scan evidence of paranasal sinus mucosal inflammation, and/or (2b) endoscopic exam evidence of purulence from the sinuses or ostiomeatal complex
• Presence of nasal polyps seen on endoscopic exam or sinus CT scan
• Adults from age of 18-100 will be eligible
• All potential participants will be required to sign an Institutional Review Board (IRB) approved research consent form.

You may not qualify if:

• Children under the age of 18 will be excluded
• The subject groups will also exclude those with disease secondary to a clearly defined anatomic process, such as facial trauma, and obstruction due to sinonasal neoplasm.
• To eliminate confounding variables in our ex vivo experimental studies, any subject with a history of exposure to oral or systemic IV glucocorticoids within 2 weeks of surgery or any immunomodulatory biologics will be excluded. These include, but are not limited to systemic treatment with biologics omalizumab, dupilumab, mepolizumab, benralizumab, reslizumab, or rituximab.

Sponsors & Collaborators

• Johns Hopkins University: lead
• Genentech, Inc.: collaborator

Study Sites (2)

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21117, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Related Publications (5)

• Meltzer EO, Hamilos DL, Hadley JA, Lanza DC, Marple BF, Nicklas RA, Bachert C, Baraniuk J, Baroody FM, Benninger MS, Brook I, Chowdhury BA, Druce HM, Durham S, Ferguson B, Gwaltney JM, Kaliner M, Kennedy DW, Lund V, Naclerio R, Pawankar R, Piccirillo JF, Rohane P, Simon R, Slavin RG, Togias A, Wald ER, Zinreich SJ; American Academy of Allergy, Asthma and Immunology (AAAAI); American Academy of Otolaryngic Allergy (AAOA); American Academy of Otolaryngology--Head and Neck Surgery (AAO-HNS); American College of Allergy, Asthma and Immunology (ACAAI); American Rhinologic Society (ARS). Rhinosinusitis: establishing definitions for clinical research and patient care. J Allergy Clin Immunol. 2004 Dec;114(6 Suppl):155-212. doi: 10.1016/j.jaci.2004.09.029.

  PMID: 15577865 BACKGROUND

• Meltzer EO, Hamilos DL, Hadley JA, Lanza DC, Marple BF, Nicklas RA, Adinoff AD, Bachert C, Borish L, Chinchilli VM, Danzig MR, Ferguson BJ, Fokkens WJ, Jenkins SG, Lund VJ, Mafee MF, Naclerio RM, Pawankar R, Ponikau JU, Schubert MS, Slavin RG, Stewart MG, Togias A, Wald ER, Winther B; Rhinosinusitis Initiative. Rhinosinusitis: Developing guidance for clinical trials. Otolaryngol Head Neck Surg. 2006 Nov;135(5 Suppl):S31-80. doi: 10.1016/j.otohns.2006.09.014.

  PMID: 17081855 BACKGROUND

• Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaert P, Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C, Jones N, Joos G, Kalogjera L, Kern B, Kowalski M, Price D, Riechelmann H, Schlosser R, Senior B, Thomas M, Toskala E, Voegels R, Wang de Y, Wormald PJ. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology. 2012 Mar;50(1):1-12. doi: 10.4193/Rhino12.000.

  PMID: 22469599 BACKGROUND

• Orlandi RR, Kingdom TT, Hwang PH, Smith TL, Alt JA, Baroody FM, Batra PS, Bernal-Sprekelsen M, Bhattacharyya N, Chandra RK, Chiu A, Citardi MJ, Cohen NA, DelGaudio J, Desrosiers M, Dhong HJ, Douglas R, Ferguson B, Fokkens WJ, Georgalas C, Goldberg A, Gosepath J, Hamilos DL, Han JK, Harvey R, Hellings P, Hopkins C, Jankowski R, Javer AR, Kern R, Kountakis S, Kowalski ML, Lane A, Lanza DC, Lebowitz R, Lee HM, Lin SY, Lund V, Luong A, Mann W, Marple BF, McMains KC, Metson R, Naclerio R, Nayak JV, Otori N, Palmer JN, Parikh SR, Passali D, Peters A, Piccirillo J, Poetker DM, Psaltis AJ, Ramadan HH, Ramakrishnan VR, Riechelmann H, Roh HJ, Rudmik L, Sacks R, Schlosser RJ, Senior BA, Sindwani R, Stankiewicz JA, Stewart M, Tan BK, Toskala E, Voegels R, Wang de Y, Weitzel EK, Wise S, Woodworth BA, Wormald PJ, Wright ED, Zhou B, Kennedy DW. International Consensus Statement on Allergy and Rhinology: Rhinosinusitis. Int Forum Allergy Rhinol. 2016 Feb;6 Suppl 1:S22-209. doi: 10.1002/alr.21695.

