tetano
Editor, Senior Moderator
Clin Infect Dis
. 2025 Oct 8:ciaf465.
doi: 10.1093/cid/ciaf465. Online ahead of print. Prophylactic Efficacy of CD388, a Novel Drug-Fc Conjugate, in a Human Influenza A/H3N2 Virus Challenge Model: A Randomized, Controlled Phase 2a Study
Roxana E Rojas[SUP] 1 [/SUP], Ozlem Equils[SUP] 2 [/SUP], Jorge Villacian[SUP] 3 [/SUP], Alex Mann[SUP] 4 [/SUP], Wilbert van Duijnhoven[SUP] 3 [/SUP], Johan Vingerhoets[SUP] 3 [/SUP], Tristan Baguet[SUP] 3 [/SUP], Sy-Shi Wang[SUP] 1 [/SUP], Arun Anandakumar[SUP] 4 [/SUP], Antoinette Anger[SUP] 5 [/SUP], Alice Tourneroche[SUP] 5 [/SUP], Isabel Gonçalves Silva[SUP] 4 [/SUP], Shawn Flanagan[SUP] 2 [/SUP]
Affiliations
Background: Influenza is a significant public health concern, especially in immunocompromised patients. CD388 is a novel multivalent zanamivir conjugate that is stably linked to a proprietary human immunoglobulin G1 Fc with a long half-life for prevention of influenza. Here we report a proof-of-concept study on the prophylactic activity of subcutaneously administered CD388 against influenza challenge.
Methods: In a randomized, double-blind, placebo-controlled, phase 2a human challenge study, a single dose of CD388 (50 or 150 mg) was subcutaneously administered in healthy participants 5 days before intranasal challenge with influenza A (H3N2). Safety, pharmacokinetics, infection rate (by reverse transcription-quantitative polymerase chain reaction methods [RT-qPCR]), intranasal viral load (VL), and symptoms were compared between the CD388 and placebo treatment groups.
Results: The area under the VL-time curve (VL-AUC), primary endpoint, was lower in the CD388 150 mg group (n = 28) compared with the placebo group (n = 28; mean 10.70 log10 [copies/mL] × days vs mean 16.09 log10 [copies/mL] × days; P = .0390). Peak VL and the rate of RT-qPCR-confirmed influenza infection were lower in the CD388 group versus the placebo group (P = .0185 and P = .0248, respectively). Clinical symptom scores were numerically lower among participants treated with CD388 compared with participants treated with placebo. There were a limited number of treatment-emergent adverse events. Anti-drug antibody development was rare and not clinically relevant.
Conclusions: CD388 was well-tolerated and demonstrated prophylactic activity against RT-qPCR-confirmed influenza infection in a human challenge study. The efficacy of CD388 in preventing influenza will be confirmed in larger studies. Clinical Trials Registration. ClinicalTrials.gov identifier: NCT05523089.
Keywords: drug–Fc conjugate; human challenge model (HCM) (minimum 1; influenza; maximum 5).
. 2025 Oct 8:ciaf465.
doi: 10.1093/cid/ciaf465. Online ahead of print. Prophylactic Efficacy of CD388, a Novel Drug-Fc Conjugate, in a Human Influenza A/H3N2 Virus Challenge Model: A Randomized, Controlled Phase 2a Study
Roxana E Rojas[SUP] 1 [/SUP], Ozlem Equils[SUP] 2 [/SUP], Jorge Villacian[SUP] 3 [/SUP], Alex Mann[SUP] 4 [/SUP], Wilbert van Duijnhoven[SUP] 3 [/SUP], Johan Vingerhoets[SUP] 3 [/SUP], Tristan Baguet[SUP] 3 [/SUP], Sy-Shi Wang[SUP] 1 [/SUP], Arun Anandakumar[SUP] 4 [/SUP], Antoinette Anger[SUP] 5 [/SUP], Alice Tourneroche[SUP] 5 [/SUP], Isabel Gonçalves Silva[SUP] 4 [/SUP], Shawn Flanagan[SUP] 2 [/SUP]
Affiliations
- PMID: 41060047
- DOI: 10.1093/cid/ciaf465
Background: Influenza is a significant public health concern, especially in immunocompromised patients. CD388 is a novel multivalent zanamivir conjugate that is stably linked to a proprietary human immunoglobulin G1 Fc with a long half-life for prevention of influenza. Here we report a proof-of-concept study on the prophylactic activity of subcutaneously administered CD388 against influenza challenge.
Methods: In a randomized, double-blind, placebo-controlled, phase 2a human challenge study, a single dose of CD388 (50 or 150 mg) was subcutaneously administered in healthy participants 5 days before intranasal challenge with influenza A (H3N2). Safety, pharmacokinetics, infection rate (by reverse transcription-quantitative polymerase chain reaction methods [RT-qPCR]), intranasal viral load (VL), and symptoms were compared between the CD388 and placebo treatment groups.
Results: The area under the VL-time curve (VL-AUC), primary endpoint, was lower in the CD388 150 mg group (n = 28) compared with the placebo group (n = 28; mean 10.70 log10 [copies/mL] × days vs mean 16.09 log10 [copies/mL] × days; P = .0390). Peak VL and the rate of RT-qPCR-confirmed influenza infection were lower in the CD388 group versus the placebo group (P = .0185 and P = .0248, respectively). Clinical symptom scores were numerically lower among participants treated with CD388 compared with participants treated with placebo. There were a limited number of treatment-emergent adverse events. Anti-drug antibody development was rare and not clinically relevant.
Conclusions: CD388 was well-tolerated and demonstrated prophylactic activity against RT-qPCR-confirmed influenza infection in a human challenge study. The efficacy of CD388 in preventing influenza will be confirmed in larger studies. Clinical Trials Registration. ClinicalTrials.gov identifier: NCT05523089.
Keywords: drug–Fc conjugate; human challenge model (HCM) (minimum 1; influenza; maximum 5).