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

Phase 1

Completed

Conditions: SARS-CoV-2 Infection

Interventions: Biological: DZIF-10c
Other: Placebo

Registration Number: NCT04631666

Lead Sponsor: University of Cologne

Brief Summary: This is the first-in-human phase 1/2a trial of the intravenous 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.

Detailed Description: The phase 1 component of this trial consists of a single intravenous infusion open-label dose-escalation phase (Groups 1A-1D and Group 2C). Subsequently, the highest tested and tolerated dose 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 by intravenous infusion.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 57

Inclusion Criteria

Groups 1A-1D

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 2C-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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Group 2C (infected) - 40 mg/kg	DZIF-10c	SARS-CoV-2-infected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 40 mg/kg
Group 1B (uninfected) - 10 mg/kg	DZIF-10c	SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 10 mg/kg
Group 1D (uninfected) - high dose	DZIF-10c	SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose higher than 40 mg/kg
Group 1C (uninfected) - 40 mg/kg	DZIF-10c	SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 40 mg/kg
Group 2D (infected) - 40 mg/kg	DZIF-10c	SARS-CoV-2-infected volunteers will be randomized 2:1 to receive an intravenous infusion of DZIF-10c at a dose of 40 mg/kg or placebo
Group 1A (uninfected) - 2.5 mg/kg	DZIF-10c	SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 2.5 mg/kg
Group 2D (infected) - 40 mg/kg	Placebo	SARS-CoV-2-infected volunteers will be randomized 2:1 to receive an intravenous infusion of DZIF-10c at a dose of 40 mg/kg or placebo

Primary Outcome Measures

Name	Time	Method
Proportion of Patients With Any AE Within 7 d of Study Drug Infusion	7 days

Secondary Outcome Measures

Name	Time	Method
DZIF-10c Peak Serum Concentration	0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose
DZIF-10c Elimination Half Life	0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose	DZIF-10c serum elimination half-life
DZIF-10c Area Under the Curve	0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose	Area under the curve based on serum antibody levels
DZIF-10c Clearance	0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose
DZIF-10c Volume of Distribution Vz	0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose
Anti-Drug Antibody Development	0, 14, 28, 56, 90 days post dose	Individuals developing anti-drug antibodies
Anti-Drug Antibody Peak Titer	0, 14, 28, 56, 90 days post dose	Magnitude of the development of anti-drug antibodies targeting DZIF-10c in individuals developing such antibodies (peak serum titer)
MMRM SARS-CoV-2 Viral Load Change From Baseline	0, 1, 3, 7, 14, 28 days post dose	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-weighted SARS-CoV-2 Viral Load Change From Baseline	0, 1, 3, 7, 14, 28 days post dose	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