Effects of Interleukin (IL)-17A Inhibition on Idiopathic Subglottic Stenosis

Effects of IL-17A Inhibition on Idiopathic Subglottic Stenosis

The purpose of this phase 2 study is to examine if inhibiting IL-17A activation using the biologic drug Taltz, in idiopathic subglottic stenosis patients will decrease scar fibroblast proliferation therefore reducing or eliminating the need for invasive or repeat surgeries.

Study Overview

• Status: Not yet recruiting
• Conditions: Idiopathic Subglottic Stenosis
• Intervention / Treatment: Drug: Taltz

Detailed Description

The purpose of this phase 2 study is to examine if inhibiting IL-17A activation using the biologic drug Taltz, in idiopathic subglottic stenosis patients will decrease scar fibroblast proliferation therefore reducing or eliminating the need for invasive or repeat surgeries. Inhibition of the IL-17A pathway can slow or reverse the inflammation causing airway narrowing in patients with idiopathic subglottic stenosis. This would have a significant impact on quality of life for patients living with this diagnosis as it may help them to avoid frequent surgical procedures, recoveries and associated costs.

This is a single arm, open-label study where all participants will receive drug. The study population is patients with a documented diagnosis of idiopathic subglottic stenosis who are followed at Yale New Haven Hospital.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Nwanmegha Young, MD; Phone Number: (203) 737-1140; Email: Nwanmegha.Young@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale New Haven Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• diagnosis of idiopathic subglottic stenosis

Exclusion Criteria:

• History of active or latent tuberculosis infection
• History of inflammatory bowel disease
• Pregnancy or lactation
• Known allergic reactions to study drug
• Disease involving the vocal cords

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Talz; All participants receive Talz	Drug: Taltz; Participants will receive160 mg (two 80 mg injections) at week 0, followed by 80 mg at weeks 2,4,6,8,10,12 and then 80 mg every 4 weeks; Other Names: Ixekizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in European Quality of Life-Five Dimensions (EQ-5D) Questionnaire	EQ-5D is a standardized measure of health-related quality of life simple, generic questionnaire. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.	Monthly up to 24 months
Change in RAND 36-Item short form health-related quality of life survey	The RAND-36 (SF-36) is the most widely used measure of health-related quality of life survey. It is comprised of 36 items that assess eight health concepts: physical functioning, role limitations caused by physical health problems, role limitations caused by emotional problems, social functioning, emotional well-being, energy/fatigue, pain, and general health perceptions. Scoring the RAND 36-Item Health Survey is a two-step process. First, all items are scored so that a high score defines a more favorable health state. In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved. Second, items in the same scale are averaged together to create the 8 scale scores.	Every 8 weeks from baseline, up to 24 months
Change in Clinical Chronic Obstructive Pulmonary Disease (COPD) Questionnaire (CCQ)	The CCQ consists of three subdomains: symptoms, functional state and mental state. Items are scored on a Likert scale (range 0-60). The final score is the sum of all items divided by 10; separate scores for all three domains can be calculated. Higher scores indicate a worse health status	Monthly up to 24 months
Change in Airway, Dyspnea, Voice, and Swallowing (ADVS) Summary Assessment	A disease-specific Patient-Reported Outcome Measure validated surveys Consists of four domains (airway, dyspnea, voice and swallowing) each scored on 4 point Likert scales of functioning. This summary scale will be used to measure efficacy.	Every 8 weeks from baseline, up to 24 months
Change in Pulmonary function tests (PFT): peak expiratory flow rate in liters/second	Peak expiratory flow rate measures the maximum speed of expiration using a hand held monitor. Patients perform at home PFT weekly and report scores to the study team. Values that are 80 to 100 percent of the normal predicted peak flow readings indicate good lung function.	Weekly up to 96 weeks
Change in PFT: forced expiratory flow rate in liters/second	Forced expiratory flow rate measures the volume of air that can forcibly be blown out in first 1 second, after full inspiration, using a hand held monitor. Patients perform at home PFT weekly and report scores to the study team. Values that are 80 to 120 percent of the normal predicted peak flow readings indicate good lung function.	Weekly up to 96 weeks
Change in PFT: peak inspiratory flow rate in liters/second	Peak inspiratory flow rate measures the maximal flow rate obtained during an inspiratory maneuver using a hand held monitor. Patients perform at home PFT weekly and report scores to the study team. Values that are >60 L/min indicate good lung function.	Weekly up to 96 weeks
Number of weeks between operative interventions	The number of weeks between operative interventions will be counted. Intervention is performed once stenosis related symptoms interfere with daily life. Participants intervals will be compared to their own baseline and national databases (pre-treatment) to assess if IL-17A inhibition prolongs the interval between interventions with prolonged intervals indicating a slower progression to re-stenosis.	From baseline up to 24 months.
Change in degree of stenosis measured by in-office laryngoscopy	Change in degree of stenosis measured by in-office laryngoscopy will be assessed qualitatively every 6 weeks. Degree of stenosis will be assessed as Mild, Moderate or Severe.	Every 6 weeks from baseline up to 24 months

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Lilly PharmaceuticalCompany
• Investigators: Principal Investigator: Nwanmegha Young, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: February 24, 2022
• First Submitted That Met QC Criteria: April 1, 2022
• First Posted (Actual): April 4, 2022

Study Record Updates

• Last Update Posted (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: IL-17a inhibition
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Congenital Abnormalities; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Laryngeal Diseases; Respiratory System Abnormalities; Constriction, Pathologic; Laryngostenosis; Dermatologic Agents; Ixekizumab
• Other Study ID Numbers: 2000031202; No NIH funding (Other Identifier: 10.11.23)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No