  PMID: 26889651 BACKGROUND

• Fokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsma S, Toppila-Salmi S, Bernal-Sprekelsen M, Mullol J, Alobid I, Terezinha Anselmo-Lima W, Bachert C, Baroody F, von Buchwald C, Cervin A, Cohen N, Constantinidis J, De Gabory L, Desrosiers M, Diamant Z, Douglas RG, Gevaert PH, Hafner A, Harvey RJ, Joos GF, Kalogjera L, Knill A, Kocks JH, Landis BN, Limpens J, Lebeer S, Lourenco O, Meco C, Matricardi PM, O'Mahony L, Philpott CM, Ryan D, Schlosser R, Senior B, Smith TL, Teeling T, Tomazic PV, Wang DY, Wang D, Zhang L, Agius AM, Ahlstrom-Emanuelsson C, Alabri R, Albu S, Alhabash S, Aleksic A, Aloulah M, Al-Qudah M, Alsaleh S, Baban MA, Baudoin T, Balvers T, Battaglia P, Bedoya JD, Beule A, Bofares KM, Braverman I, Brozek-Madry E, Richard B, Callejas C, Carrie S, Caulley L, Chussi D, de Corso E, Coste A, El Hadi U, Elfarouk A, Eloy PH, Farrokhi S, Felisati G, Ferrari MD, Fishchuk R, Grayson W, Goncalves PM, Grdinic B, Grgic V, Hamizan AW, Heinichen JV, Husain S, Ping TI, Ivaska J, Jakimovska F, Jovancevic L, Kakande E, Kamel R, Karpischenko S, Kariyawasam HH, Kawauchi H, Kjeldsen A, Klimek L, Krzeski A, Kopacheva Barsova G, Kim SW, Lal D, Letort JJ, Lopatin A, Mahdjoubi A, Mesbahi A, Netkovski J, Nyenbue Tshipukane D, Obando-Valverde A, Okano M, Onerci M, Ong YK, Orlandi R, Otori N, Ouennoughy K, Ozkan M, Peric A, Plzak J, Prokopakis E, Prepageran N, Psaltis A, Pugin B, Raftopulos M, Rombaux P, Riechelmann H, Sahtout S, Sarafoleanu CC, Searyoh K, Rhee CS, Shi J, Shkoukani M, Shukuryan AK, Sicak M, Smyth D, Sindvongs K, Soklic Kosak T, Stjarne P, Sutikno B, Steinsvag S, Tantilipikorn P, Thanaviratananich S, Tran T, Urbancic J, Valiulius A, Vasquez de Aparicio C, Vicheva D, Virkkula PM, Vicente G, Voegels R, Wagenmann MM, Wardani RS, Welge-Lussen A, Witterick I, Wright E, Zabolotniy D, Zsolt B, Zwetsloot CP. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020 Feb 20;58(Suppl S29):1-464. doi: 10.4193/Rhin20.600.

  PMID: 32077450 BACKGROUND

MeSH Terms

Conditions

Nasal Polyps

Interventions

Omalizumab

Condition Hierarchy (Ancestors)

Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Polyps; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins

Study Officials

• Jean Kim, MD PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2020
• First Posted: October 12, 2020
• Study Start: December 15, 2020
• Primary Completion: July 12, 2024
• Study Completion: July 12, 2024
• Last Updated: August 13, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)