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

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ClinicalTrials.gov Identifier: NCT04631705
Recruitment Status : Active, not recruiting
First Posted : November 17, 2020
Last Update Posted : August 3, 2021
Sponsor:
Collaborators:
ZKS Köln
Boehringer Ingelheim
Information provided by (Responsible Party):
Florian Klein, University of Cologne

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.

Condition or disease Intervention/treatment Phase
SARS-CoV-2 Infection Biological: DZIF-10c Drug: Placebo Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

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).

Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1/2a Trial of the Inhaled Administration of the SARS-CoV-2-Neutralizing Monoclonal Antibody DZIF-10c in SARS-CoV-2-Infected and -Uninfected Individuals
Actual Study Start Date : December 14, 2020
Estimated Primary Completion Date : September 21, 2021
Estimated Study Completion Date : December 21, 2021

Arm Intervention/treatment
Experimental: Group 1A (uninfected) - low dose
SARS-CoV-2-uninfected volunteers will receive a single dose of DZIF-10c by inhalation
Biological: DZIF-10c
Inhaled administration of the human monoclonal antibody DZIF-10c

Experimental: Group 1B (uninfected) - mid dose
SARS-CoV-2-uninfected volunteers will receive a single dose of DZIF-10c by inhalation
Biological: DZIF-10c
Inhaled administration of the human monoclonal antibody DZIF-10c

Experimental: Group 1C (uninfected) - high dose
SARS-CoV-2-uninfected volunteers will receive a single dose of DZIF-10c by inhalation
Biological: DZIF-10c
Inhaled administration of the human monoclonal antibody DZIF-10c

Experimental: Group 2A (infected) - low dose
SARS-CoV-2-infected volunteers will receive a single dose of DZIF-10c by inhalation
Biological: DZIF-10c
Inhaled administration of the human monoclonal antibody DZIF-10c

Experimental: Group 2B (infected) - mid dose
SARS-CoV-2-infected volunteers will receive a single dose of DZIF-10c by inhalation
Biological: DZIF-10c
Inhaled administration of the human monoclonal antibody DZIF-10c

Experimental: Group 2C (infected) - high dose
SARS-CoV-2-infected volunteers will receive a single dose of DZIF-10c by inhalation
Biological: DZIF-10c
Inhaled administration of the human monoclonal antibody DZIF-10c

Experimental: 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
Biological: DZIF-10c
Inhaled administration of the human monoclonal antibody DZIF-10c

Biological: DZIF-10c
Intravenous administration of the human monoclonal antibody DZIF-10c

Drug: Placebo
Inhalation of DZIF-10c diluent as placebo

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




Primary Outcome Measures :
  1. Rate of Adverse Events after a single DZIF-10c inhalation [Safety and Tolerability] [ Time Frame: 3 months ]
    Primary target variables are (S)AEs and Adverse Events of Special Interest (AESIs)

  2. Rate of Adverse Events after a single combined DZIF-10c inhalation and infusion [Safety and Tolerability] [ Time Frame: 3 months ]
    Primary target variables are (S)AEs and Adverse Events of Special Interest (AESIs)


Secondary Outcome Measures :
  1. Pharmacokinetic parameter AUC0-672 [ Time Frame: 0 to 672 hours ]
    AUC0-672 (the area under the concentration-time curve of DZIF-10c in serum over the time interval from 0 to 672 hours (Day 28)) after inhaled and combined inhaled and intravenous application

  2. Development of anti-drug antibodies [ Time Frame: 3 months ]
    Frequency of the development of anti-drug antibodies targeting DZIF-10c determined by immunoassay

  3. Development of anti-drug antibodies [ Time Frame: 3 months ]
    Titer of anti-drug antibodies targeting DZIF-10c determined by immunoassay

  4. Change in viral load in nasopharyngeal swabs after DZIF-10c administration [ Time Frame: 28 days ]
    Change in SARS-CoV-2 RNA from baseline in nasopharyngeal swabs as determined by qRT-pCR



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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 (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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04631705


Locations
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Germany
University Hospital Gießen and Marburg
Gießen, Hesse, Germany, 35392
University Hospital Cologne
Cologne, NRW, Germany, 50937
University Hospital Düsseldorf
Düsseldorf, Germany, 40225
University Hospital Frankfurt
Frankfurt am Main, Germany, 60590
University Medical Center Hamburg-Eppendorf
Hamburg, Germany, 20246
LMU Munich University Hospital
Munich, Germany, 81377
Sponsors and Collaborators
University of Cologne
ZKS Köln
Boehringer Ingelheim
Investigators
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Principal Investigator: Gerd Fätkenheuer, MD University of Cologne
Publications:
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Responsible Party: Florian Klein, Investigator, University of Cologne
ClinicalTrials.gov Identifier: NCT04631705    
Other Study ID Numbers: Uni-Koeln-4370
First Posted: November 17, 2020    Key Record Dates
Last Update Posted: August 3, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Florian Klein, University of Cologne:
SARS-CoV-2
Covid-19
Monoclonal Antibody
Inhalation