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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
45
University Hospital Gießen and Marburg
Giessen, Hesse, Germany
University Hospital Cologne
Cologne, North Rhine-Westphalia, Germany
University Hospital Düsseldorf
Düsseldorf, Germany
University Hospital Frankfurt
Frankfurt am Main, Germany
Proportion of Patients With Any AE Within 7 d of Study Drug Administration
Time frame: Over first 7 days after study drug administration
DZIF-10c Area Under the Curve
Area under the Curve based on serum antibody levels; 4 hour post dose collected in groups 1A-1C and 2A-2C, 1 hour post dose in group 2D (timings referring to last adminstered product); 21 day post dose only in groups 1A-1C. Geometric mean values were only calculated for groups in which at least three individuals with detectable serum levels were included.
Time frame: 0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose
Anti-Drug Antibody Development
Individuals developing anti-drug antibodies
Time frame: 0, 14, 28, 56, 90 days post dose
Time-weighted SARS-CoV-2 Viral Load Change From Baseline
Time-weighted change of SARS-CoV-2 viral load from baseline in nasopharyngeal swab samples as determined by the SARS-CoV-2 E gene; based on a parametric analysis of covariance model with corresponding baseline viral load, antibody status at baseline, and treatment; determined as the adjusted mean area over the curve (AOC) for samples collected at baseline and 1, 3, 7, 14, 28 days post dose
Time frame: 0, 1, 3, 7, 14, 28 days post dose
MMRM SARS-CoV-2 Viral Load Change From Baseline
Change of SARS-CoV-2 viral load from baseline in nasopharyngeal swab samples as determined by the SARS-CoV-2 E gene; based on Mixed Model for Repeated Measures (MMRM) with fixed effects for antibody status at BL, LOG10 (viral load) at BL and interaction with visit, treatment-by-visit interaction, and random effect for patient; samples collected at baseline and 1, 3, 7, 14, 28 days post dose
Time frame: 0, 1, 3, 7, 14, 28 days post dose
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Intravenous infusion of sterile normal saline (NaCl 0.9%) as placebo
University Medical Center Hamburg-Eppendorf
Hamburg, Germany
LMU Munich University Hospital
Munich, Germany