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

NCT04631666 | Completed Phase 1 Results DMC

• 1 other identifier: Uni-Koeln-4288
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

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.

Conditions

SARS-CoV-2 Infection

Keywords

SARS-CoV-2; Covid-19; Infusion; Monoclonal Antibody

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients With Any AE Within 7 d of Study Drug Infusion

  7 days

Secondary Outcomes (9)

• 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 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

  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

Study Arms (6)

Group 1A (uninfected) - 2.5 mg/kg

EXPERIMENTAL

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

Group 1B (uninfected) - 10 mg/kg

EXPERIMENTAL

SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 10 mg/kg

Biological: DZIF-10c

Group 1C (uninfected) - 40 mg/kg

EXPERIMENTAL

SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 40 mg/kg

Biological: DZIF-10c

Group 1D (uninfected) - high dose

EXPERIMENTAL

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

Group 2C (infected) - 40 mg/kg

EXPERIMENTAL

SARS-CoV-2-infected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 40 mg/kg

Biological: DZIF-10c

Group 2D (infected) - 40 mg/kg

EXPERIMENTAL

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; Other: Placebo

Interventions

DZIF-10c BIOLOGICAL

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

Group 1A (uninfected) - 2.5 mg/kg; Group 1B (uninfected) - 10 mg/kg; Group 1C (uninfected) - 40 mg/kg; Group 1D (uninfected) - high dose; Group 2C (infected) - 40 mg/kg; Group 2D (infected) - 40 mg/kg

Placebo OTHER

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

Group 2D (infected) - 40 mg/kg

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Cologne: lead
• ZKS Köln: collaborator
• Boehringer Ingelheim: collaborator

Study Sites (1)

University Hospital Cologne

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Related Publications (2)

• 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.

  PMID: 32946786 BACKGROUND

• 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.

  PMID: 34473343 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

BI 767551

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Prof. Florian Klein
• Organization: Institute of Virology

florian.klein@uk-koeln.de

49221478

Study Officials

• Gerd Fätkenheuer, MD

  University of Cologne

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigator

Model Details: This study consists of an open-label dose escalation phase in healthy volunteers (Groups 1A-1C) and an additional open-label lead-in phase in SARS-CoV-2-infected individuals (Group 2C). After completion of the dose escalation phase, SARS-CoV-2-infected individuals will be enrolled into a randomized placebo-controlled expansion cohort (Group 2D). An additional higher dose cohort may be included for healthy volunteers (Group 1D).

Study Record Dates

• First Submitted: November 5, 2020
• First Posted: November 17, 2020
• Study Start: December 8, 2020
• Primary Completion: August 11, 2021
• Study Completion: August 11, 2021
• Last Updated: April 8, 2024
• Results First Posted: April 8, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)