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

NCT ID: NCT04631705

Last Updated: 2024-10-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-14
• Study Completion Date: 2021-09-23

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.

Conditions

SARS-CoV-2 Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Group 1A (uninfected) - low dose

SARS-CoV-2-uninfected volunteers will receive a single dose of DZIF-10c by inhalation

Group Type: EXPERIMENTAL

DZIF-10c

Intervention Type: BIOLOGICAL

Inhaled administration of the human monoclonal antibody DZIF-10c

Group 1B (uninfected) - mid dose

SARS-CoV-2-uninfected volunteers will receive a single dose of DZIF-10c by inhalation

Group Type: EXPERIMENTAL

DZIF-10c

Intervention Type: BIOLOGICAL

Inhaled administration of the human monoclonal antibody DZIF-10c

Group 1C (uninfected) - high dose

SARS-CoV-2-uninfected volunteers will receive a single dose of DZIF-10c by inhalation

Group Type: EXPERIMENTAL

DZIF-10c

Intervention Type: BIOLOGICAL

Inhaled administration of the human monoclonal antibody DZIF-10c

Group 2A (infected) - low dose

SARS-CoV-2-infected volunteers will receive a single dose of DZIF-10c by inhalation

Group Type: EXPERIMENTAL

DZIF-10c

Intervention Type: BIOLOGICAL

Inhaled administration of the human monoclonal antibody DZIF-10c

Group 2B (infected) - mid dose

SARS-CoV-2-infected volunteers will receive a single dose of DZIF-10c by inhalation

Group Type: EXPERIMENTAL

DZIF-10c

Intervention Type: BIOLOGICAL

Inhaled administration of the human monoclonal antibody DZIF-10c

Group 2C (infected) - high dose

SARS-CoV-2-infected volunteers will receive a single dose of DZIF-10c by inhalation

Group Type: EXPERIMENTAL

DZIF-10c

Intervention Type: BIOLOGICAL

Inhaled administration of the human monoclonal antibody DZIF-10c

Group 2D (infected)

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 Type: EXPERIMENTAL

DZIF-10c

Intervention Type: BIOLOGICAL

Inhaled administration of the human monoclonal antibody DZIF-10c

DZIF-10c

Intervention Type: BIOLOGICAL

Intravenous administration of the human monoclonal antibody DZIF-10c

Placebo

Intervention Type: DRUG

Inhalation of DZIF-10c diluent as placebo

Placebo

Intervention Type: DRUG

Intravenous infusion of sterile normal saline (NaCl 0.9%) as placebo

Interventions

DZIF-10c

Inhaled administration of the human monoclonal antibody DZIF-10c

Intervention Type: BIOLOGICAL

DZIF-10c

Intravenous administration of the human monoclonal antibody DZIF-10c

Intervention Type: BIOLOGICAL

Placebo

Inhalation of DZIF-10c diluent as placebo

Intervention Type: DRUG

Placebo

Intravenous infusion of sterile normal saline (NaCl 0.9%) as placebo

Intervention Type: DRUG

Eligibility Criteria

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

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

ZKS Köln

OTHER

Sponsor Role: collaborator

Boehringer Ingelheim

INDUSTRY

Sponsor Role: collaborator

University of Cologne

OTHER

Sponsor Role: lead

Responsible Party

Florian Klein

Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gerd Fätkenheuer, MD

Role: PRINCIPAL_INVESTIGATOR

University of Cologne

Locations

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

University Medical Center Hamburg-Eppendorf

Hamburg, , Germany

LMU Munich University Hospital

Munich, , Germany

Countries

Germany

References

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.

Reference Type: BACKGROUND

PMID: 32946786 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34473343 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Uni-Koeln-4370

Identifier Type: -

Identifier Source: org_study_id