Preclinical Studies of Omalizumab in Chronic Rhinosinusitis With Nasal Polyposis (CRSwNP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT04583501

Recruitment Status : Recruiting

First Posted : October 12, 2020

Last Update Posted : March 9, 2022

See Contacts and Locations

Sponsor:

Collaborator:

Genentech, Inc.

Information provided by (Responsible Party):

Johns Hopkins University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Chronic Rhinosinusitis With Nasal Polyps Nasal Polyps	Biological: Omalizumab	Early Phase 1

Detailed Description:

Objectives:

Aim 1. The investigation will identify the specific tissue compartment distribution of immunoglobulin E (IgE) expression within human nasal polyps. Colocalization studies will examine functional interaction of IgE with effector cells.

Aim 2. The investigation will examine the direct effect of omalizumab on expression of Type 2, 1, and 3 inflammatory pathways in human nasal polyp tissue from phenotypically characterized chronic rhinosinusitis with nasal polyposis (CRSwNP) patients.

Study Rationale: Human nasal polyps express high local tissue IgE. However, the tissue distribution, cellular location and functional consequence of IgE accumulation within the polyp tissue is not known. Phase 3 studies of omalizumab demonstrated efficacy, with responders. However, the reason for non-responder outcomes in a subset of CRSwNP patients was not understood. Therefore, the goal of this study is to examine the mechanism of action of omalizumab in CRSwNP, such that specific responders for this treatment can be identified and therapy can be optimally directed.

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	8 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Basic Science
Official Title:	Preclinical Studies of Omalizumab in Chronic Rhinosinusitis With Nasal Polyposis
Actual Study Start Date :	December 15, 2020
Estimated Primary Completion Date :	October 2022
Estimated Study Completion Date :	January 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Omalizumab

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Omalizumab Ex vivo exposure of excised human surgical polyp tissue to omalizumab.	Biological: Omalizumab Omalizumab will used as dose comparable to to 0.016 mg/kg/IU in serum.

Outcome Measures

Primary Outcome Measures :

IgE tissue compartment distribution in nasal polyps as assessed by quantitative IgE expression [ Time Frame: 1 year ]
Quantitative IgE Expression within these cellular compartments will be measured by immunohistochemistry.
Messenger ribonucleic acid (mRNA) expression [ Time Frame: 1 year ]
mRNA expression will be analyzed using high throughput RNA sequencing to determine the pattern of inflammatory gene expression.

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	18 Years to 100 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

Children under the age of 18 will be excluded
No pregnant or lactating females, prisoners, mentally disabled, or persons unable to give informed consent will be contemplated for inclusion.
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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04583501

Contacts

Layout table for location contacts

Contact: Jean Kim, MD PhD	410-550-0460	jeankim@jhmi.edu
Contact: Hyun Sil Lee, PhD	410-550-2064	hlee77@jhmi.edu

Locations

Layout table for location information

United States, Maryland
Johns Hopkins Bayview Medical Center	Recruiting
Baltimore, Maryland, United States, 21117
Contact: Jean Kim, MD PhD 410-550-0460 jeankim@jhmi.edu
Contact: Hyun Sil Lee, PhD 410-550-2064 hlee77@jhmi.edu
Johns Hopkins Hospital	Recruiting
Baltimore, Maryland, United States, 21287
Contact: Jean Kim, MD PhD 410-550-0460 jeankim@jhmi.edu
Contact: Hyun Lee, PhD 410-550-2064 hlee77@jhmi.edu

Sponsors and Collaborators

Johns Hopkins University

Genentech, Inc.

Investigators

Layout table for investigator information

Principal Investigator:	Jean Kim, MD PhD	Johns Hopkins University

More Information

Publications:

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. Review.

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.

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.

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. Review.

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.

Layout table for additonal information

Responsible Party:	Johns Hopkins University
ClinicalTrials.gov Identifier:	NCT04583501
Other Study ID Numbers:	IRB00255799
First Posted:	October 12, 2020 Key Record Dates
Last Update Posted:	March 9, 2022
Last Verified:	March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Layout table for additional information

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No
Product Manufactured in and Exported from the U.S.:	No

Keywords provided by Johns Hopkins University:


Chronic Rhinosinusitis with Nasal Polyps eosinophilic nasal polyposis nasal polyps

Additional relevant MeSH terms:

Layout table for MeSH terms

Sinusitis Nasal Polyps Polyps Pathological Conditions, Anatomical Respiratory Tract Infections Infections Paranasal Sinus Diseases	Nose Diseases Respiratory Tract Diseases Otorhinolaryngologic Diseases Omalizumab Anti-Allergic Agents Anti-Asthmatic Agents Respiratory System Agents

To Top