Clinical Report: Phase 2a Trial of 2-Deoxy-D-Glucose in Rhinovirus Challenge

Overview

This phase 2a randomized, double-blind, placebo-controlled trial evaluated intranasal 2-deoxy-D-glucose (2-DG) versus placebo in 64 healthy adults challenged with rhinovirus 39 (RV39). The tested regimen did not demonstrate efficacy in preventing rhinovirus-associated illness (RAI). The trial stopped after a planned interim analysis because the recalculated sample size needed to detect a treatment difference was considered infeasible. Safety findings were comparable between groups.

Background

Rhinoviruses cause upper respiratory infections and can be associated with wheezing, asthma, and more serious illness in vulnerable populations. The article describes rhinovirus management as supportive and symptomatic, with no specific vaccine or therapeutic in clinical use. In preclinical models, 2-DG inhibited glycolysis and reversed infection-associated changes in host-cell metabolism, impairing viral replication. The RV39 controlled human infection model allowed assessment of this investigational approach under controlled conditions.

Objective

Evaluate the safety and efficacy of intranasal 2-DG for preventing RAI after RV39 challenge and establish the reliability and reproducibility of the challenge model at the study center.

Approach

Healthy adults aged 18–64 years with RV39-specific neutralizing antibody titers ≤1:4 were randomized 1:1 to intranasal 2-DG or placebo. Treatment began the day before inoculation and continued through 5 days afterward. The 2-DG dose was 14 mg per administration, four times daily, except on the first and final days, when two doses were administered. All participants received 100 TCID50 of RV39 intranasally.

The primary endpoint was RAI, defined as symptomatic illness with laboratory-confirmed infection. Assessments included viral testing, antibody responses, symptom scores, and safety monitoring.

Data Highlights

Key Findings

• In the primary per-protocol analysis, RAI occurred in 16/27 participants (59.3%) receiving 2-DG and 17/29 (58.6%) receiving placebo.

• Laboratory-confirmed infection occurred in 23/27 participants (85.2%) receiving 2-DG versus 27/29 (93.1%) receiving placebo. Infection rates did not differ significantly.

• Viral loads and Modified Jackson symptom scores did not differ significantly between treatment groups.

• Symptoms were assessed twice daily using the Modified Jackson Score and once daily using the Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21).

• Treatment-emergent adverse events affected 13/32 participants (40.6%) receiving 2-DG and 16/32 (50.0%) receiving placebo. No severe or serious adverse events occurred, and none prompted treatment discontinuation or modification.

• The planned interim analysis after 64 participants indicated that the original target of 128 participants would not be expected to demonstrate a significant difference in RAI. The recalculated sample size was considered infeasible.

• The outpatient RV39 challenge model was successfully implemented at the study center.

Interpretation

The tested intranasal 2-DG regimen showed no measurable benefit in preventing RAI or reducing viral load or symptom severity. The findings illustrate how a controlled human infection model can identify lack of efficacy early in clinical development.

Clinical Implications

The results do not support preventive efficacy for the tested 2-DG regimen. The article describes current rhinovirus care as supportive and symptomatic. Findings should be interpreted within the study’s healthy adult population, dosing schedule, and controlled RV39 exposure.

Limitations

• Self-administration introduced possible dosing errors or nonadherence.

• Pharmacokinetic data were unavailable to confirm adequate exposure.

• RV39 represents one of many rhinovirus types, limiting generalizability.

• The challenge dose exceeded natural exposure, potentially affecting translation to naturally acquired infection.

Conclusion

Intranasal 2-DG did not prevent RAI under the tested conditions. The RV39 challenge model enabled early assessment of the regimen’s lack of efficacy.

Related Resources & Content

1. 2-deoxy-D-glucose in a human rhinovirus challenge model: A randomized, double-blind placebo-controlled phase 2a clinical trial — Victor M. Cnossen, Salma Assil, Marieke L. de Kam, et al. — International Journal of Infectious Diseases. 2026;173:109144. doi:10.1016/j.ijid.2026.109144.

2. Safety, tolerability, and pharmacokinetics of intranasal 2-deoxy-D-glucose in normal healthy volunteers: a randomized, double-blind, placebo-controlled, single and multiple ascending dose phase 1 study — Bischof T, Gsoellpointner M, Miljevic KDK, et al. — European Journal of Pharmaceutical Sciences. 2025;209:107069. doi:10.1016/j.ejps.2025.107069.

3. Rhinovirus induces an anabolic reprogramming in host cell metabolism essential for viral replication — Gualdoni GA, Mayer KA, Kapsch A-M, et al. — Proceedings of the National Academy of Sciences of the United States of America. 2018;115(30):E7158–E7165. doi:10.1073/pnas.1800525115.