The goal of this clinical trial is to learn if study drug Fosamprenavir-Sodium Alginate (FOS-SA) administered orally improves symptoms for Proton Pump Inhibitor (PPI)-refractory Gastro Esophageal Reflux Disease (GERD).

The main questions it aims to answer are:

1. Does FOS-SA significantly improve heartburn severity over the 8-week treatment period
2. Does FOS-SA significantly improve regurgitation frequency over the 8-week treatment period
3. Does FOS-SA significantly improve symptoms of persistent GERD over the 8-week treatment period

Researchers will compare FOS-SA to a placebo (a look-alike substance that contains no active drug) to see if FOS-SA works to treat PPI-refractory GERD.

Participants will:

1. Take FOS-SA or placebo every day BID (twice a day) for 8 weeks
2. Visit the Adult Translational Research Unit (ATRU) seven times for consenting, screening, and checkups and tests
3. Keep a daily diary of their symptoms of persistent GERD

Inclusion Criteria:

1. Patient aged 18-65 selected as candidate for anti-reflux surgery by study providers.

2. Patient has received, and continued having GERD symptoms during, standard-labeled dose, daily, PPI therapy for a minimum of 8 weeks before the Screening Visit.

3. Patient has a diagnosis of GERD with endoscopy and/or pH-metry test within the past two years demonstrating 1 or more of the following:

   1. Erosive esophagitis (Grade A or greater based on the Los Angeles classification of esophagitis; Appendix 3)
   2. Evidence of pathological acid reflux (pH < 4 for ≥ 4-6% off therapy or ≥ 1-4% on therapy) during a 24-hour time interval of pH testing

4. Patient reports heartburn severity (HS, Item #1 on mRESQ-eD) ≥ 3 (moderate) on at least 2 days and has an average HS of ≥ 2 (mild) during the last 7 days of the Pretreatment Period before Randomization.

Exclusion Criteria:

1. Patient is suspected of having, functional upper gastrointestinal disorders such as functional dyspepsia or functional heartburn diagnosed by the Rome IV criteria; Appendix 4.
2. Patient has endoscopically confirmed eosinophilic esophagitis (EE).

We have partnered with Froedtert Hospital's Investigative Drug Services (FH IDS) in order to randomize subjects to either treatment or placebo. Only FH IDS will have the key linking subjects to treatment groups, and the power to conduct an emergency un-blinding.