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

NCT04631705 | Terminated Phase 1 Results DMC

• 1 other identifier: Uni-Koeln-4370
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 6

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.

Conditions

SARS-CoV-2 Infection

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

  Over first 7 days after study drug administration

Secondary Outcomes (4)

• DZIF-10c Area Under the Curve

  0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose

• Anti-Drug Antibody Development

  0, 14, 28, 56, 90 days post dose

• Time-weighted SARS-CoV-2 Viral Load Change From Baseline

  0, 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

Study Arms (7)

Group 1A (uninfected) - low dose

EXPERIMENTAL

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

Biological: DZIF-10c

Group 1B (uninfected) - mid dose

EXPERIMENTAL

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

Biological: DZIF-10c

Group 1C (uninfected) - high dose

EXPERIMENTAL

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

Biological: DZIF-10c

Group 2A (infected) - low dose

EXPERIMENTAL

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

Biological: DZIF-10c

Group 2B (infected) - mid dose

EXPERIMENTAL

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

Biological: DZIF-10c

Group 2C (infected) - high dose

EXPERIMENTAL

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

Biological: DZIF-10c

Group 2D (infected)

EXPERIMENTAL

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

Biological: DZIF-10c; Drug: Placebo

Interventions

DZIF-10c BIOLOGICAL

Inhaled administration of the human monoclonal antibody DZIF-10c

Group 1A (uninfected) - low dose; Group 1B (uninfected) - mid dose; Group 1C (uninfected) - high dose; Group 2A (infected) - low dose; Group 2B (infected) - mid dose; Group 2C (infected) - high dose; Group 2D (infected)

Placebo DRUG

Inhalation of DZIF-10c diluent as placebo

Group 2D (infected)

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-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)

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 (6)

University Hospital Gießen and Marburg

Giessen, Hesse, 35392, Germany

Location

University Hospital Cologne

Cologne, North Rhine-Westphalia, 50937, Germany

Location

University Hospital Düsseldorf

Düsseldorf, 40225, Germany

Location

University Hospital Frankfurt

Frankfurt am Main, 60590, Germany

Location

University Medical Center Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

LMU Munich University Hospital

Munich, 81377, 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; Respiratory Aspiration

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; Respiration Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

\- Small sample size, further reduced by early termination

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 both healthy volunteers (Groups 1A-1C) and SARS-CoV-2-infected participants (Groups 2A-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).

Study Record Dates

• First Submitted: November 10, 2020
• First Posted: November 17, 2020
• Study Start: December 14, 2020
• Primary Completion: September 23, 2021
• Study Completion: September 23, 2021
• Last Updated: October 3, 2024
• Results First Posted: October 3, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (6)