2-Deoxy-D-Glucose in a Human Rhinovirus Challenge Model: a Randomised, Double-blind Placebo-controlled phase 2a clinical trial.

Abstract

Objectives: Rhinovirus causes a significant disease burden in vulnerable individuals, and no vaccine or therapeutic is currently available. A nasal spray containing 2-deoxy-D-glucose (2-DG) was developed as pre-exposure prophylaxis against rhinovirus-associated illness (RAI).

Methods: In this trial, 2-DG was evaluated for its efficacy to prevent RAI in a rhinovirus 39 (RV39) human challenge trial. 2-DG or placebo was self-administered four times per day for seven days in total. Participants completed respiratory symptom questionnaires twice daily in their home environment and paid daily visits to the clinical unit for safety measurements and blood and nasal sampling.

Results: IN TOTAL, 64 PARTICIPANTS WERE RANDOMIZED TO RECEIVE 2-DG OR PLACEBO (1: 1). In the 2-DG group 59.3% of participants developed RAI, compared to 58.6% in the placebo group. Adverse events were mild and comparable between treatment groups. In the 2-DG group, 85.2% developed laboratory-confirmed infection, versus 93.1% in the placebo group. RV39 concentrations and symptom scores did not significantly differ between treatment groups. The study was stopped at a protocol-defined interim analysis because the primary endpoint was not to be achieved.

Conclusion: Intranasal 2-DG showed no efficacy in preventing RAI. The RV39 CHIM proved to be a predictable and reproducible model for early and efficient assessment of efficacy.

Keywords: 2-Deoxy-D-Glucose; CHIM; Clinical trial; Controlled Human Infection Model; Prophylactic Agent; RV39; Respiratory virus; Rhinovirus.