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

Phase 1

Terminated

• Conditions: SARS-CoV-2 Infection
• Interventions: Biological: DZIF-10c; Drug: Placebo

• Registration Number: NCT04631705
• Lead Sponsor: University of Cologne

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2020-11-10
• Study First Submitted QC: 2020-11-14
• Study First Posted: 2020-11-17
• Study Start: 2020-12-14
• Primary Completion: 2021-09-23
• Study Completion: 2021-09-23
• Results First Submitted: 2022-12-06
• Status Verified: 2024-06
• Results First Submitted QC: 2024-06-19
• Last Update Submitted: 2024-06-19
• Results First Posted: 2024-10-03
• Last Update Posted: 2024-10-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 45

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Group 1A (uninfected) - low dose	DZIF-10c	SARS-CoV-2-uninfected volunteers will receive a single dose of DZIF-10c by inhalation
Group 1B (uninfected) - mid dose	DZIF-10c	SARS-CoV-2-uninfected volunteers will receive a single dose of DZIF-10c by inhalation
Group 2D (infected)	Placebo	SARS-CoV-2-infected volunteers will be randomized 1:1:1 to receive DZIF-10c by inhalation and infusion, DZIF-10c by inhalation and placebo by infusion, or placebo by inhalation and infusion
Group 1C (uninfected) - high dose	DZIF-10c	SARS-CoV-2-uninfected volunteers will receive a single dose of DZIF-10c by inhalation
Group 2A (infected) - low dose	DZIF-10c	SARS-CoV-2-infected volunteers will receive a single dose of DZIF-10c by inhalation
Group 2B (infected) - mid dose	DZIF-10c	SARS-CoV-2-infected volunteers will receive a single dose of DZIF-10c by inhalation
Group 2C (infected) - high dose	DZIF-10c	SARS-CoV-2-infected volunteers will receive a single dose of DZIF-10c by inhalation
Group 2D (infected)	DZIF-10c	SARS-CoV-2-infected volunteers will be randomized 1:1:1 to receive DZIF-10c by inhalation and infusion, DZIF-10c by inhalation and placebo by infusion, or placebo by inhalation and infusion

Primary Outcome Measures

Name	Time	Method
Proportion of Patients With Any AE Within 7 d of Study Drug Administration	Over first 7 days after study drug administration

Secondary Outcome Measures

Name	Time	Method
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; 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.
Anti-Drug Antibody Development	0, 14, 28, 56, 90 days post dose	Individuals developing anti-drug antibodies
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
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

Trial Locations

Locations (6)

University Medical Center Hamburg-Eppendorf; 🇩🇪 Hamburg, Germany

University Hospital Düsseldorf; 🇩🇪 Düsseldorf, Germany

University Hospital Frankfurt; 🇩🇪 Frankfurt am Main, Germany

University Hospital Gießen and Marburg; 🇩🇪 Gießen, Hesse, Germany

University Hospital Cologne; 🇩🇪 Cologne, NRW, Germany

LMU Munich University Hospital; 🇩🇪 Munich, Germany