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.
Biological: DZIF-10c
Inhaled administration of the human monoclonal antibody DZIF-10c
Biological: DZIF-10c
Intravenous administration of the human monoclonal antibody DZIF-10c
Drug: Placebo
Inhalation of DZIF-10c diluent as placebo
Drug: Placebo
Intravenous infusion of sterile normal saline (NaCl 0.9%) as placebo
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
University Hospital Gießen and Marburg
Gießen, Hesse, Germany
University Hospital Cologne
Cologne, NRW, Germany
University Hospital Düsseldorf
Düsseldorf, Germany
University Hospital Frankfurt
Frankfurt am Main, Germany
University Medical Center Hamburg-Eppendorf
Hamburg, Germany
LMU Munich University Hospital
Munich, Germany
Gerd Fätkenheuer, MD, Principal Investigator
University of Cologne