# Phase I/IIa Clinical Trial Using Localized and Systemic Delivery of the P2X7 Receptor Antagonist AZD9056 for the Treatment of Salivary Gland Dysfunction in Sjögren's Syndrome Patients

> **NIH NIH R34** · UNIVERSITY OF MISSOURI-COLUMBIA · 2022 · $202,336

## Abstract

Salivary gland dysfunction is a significant medical problem caused by injury or disease, including Sjögren’s
Syndrome (SS), a chronic inflammatory autoimmune disease characterized by hyposalivation and lymphocytic
infiltration of salivary glands (i.e., sialadenitis). Treatments for hyposalivation are limited and deemed to be
inadequate. Thus, development of effective SS treatments is essential. In chronic sialadenitis, alarmins produced
locally in salivary glands promote accumulation of immune cells, tissue degeneration and glandular fibrosis that
exacerbate SS pathogenesis and hyposalivation. Published and preliminary data from the Principal Investigator’s
lab show that localized release of cytoplasmic nucleotide alarmins, such as ATP, from damaged cells activates
the P2X7 receptor (P2X7R) signaling pathway to promote hyposalivation and sialadenitis in SS mouse models,
whereas P2X7R antagonism normalizes saliva production and reduces sialadenitis. Previous work of the Co-
Investigators has established sialendoscopy as a promising therapy for SS-associated hyposalivation, in which
salivary gland ducts are endoscopically irrigated to dilate occlusions. To translate our (pre)clinical findings into an
effective therapeutic intervention, we propose to use contrast-enhanced ultrasound and sialendoscopy (CEUSS)
with gas-filled microbubbles to dissolve ductal occlusions combined with local and systemic application of the
P2X7R antagonist AZD9056 (obtained from Phoenicis), in an anticipated U01 phase I/IIa clinical trial with human
SS patients to reduce sialadenitis and enhance saliva production. This approach will offer unprecedented
possibilities to reduce the burden to patients with SS, while achieving intra-operative diagnostic salivary gland
imaging and evidence of therapeutic efficacy. The anticipated U01 phase I/IIa trial will assess safety, maximum
tolerated dose, pharmacokinetic and pharmacodynamic properties and clinical efficacy of AZD9056 in the first
dose-escalation and cohort-expansion trial with primary SS patients. The trial will determine whether the
combination of intraductal and systemic AZD9056 administration in SS patients inhibits cellular mechanisms
underlying SS using clinical biospecimens.
R34 Specific Aim 1: Develop regulatory plan for intraductal and systemic AZD9056 in SGs of SS patients.
R34 Specific Aim 2: Develop clinical protocol, budget and multinational clinical data management plan for
systemic and intraductal AZD9056 co-administration in SS patients.
R34 Specific Aim 3: Develop protocols for SS patient biospecimens to determine effects of AZD9056 on
mechanisms of SG dysfunction in SS patients.

## Key facts

- **NIH application ID:** 10487866
- **Project number:** 1R34AI155318-01A1
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Arjan Vissink
- **Activity code:** R34 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $202,336
- **Award type:** 1
- **Project period:** 2022-08-08 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10487866

## Citation

> US National Institutes of Health, RePORTER application 10487866, Phase I/IIa Clinical Trial Using Localized and Systemic Delivery of the P2X7 Receptor Antagonist AZD9056 for the Treatment of Salivary Gland Dysfunction in Sjögren's Syndrome Patients (1R34AI155318-01A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10487866. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*