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SARS-CoV-2 InfectionPhase 1/2NCT04631705

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

A Phase 1/2 study testing DZIF-10c in people with SARS-CoV-2 Infection, run by University of Cologne at 6 sites in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for
SARS-CoV-2 Infection
What is being tested?
DZIF-10c
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
45 participants
Where
6 sitesGermany
Study dates
14 Dec 2020to 23 Sep 2021
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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)

Who cannot join

  • 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
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  • 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

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Germany6 sites

  • University Hospital Cologne

    Cologne, North Rhine-Westphalia, 50937

  • University Hospital Düsseldorf

    Düsseldorf, 40225

  • University Hospital Frankfurt

    Frankfurt am Main, 60590

  • University Hospital Gießen and Marburg

    Giessen, Hesse, 35392

  • University Medical Center Hamburg-Eppendorf

    Hamburg, 20246

  • LMU Munich University Hospital

    Munich, 81377

Other trials in Germany

About this study

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

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.

Read the 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.

Being tested
DZIF-10c, Placebo
Keywords
SARS-CoV-2, Covid-19, Monoclonal Antibody, Inhalation
Medical subject headings
COVID-19, Respiratory Aspiration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DZIF-10cBiological

    Inhaled administration of the human monoclonal antibody DZIF-10c

  • DZIF-10cBiological

    Intravenous administration of the human monoclonal antibody DZIF-10c

  • PlaceboDrug

    Inhalation of DZIF-10c diluent as placebo

  • PlaceboDrug

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

Study groups in NCT04631705
Study groupRoleWhat they receive
Group 1A (uninfected) - low doseExperimentalSARS-CoV-2-uninfected volunteers will receive a single dose of DZIF-10c by inhalation
Receives: Biological: DZIF-10c
Group 1B (uninfected) - mid doseExperimentalSARS-CoV-2-uninfected volunteers will receive a single dose of DZIF-10c by inhalation
Receives: Biological: DZIF-10c
Group 1C (uninfected) - high doseExperimentalSARS-CoV-2-uninfected volunteers will receive a single dose of DZIF-10c by inhalation
Receives: Biological: DZIF-10c
Group 2A (infected) - low doseExperimentalSARS-CoV-2-infected volunteers will receive a single dose of DZIF-10c by inhalation
Receives: Biological: DZIF-10c
Group 2B (infected) - mid doseExperimentalSARS-CoV-2-infected volunteers will receive a single dose of DZIF-10c by inhalation
Receives: Biological: DZIF-10c
Group 2C (infected) - high doseExperimentalSARS-CoV-2-infected volunteers will receive a single dose of DZIF-10c by inhalation
Receives: Biological: DZIF-10c
Group 2D (infected)ExperimentalSARS-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
Receives: Biological: DZIF-10c; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Over first 7 days after study drug administration

Secondary outcomes (4)

  1. DZIF-10c Area Under the Curve

    Area under the Curve based on serum antibody levels; 4 hour post dose collected in groups 1A-1C and 2A-2C, 1 hour post dose in group 2D (timings referring to last adminstered product); 21 day post dose only in groups 1A-1C. Geometric mean values were only calculated for groups in which at least three individuals with detectable serum levels were included.

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

  2. Anti-Drug Antibody Development

    Individuals developing anti-drug antibodies

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

  3. Time-weighted SARS-CoV-2 Viral Load Change From Baseline

    Time-weighted change of SARS-CoV-2 viral load from baseline in nasopharyngeal swab samples as determined by the SARS-CoV-2 E gene; based on a parametric analysis of covariance model with corresponding baseline viral load, antibody status at baseline, and treatment; determined as the adjusted mean area over the curve (AOC) for samples collected at baseline and 1, 3, 7, 14, 28 days post dose

    Measured: 0, 1, 3, 7, 14, 28 days post dose

  4. MMRM SARS-CoV-2 Viral Load Change From Baseline

    Change of SARS-CoV-2 viral load from baseline in nasopharyngeal swab samples as determined by the SARS-CoV-2 E gene; based on Mixed Model for Repeated Measures (MMRM) with fixed effects for antibody status at BL, LOG10 (viral load) at BL and interaction with visit, treatment-by-visit interaction, and random effect for patient; samples collected at baseline and 1, 3, 7, 14, 28 days post dose

    Measured: 0, 1, 3, 7, 14, 28 days post dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Nov 2020
  2. Study start14 Dec 2020
  3. Primary completion23 Sep 2021
  4. Study completion23 Sep 2021

Why it stopped: Change in viral variant epidemiology

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
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 blind
Who is masked
Participant, Care provider, Investigator
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04631705
Sponsor's protocol ID
Uni-Koeln-4370
Status last verified
Jun 2024
First submitted
10 Nov 2020
Last updated
3 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32946786

  • Kurup S, de Mendizabal NV, Becker S, Bolella E, De Sousa D, Fatkenheuer G, Gruell H, Klein F, Malin JJ, Schmid U, Korell J. Semi-mechanistic population pharmacokinetic modeling of DZIF-10c, a neutralizing antibody against SARS-Cov-2: predicting systemic and lung exposure following inhaled and intravenous administration. J Pharmacokinet Pharmacodyn. 2024 Dec 5;52(1):3. doi: 10.1007/s10928-024-09947-2.

    PubMed 39636474

  • 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.

    PubMed 34473343

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing DZIF-10c in people with SARS-CoV-2 Infection, run by University of Cologne at 6 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 3 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Patients With Any AE Within 7 d of Study Drug Administration (time frame: Over first 7 days after study drug administration). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04631705, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2024.

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