Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025
Prophylactic Efficacy of CD388, a Novel Drug-Fc Conjugate, in a Human Influenza A/H3N2 Virus Challenge Model: A Randomized, Controlled Phase 2a Study.
СтатьяРандомизированное исследованиеКлиническое исследование II фазыПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Rojas Roxana E, Equils Ozlem, Villacian Jorge, Mann Alex, van Duijnhoven Wilbert, Vingerhoets Johan, Baguet Tristan, Wang Sy-Shi, Anandakumar Arun, Anger Antoinette, Tourneroche Alice, Silva Isabel Gonçalves, Flanagan Shawn
Аннотация
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.
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.