- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04383262
Lexiva for the Treatment of LPR
March 11, 2024 updated by: Nikki Johnston, Medical College of Wisconsin
A 12-Week Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Assess the Efficacy of Fosamprenavir/Lexiva for Laryngopharyngeal Reflux (LPR)
Laryngopharyngeal reflux (LPR) causes chronic cough, throat clearing, hoarseness, and dysphagia and if left untreated can promote the development of laryngeal cancer.
More than 20% of the United Stated population suffer from LPR, yet there is no effective medical therapy.
Proton pump inhibitors (PPIs), which inhibit gastric acid production but do not prevent reflux events, continue to be prescribed for LPR despite their poor efficacy for this patient population, high cost ($26 billion/year), and associated risks.
Pepsin, detected in the airway of these patients and now known to cause laryngeal inflammation and promote disease independent of gastric acid, is a key therapeutic target.
We report preclinical studies of select HIV inhibitors that bind to and inhibit pepsin and thus hold promise for the treatment of LPR.
In support, a very low incidence of LPR was found in patients taking these drugs compared to the general population.
HIV inhibitors are ideal drugs to repurpose because they target a foreign virus.
Thus, a repurposing approach can be used to safely perform proof of concept testing of the efficacy of a pepsin inhibitor for LPR.
The Specific Aim of this project is to perform a 12-week randomized, double-blind, placebo-controlled clinical trial to assess the efficacy of fosamprenavir/Lexiva for LPR.
Lexiva will be used at the FDA approved, manufacturers recommended dose for HIV for 12 weeks in medically refractory patients with clinically diagnosed moderate/severe LPR and combined multi-channel intraluminal impedance - pH (MII-pH) confirmed laryngeal reflux events.
Routine clinical outcome measures for LPR (Reflux Symptom Index and Reflux Finding Score) will be documented pre- and post-treatment with Lexiva (n = 52) and placebo (n = 52).
Saliva will be collected pre- and post-treatment for both pepsin protein analysis and kinetic activity assay to compare with clinical measures.
There is currently no effective medical therapy for LPR and pepsin is the key therapeutic target.
Identification of an FDA approved drug which inhibits pepsin allows for a clinical trial to determine efficacy using a faster and safer repurposing approach to address a significant gap.
Study Overview
Study Type
Interventional
Enrollment (Estimated)
104
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Ally Lesnick, BSc
- Phone Number: (414)955-2659
- Email: alesnick@mcw.edu
Study Contact Backup
- Name: Nikki Johnston, PhD
- Phone Number: (414)736-4437
- Email: njohnston@mcw.edu
Study Locations
-
-
Wisconsin
-
Milwaukee, Wisconsin, United States, 53226
- Ally Lesnick
-
Contact:
- Nikki Johnston, PhD
- Phone Number: (414)736-4437
- Email: njohnston@mcw.edu
-
Contact:
- Ally Lesnick, BSc
- Phone Number: 414-955-2659
- Email: alesnick@mcw.edu
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Clinical diagnosis of LPR
- Age ≥ 18 years
- RSI ≥ 20
- RFS ≥ 11
- Documented LPR by MII-pH testing (>1 proximal event)
- Failed 3 month bid PPI therapy
- Attending laryngology clinic and having flexible laryngoscopy and MII-pH testing per routine clinical care with a minimum of three months between clinic visits (standard practice)
- Patients must be deemed able to comply with the saliva sample collection, treatment plan, and follow-up schedule
- Patients must provide study-specific informed consent prior to study entry
Exclusion Criteria:
- Elderly (age >65 years), pregnant (or plan to be) and nursing mothers as Lexiva not recommended for those populations
- Currently being treated with another investigational medical device and/or drug
- A history of gastric or esophageal surgery
- GI disease that might interfere symptom questionnaire, e.g. IBD
- A history of laryngeal or neck surgery including thyroidectomy and laryngomicroscopic surgery
- Suspected esophageal cancer
- Nasopharyngeal cancer
- Previously undergone anti-reflux surgery
- Polypharmacy (five or more concurrent medications due to comorbidities)
- Potential contradictions or known interactions with Lexiva
- Anticipated poor understanding or compliance of the study protocol
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Lexiva
Lexiva/fosamprenavir at the FDA approved and manufacturers recommended dose (1,400mg twice daily) for 12 weeks
|
A repurposing approach, prospective, placebo-controlled clinical trial of Lexiva (used at the FDA approved, manufacturers recommended dose for HIV (1,400mg twice daily) for 12 weeks in medically refractory patients with clinically diagnosed moderate/severe LPR (RSI ≥ 20, RFS ≥ 11 and MII-pH confirmed laryngeal reflux events).
|
Placebo Comparator: Placebo
standard of care
|
A repurposing approach, prospective, placebo-controlled clinical trial of Lexiva (used at the FDA approved, manufacturers recommended dose for HIV (1,400mg twice daily) for 12 weeks in medically refractory patients with clinically diagnosed moderate/severe LPR (RSI ≥ 20, RFS ≥ 11 and MII-pH confirmed laryngeal reflux events).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Reflux finding score (RFS)
Time Frame: Baseline and 12 weeks of treatment with Lexiva.
|
Clinical scoring system to rate the physical findings of reflux observed upon fiberoptic laryngeal exam.
The scale ranges from 0 (no abnormal findings) to a maximum of 26 (worst score possible).
An RFS greater than 7 indicates that the patient has LPR with 95% certainty.
|
Baseline and 12 weeks of treatment with Lexiva.
|
Change in Reflux Symptom Index (RSI)
Time Frame: Baseline and 12 weeks of treatment with Lexiva.
|
Patient administered questionnaires to assess symptom severity.
The scale ranges from 0 (no abnormal findings) to 45 (worst score possible).
An RSI score greater than 13 is defined as abnormal and indicates LPR.
|
Baseline and 12 weeks of treatment with Lexiva.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in salivary pepsin enzyme activity
Time Frame: Baseline and 12 weeks of treatment with Lexiva.
|
Subjects saliva will be analyzed for pepsin activity by kinetic activity assay.
Salivary pepsin is a biomarker for LPR.
If Lexiva treatment is effective, peptic activity detected prior to treatment (active, yes) will not be detected after treatment (active no).
|
Baseline and 12 weeks of treatment with Lexiva.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Estimated)
June 15, 2024
Primary Completion (Estimated)
October 15, 2025
Study Completion (Estimated)
October 15, 2025
Study Registration Dates
First Submitted
May 1, 2020
First Submitted That Met QC Criteria
May 11, 2020
First Posted (Actual)
May 12, 2020
Study Record Updates
Last Update Posted (Actual)
March 13, 2024
Last Update Submitted That Met QC Criteria
March 11, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Respiratory Tract Diseases
- Gastrointestinal Diseases
- Esophageal Motility Disorders
- Deglutition Disorders
- Esophageal Diseases
- Laryngeal Diseases
- Gastroesophageal Reflux
- Laryngopharyngeal Reflux
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Protease Inhibitors
- HIV Protease Inhibitors
- Viral Protease Inhibitors
- Fosamprenavir
Other Study ID Numbers
- PRO00037954
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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