Gastroenterology · Clinical trials
Gastro-Oesophageal Reflux Disease (GERD) Clinical Trials
Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.
Indication overview
About gastro-oesophageal reflux disease (gerd) — and why its trials are hard
Gastro-oesophageal reflux disease (GERD) results from retrograde flow of gastric contents into the oesophagus, producing troublesome symptoms such as heartburn and regurgitation and/or mucosal injury. It spans a spectrum from non-erosive reflux disease (NERD) to erosive oesophagitis, and can lead to complications including strictures, Barrett's oesophagus, and, rarely, oesophageal adenocarcinoma. Pathophysiology involves transient lower oesophageal sphincter relaxations, impaired oesophageal clearance, hiatal hernia, and gastric acid. Management combines lifestyle modification with acid suppression. Histamine H2-receptor antagonists provided the first effective pharmacologic acid suppression, but proton pump inhibitors (PPIs) such as omeprazole became the cornerstone of therapy, offering superior healing of erosive oesophagitis and symptom control. A newer class, potassium-competitive acid blockers (P-CABs), typified by vonoprazan, provides faster, more sustained, and pH-independent acid suppression. Vonoprazan gained FDA approval for erosive GERD in 2023 and for non-erosive GERD heartburn in 2024, showing non-inferiority and, in some strata, superiority to PPIs. Despite effective acid suppression, a subset of patients has refractory symptoms, driving interest in reflux-modulating and surgical approaches.
Approved therapies & pivotal evidence
What's been approved — and by how much it moved the endpoint
| Drug (brand) | Approved | Setting | Pivotal trial | Primary endpoint | Magnitude of benefit |
|---|---|---|---|---|---|
| omeprazole (Prilosec) | 1989 | Erosive oesophagitis and GERD symptom relief (first PPI) | Randomized healing trials vs H2RAs | Endoscopic healing of erosive oesophagitis and heartburn relief | Superior erosive-oesophagitis healing rates vs H2-receptor antagonists across trials |
| esomeprazole (Nexium) | 2001 | Erosive oesophagitis healing and maintenance; GERD symptoms | Comparative PPI healing trials | Healing of erosive oesophagitis at 8 weeks | High 8-week healing rates (often >90% in higher-grade disease); modest superiority over some PPIs |
| vonoprazan (Voquezna) | 2023 | Erosive GERD healing/maintenance (potassium-competitive acid blocker); non-erosive GERD heartburn approved 2024 | PHALCON-EE | Non-inferiority in erosive oesophagitis healing over 8 weeks; maintenance of healing | Non-inferior overall healing to lansoprazole, with numerically higher healing in more severe (LA grade C/D) disease |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in gastro-oesophageal reflux disease (gerd) development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| lesogaberan (GABA-B agonist, reflux-reducing add-on) — Phase 2 add-on to PPI | Only modest, clinically marginal reduction in refractory symptoms | Insufficient efficacy over PPI alone to justify further development |
| arbaclofen placarbil (GABA-B agonist prodrug) — Phase 2 GERD program | Failed to demonstrate meaningful benefit on reflux symptom endpoints | Limited efficacy and tolerability concerns led to discontinuation for GERD |
Choosing the right endpoint
Primary endpoints that matter in gastro-oesophageal reflux disease (gerd) trials
- Endoscopic healing of erosive oesophagitis — Mucosal healing by Los Angeles (LA) classification at 4 and 8 weeks; the primary endpoint in erosive GERD trials.
- Percentage of heartburn-free days/24-hour periods — Patient-reported symptom control metric, central to non-erosive GERD trials such as those supporting vonoprazan.
- Maintenance of healing — Proportion remaining healed over 6 months, assessing durability of acid suppression.
- Intragastric pH holding time (pH >4) — Pharmacodynamic measure of acid suppression; P-CABs achieve faster and more sustained pH control than PPIs.
How iNGENū runs gastro-oesophageal reflux disease (gerd) trials
Physician-led design, built for FDA submission
Endpoint & biomarker strategy
Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.
FDA-ready data
Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.
Faster, lower-cost delivery
~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.
Request a fixed-milestone proposal and a tailored endpoint & feasibility summary for this indication.
Frequently asked questions
Gastro-Oesophageal Reflux Disease (GERD) clinical trials — FAQs
How do potassium-competitive acid blockers differ from PPIs?
When was vonoprazan approved for GERD?
Why do some GERD patients not respond to acid suppression?
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