Objective:

Assess the safety and efficacy of intranasal 2-deoxy-D-glucose (2-DG) versus placebo for preventing rhinovirus-associated illness (RAI) after rhinovirus 39 (RV39) challenge in healthy adults, and establish the challenge model at the study center.

Approach:

• Design and participants: Randomized, double-blind, placebo-controlled phase 2a trial at the Centre for Human Drug Research in Leiden, the Netherlands. Sixty-four healthy adults aged 18–64 years with RV39-specific serum neutralizing antibody titers ≤1:4 were randomized 1:1.
• Intervention and challenge: Intranasal 2-DG, 14 mg per dose, or placebo was administered four times daily, beginning the day before inoculation and continuing through 5 days afterward. Two doses were given on the first and final administration days. Participants received 100 TCID50 of RV39 intranasally.
• Assessments: RAI required symptomatic illness and laboratory-confirmed infection. Assessments included viral testing, antibody responses, Modified Jackson Scores, Wisconsin Upper Respiratory Symptom Survey-21 scores, and safety monitoring.

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, viral loads, and symptom scores did not differ significantly.
• The trial stopped after the planned interim analysis of 64 participants because the recalculated sample size needed to detect a difference was considered infeasible.
• 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.

Interpretation:

The tested regimen showed no measurable preventive benefit against RAI. Safety findings were comparable between groups, and the outpatient RV39 challenge model was successfully implemented.

Limitations:

• Self-administration introduced possible dosing errors or nonadherence.
• Pharmacokinetic data were unavailable to confirm adequate exposure.
• A single rhinovirus type and a challenge dose exceeding natural exposure limit 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.

Sources:

• 2-deoxy-D-glucose in a human rhinovirus challenge model: A randomized, double-blind placebo-controlled phase 2a clinical trial