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

A Phase 1/2a Trial of the Intravenous Administration of the SARS-CoV-2-Neutralizing Monoclonal Antibody DZIF-10c in SARS-CoV-2-Infected and -Uninfected Individuals

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.

Study Overview

• Status: Completed
• Conditions: SARS-CoV-2 Infection
• Intervention / Treatment: Biological: DZIF-10c; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • NRW
    • Cologne, NRW, Germany, 50937
      • University Hospital Cologne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1A (uninfected) - 2.5 mg/kg; SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 2.5 mg/kg	Biological: DZIF-10c; SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion
Experimental: Group 1B (uninfected) - 10 mg/kg; SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 10 mg/kg	Biological: DZIF-10c; SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion
Experimental: Group 1C (uninfected) - 40 mg/kg; SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 40 mg/kg	Biological: DZIF-10c; SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion
Experimental: Group 1D (uninfected) - high dose; SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose higher than 40 mg/kg	Biological: DZIF-10c; SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion
Experimental: Group 2C (infected) - 40 mg/kg; SARS-CoV-2-infected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 40 mg/kg	Biological: DZIF-10c; SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion
Experimental: Group 2D (infected) - 40 mg/kg; 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	Biological: DZIF-10c; SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion; Other: Placebo; Intravenous infusion of sterile normal saline (NaCl 0.9%) as placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of Patients With Any AE Within 7 d of Study Drug Infusion	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DZIF-10c Elimination Half Life	DZIF-10c serum elimination half-life	0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose
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 Area Under the Curve	Area under the curve based on serum antibody levels	0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose
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	Individuals developing anti-drug antibodies	0, 14, 28, 56, 90 days post dose
Anti-Drug Antibody Peak Titer	Magnitude of the development of anti-drug antibodies targeting DZIF-10c in individuals developing such antibodies (peak serum titer)	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	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	0, 1, 3, 7, 14, 28 days post dose

Collaborators and Investigators

• Sponsor: University of Cologne
• Collaborators: Boehringer Ingelheim; ZKS Köln
• Investigators: Principal Investigator: Gerd Fätkenheuer, MD, University of Cologne

Publications and helpful links

General Publications

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
• Kreer C, Zehner M, Weber T, Ercanoglu MS, Gieselmann L, Rohde C, Halwe S, Korenkov M, Schommers P, Vanshylla K, Di Cristanziano V, Janicki H, Brinker R, Ashurov A, Krahling V, Kupke A, Cohen-Dvashi H, Koch M, Eckert JM, Lederer S, Pfeifer N, Wolf T, Vehreschild MJGT, Wendtner C, Diskin R, Gruell H, Becker S, Klein F. Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients. Cell. 2020 Sep 17;182(6):1663-1673. doi: 10.1016/j.cell.2020.08.046. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2020
• Primary Completion (Actual): August 11, 2021
• Study Completion (Actual): August 11, 2021

Study Registration Dates

• First Submitted: November 5, 2020
• First Submitted That Met QC Criteria: November 14, 2020
• First Posted (Actual): November 17, 2020

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: October 11, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Covid-19; Monoclonal Antibody; Infusion
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: Uni-Koeln-4288

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No