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A randomized, double-blind, Phase 1 study of IN-006, an inhaled antibody treatment for COVID-19

Moench et al., medRxiv, doi:10.1101/2022.08.17.22278748, ACTRN12621001235897

Aug 2022

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Regdanvimab

35th treatment shown to reduce risk in March 2022

^*, now with p < 0.00000000001 from 11 studies, recognized in 27 countries. Efficacy is variant dependent.

Lower risk for mortality, hospitalization, progression, and recovery.

No treatment is 100% effective. Protocols combine treatments. ^* >10% efficacy, ≥3 studies.

4,800+ studies for 98 treatments. c19early.org

Phase 1 study of 23 healthy adults showing inhaled regdanvimab (IN-006) was well tolerated after single doses of 30mg and 90mg and 7 daily 90mg doses. High concentrations were achieved in nasal fluids and serum, over 1000 times the inhibitory concentration against SARS-CoV-2 for over 24 hours.

Efficacy is variant dependent. In Vitro research suggests a lack of efficacy for omicron BA.2, BA.4, BA.51, ХВВ.1.9.1, XBB.1.9.3, XBB.1.5.24, XBB.1.16, XBB.2.9, BQ.1.1.45, CL.1, and CH.1.12.

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1. Haars et al., Prevalence of SARS-CoV-2 Omicron Sublineages and Spike Protein Mutations Conferring Resistance against Monoclonal Antibodies in a Swedish Cohort during 2022–2023, Microorganisms, doi:10.3390/microorganisms11102417.mdpi.com, doi.org.

2. Pochtovyi et al., In Vitro Efficacy of Antivirals and Monoclonal Antibodies against SARS-CoV-2 Omicron Lineages XBB.1.9.1, XBB.1.9.3, XBB.1.5, XBB.1.16, XBB.2.4, BQ.1.1.45, CH.1.1, and CL.1, Vaccines, doi:10.3390/vaccines11101533.mdpi.com, doi.org.

Moench et al., 21 Aug 2022, Double Blind Randomized Controlled Trial, placebo-controlled, preprint, 17 authors, trial ACTRN12621001235897. Contact: moench@inhalon.com, lai@inhalon.com.

This Paper Regdanvimab All

A randomized, double-blind, Phase 1 study of IN-006, an inhaled antibody treatment for COVID-19

Thomas R Moench, Lakshmi Botta, Brian Farrer, Jason D Lickliter, Hyunah Kang, Yoona Park, Cheolmin Kim, Marshall Hoke, Miles Brennan, Morgan D Mcsweeney, Zachary Richardson, John B Whelan, Jong Moon Cho, Soo Young Lee, Frances Faurot, Jeff Hutchins, Samuel K Lai

doi:10.1101/2022.08.17.22278748

Rationale: Although COVID-19 is predominantly a respiratory tract infection, current antibody treatments are administered by systemic dosing. We hypothesize that inhaled delivery of a mucotrapping monoclonal antibody would provide a more effective and convenient treatment for COVID-19. Objective: We investigated the safety, tolerability, and pharmacokinetics of IN-006, a reformulation of regdanvimab, an approved intravenous treatment for COVID-19, for nebulized delivery by a handheld nebulizer. Methods: A Phase 1 study was conducted in healthy volunteers. Study staff and participants were blinded to treatment assignment, except for pharmacy staff preparing the study drug. The primary outcomes were safety and tolerability. Exploratory outcomes were pharmacokinetic measurements of IN-006 in nasal fluid and serum. Results: Twenty-three participants were enrolled and randomized across two single dose and one multiple dose cohorts. There were no serious adverse events (SAEs). All enrolled participants completed the study without treatment interruption or discontinuation. All treatment-emergent adverse events were transient, non-dose dependent, and were graded mild to moderate in severity. Nebulization was well tolerated and completed in a mean of 6 minutes in the high dose group. Mean nasal fluid concentrations of IN-006 in the multiple dose cohort were 921 µg/g of nasal fluid at 30 minutes after dosing and 5.8 µg/g at 22 hours. Mean serum levels in the multiple dose cohort peaked at 0.55 µg/mL at 3 days after the final dose. Conclusions IN-006 was well-tolerated and achieved concentrations in the respiratory tract orders of magnitude above its inhibitory concentration. These data support further clinical development of

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We hypothesize that inhaled delivery of a muco-trapping ' 'monoclonal antibody would provide a more effective and convenient treatment for ' 'COVID-19.ObjectiveWe ' 'investigated the safety, tolerability, and pharmacokinetics of IN-006, a reformulation of ' 'regdanvimab, an approved intravenous treatment for COVID-19, for nebulized delivery by a ' 'handheld nebulizer.MethodsA ' 'Phase 1 study was conducted in healthy volunteers. Study staff and participants were blinded ' 'to treatment assignment, except for pharmacy staff preparing the study drug. The primary ' 'outcomes were safety and tolerability. Exploratory outcomes were pharmacokinetic measurements ' 'of IN-006 in nasal fluid and ' 'serum.ResultsTwenty-three ' 'participants were enrolled and randomized across two single dose and one multiple dose ' 'cohorts. There were no serious adverse events (SAEs). All enrolled participants completed the ' 'study without treatment interruption or discontinuation. All treatment-emergent adverse ' 'events were transient, non-dose dependent, and were graded mild to moderate in severity. ' 'Nebulization was well tolerated and completed in a mean of 6 minutes in the high dose group. ' 'Mean nasal fluid concentrations of IN-006 in the multiple dose cohort were 921 µg/g of nasal ' 'fluid at 30 minutes after dosing and 5.8 µg/g at 22 hours. Mean serum levels in the multiple ' 'dose cohort peaked at 0.55 µg/mL at 3 days after the final ' 'dose.ConclusionsIN-006 was ' 'well-tolerated and achieved concentrations in the respiratory tract orders of magnitude above ' 'its inhibitory concentration. 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