Ivacaftor for Acquired CFTR Dysfunction in Chronic Rhinosinusitis

NCT03439865 | Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: IRB-3000001685R01HL133006-02
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this pilot study is to explore wither ivacaftor in refractory CRS patients will demonstrate safety and tolerability; restore CFTR-mediated Cl- secretions as measured by EDSPD testing; produce detectable improvements in validated measures of CRS including the SNOT-22 questionnaire, Lund-MacKay CT scan grading, and Lund-Kennedy endoscopic scores; and provide beneficial effects on readily measured markers of sinonasal inflammation and infection (IP-10, IL-8, and Pseudomonas CFUs).

Conditions

Chronic Rhinosinusitis (Diagnosis)

Outcome Measures

Primary Outcomes (1)

• Improvement in quality of life measures

  Comparison of 22-tem Sino-Nasal Outcomes Test (SNOT-22) scores collected at Screening, Day 1, Day 14, and Day 30. The SNOT-22 is a 22-item questionnaire about rhinosinusitis symptoms and the social/emotional consequences for quality of life. The Likert scale ranges from 1-5, where 1 = "No Problem" and 5 = "Problem as bad as it can be." A total score is collected, ranging from 0-110; the higher the score, the worse the outcome.

  Screening to Day 30

Study Arms (2)

standard of care treatment + ivacaftor

EXPERIMENTAL

topical nasal steroid spray and culture-directed antibiotics + ivacaftor 150 mg tablet

Drug: Ivacaftor; Drug: standard of care treatment

standard of care treatment

PLACEBO COMPARATOR

topical nasal steroid spray and culture-directed antibiotics

Drug: standard of care treatment

Interventions

Ivacaftor DRUG

150 mg tablet PO BID x 14 days

Also known as: Kalydeco

standard of care treatment + ivacaftor

standard of care treatment DRUG

topical nasal steroid spray and culture-directed antibiotics x 14 days

standard of care treatment; standard of care treatment + ivacaftor

Eligibility Criteria

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

You may qualify if:

• years of age
• Patient has provided informed consent
• Diagnosis of CRS made by one of the investigators
• Standard of care CT scan with definitive demonstration of isolated or diffuse mucosal thickening, bone changes, and air fluid levels, obtained within 30 days of treatment
• Positive culture of at least one gram negative bacteria (e.g. Pseudomonas, E. coli, Steenotrophomonas) within 30 days prior to testing
• Previous surgery with (at least) exposed maxillary and ethmoid sinuses
• Ability to perform EDSPD testing such that nasal cavity space and sinus openings are sufficient for catheter placement
• Negative pregnancy test for females of childbearing potential within 72 hours of testing and start of study treatment

You may not qualify if:

• \< 18 years of age
• Acute illness other than sinusitis within 2 weeks before start of study treatment that, in the opinion of the investigator, would preclude participation
• Currently taking medications that are moderate or strong CP3A inhibitors
• History of asthma attack requiring emergency room visit or treatment with oral steroids within 2 months prior to study treatment
• History of solid organ or hematological transplantation
• History of known immunodeficiency, autoimmune or granulomatous disorder
• Serum creatinine \> 1.5x upper normal limit
• Abnormal liver function, as defined by serum AST \> 2x upper normal limit, serum ALT \> 2x upper normal limit, Alkaline phosphatase \> 2x upper normal limit, Total bilirubin \> 2x upper normal limit
• Women who are pregnant or breastfeeding

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

RECRUITING

Related Publications (1)

• Karanth TK, Karanth VKLK, Ward BK, Woodworth BA, Karanth L. Medical interventions for chronic rhinosinusitis in cystic fibrosis. Cochrane Database Syst Rev. 2022 Apr 7;4(4):CD012979. doi: 10.1002/14651858.CD012979.pub3.

  PMID: 35390177 DERIVED

MeSH Terms

Conditions

Disease

Interventions

ivacaftor

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Bradford Woodworth, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Norma Miller, RN

CONTACT

(205) 975-6169; ncmiller@uabmc.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 14, 2018
• First Posted: February 20, 2018
• Study Start: May 2, 2019
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)