SARS-CoV-2-Neutralizing Monoclonal COVID-19 Antibody DZIF-10c by Inhalation

This is the first-in-human phase 1/2a trial of the inhaled administration of the SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c in healthy volunteers and SARS-CoV-2-infected individuals. It will evaluate the safety, pharmacokinetic profile, immunogenicity, and antiviral activity of DZIF-10c.

The phase 1 component of this trial consists of a single-inhalation open-label dose-escalation phase (Groups 1A-1C and Groups 2A-2C). Subsequently, the highest tolerated dose tested will be administered to an expansion cohort of SARS-CoV-2-infected individuals (Group 2D). In this randomized and blinded group, participants will receive DZIF-10c or placebo both by inhalation and intravenous infusion.

Eligibility Criteria:
Inclusion Criteria:

Groups 1A-1C

* Age 18-65.
* SARS-CoV-2-RNA negative naso- or oropharyngeal swab obtained within 3 calendar days before study drug administration by NAAT (e.g., qRT-PCR).
* Non-reactivity of serum antibodies (IgG; and IgA and/or IgM when tested) against SARS-CoV-2 by serological assay at screening.

Groups 2A-2D

* Age 18-70.
* SARS-CoV-2-RNA positive naso- or oropharyngeal swab obtained within 3 calendar days before study drug administration by NAAT (e.g., qRT-PCR).
* Onset of COVID-19 symptoms (e.g., sore throat, cough, fever, chills, fatigue, dys- or anosmia, dys- or ageusia, headache, muscle pain, gastrointestinal symptoms) within 7 days prior to study drug administration or Non-reactivity of serum or plasma antibodies (IgG; and IgA and/or IgM when tested) against SARS-CoV-2 by serological assay at screening.
* Disease severity score 1-4 as defined by the WHO Clinical Progression Scale (WHO, Lancet Inf Dis 2020)

Exclusion Criteria (all groups):

* Known hypersensitivity to any constituent of the investigational medicinal product.
* Hepatitis B infection indicated by detectable HBsAg (Hepatitis B surface antigen) in blood.
* Detectable antibodies against hepatitis C virus in blood unless active hepatitis C is ruled out by negative HCV-RNA.
* HIV infection indicated by detectable HIV antigen and/or HIV antibodies in blood.
* Neutrophil count ≤1,000 cells/µl
* Hemoglobin ≤10 g/dl
* Platelet count ≤100,000 cells/µl
* ALT ≥2.0 x ULN
* AST ≥2.0 x ULN
* Total bilirubin ≥1.5 ULN
* eGFR \<60 ml/min/1.73m2
* Pregnancy or lactation.
* Any vaccination within 14 days prior to DZIF-10c administration.
* Receipt of any SARS-CoV-2 vaccine or SARS-CoV-2 monoclonal antibody in the past.
* Diagnosis of bronchial asthma or history of bronchial hyperresponsiveness, COPD, pulmonary fibrosis, or other chronic lung diseases.
* Any chronic or clinically significant medical condition that in the opinion of investigator would jeopardize the safety or rights of the volunteer.
* History of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the trial physician within the last 6 months (a single administration of systemic corticosteroids within ≤6 months and ≥4 weeks of enrollment is acceptable).
* Participation in another clinical trial of an investigational medicinal product within the past 12 weeks or expected participation during this study.
* Dependency on the principal investigator or study staff; or site personnel directly affiliated with this trial.
* Legally incapacitated individuals
* Individuals held in an institution by legal or official order
* If engaging in sexual activity that could result in pregnancy, inability or unwillingness to comply with the requirements for highly effective contraception