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

NCT ID: NCT04631666

Last Updated: 2024-04-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-08
• Study Completion Date: 2021-08-11

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.

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) - 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

Group Type: EXPERIMENTAL

DZIF-10c

Intervention Type: BIOLOGICAL

SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion

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

Group Type: EXPERIMENTAL

DZIF-10c

Intervention Type: BIOLOGICAL

SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion

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

Group Type: EXPERIMENTAL

DZIF-10c

Intervention Type: BIOLOGICAL

SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion

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

Group Type: EXPERIMENTAL

DZIF-10c

Intervention Type: BIOLOGICAL

SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion

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

Group Type: EXPERIMENTAL

DZIF-10c

Intervention Type: BIOLOGICAL

SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion

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

Group Type: EXPERIMENTAL

DZIF-10c

Intervention Type: BIOLOGICAL

SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion

Placebo

Intervention Type: OTHER

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

Interventions

DZIF-10c

SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion

Intervention Type: BIOLOGICAL

Placebo

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

Intervention Type: OTHER

Eligibility Criteria

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

• 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 Cologne

Cologne, North Rhine-Westphalia, 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-4288

Identifier Type: -

Identifier Source: org_study_id