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TerminatedNCT04631705Updated Oct 3, 2024Results posted

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

A Phase 1/2 interventional study of DZIF-10c and DZIF-10c in SARS-CoV-2 Infection, sponsored by University of Cologne. Terminated at 6 sites in Germany. Open to participants aged 18 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-10-03.

Sponsored by University of Cologne · Phase 1/2, Interventional, and Treatment

Why this study was terminated
Change in viral variant epidemiology
Phase
Phase 1/2
Study type
Interventional
Enrollment
45
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study 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 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.

02

Conditions studied

  • SARS-CoV-2 Infection

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Keywords

  • SARS-CoV-2
  • Covid-19
  • Monoclonal Antibody
  • Inhalation
03

In context

COVID-19

7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.

This study's enrollment of 45 is below the median of 100 across 4,099 interventional studies indexed under COVID-19.

Browse COVID-19 studies →

Lead sponsor

University of Cologne is the lead sponsor of 199 studies on the registry; 26 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Sequential assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
45 participants (actual)

Study arms

  • Experimental
    Group 1A (uninfected) - low dose

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

    Biological: 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

  • Experimental
    Group 1C (uninfected) - high dose

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

    Biological: 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

  • Experimental
    Group 2B (infected) - mid dose

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

    Biological: 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

  • 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 · Drug: Placebo

Interventions

  • BiologicalDZIF-10c

    Inhaled administration of the human monoclonal antibody DZIF-10c

  • BiologicalDZIF-10c

    Intravenous administration of the human monoclonal antibody DZIF-10c

  • DrugPlacebo

    Inhalation of DZIF-10c diluent as placebo

  • DrugPlacebo

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

06

What researchers measure

Primary outcomes

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

    Time frame: Over first 7 days after study drug administration

Secondary outcomes

  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.

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 0, 1, 3, 7, 14, 28 days post dose

07

Results

Posted Oct 3, 2024
Limitations and caveats
- Small sample size, further reduced by early termination

Participant flow

Participant flow — Overall Study
Milestone1A: Healthy, 50 mg Inh.1B: Healthy, 100 mg Inh.1C: Healthy, 250 mg Inh.2A: Infected, 50 mg Inh.2B: Infected, 100 mg Inh.2C: Infected, 250 mg Inh.2D: Infected, Placebo Inh., Placebo i.v.2D: Infected, 250 mg Inh., Placebo i.v.2D: Infected, 250 mg Inh., 40 mg/kg i.v.
Started3333331089
Completed333333989
Not completed000000100
Withdrew: Withdrawal by subject000000100

Outcome measures

PrimaryProportion of Patients With Any AE Within 7 d of Study Drug Administration
Time frame:
Over first 7 days after study drug administration
Reported as:
Count of participants · Participants
Proportion of Patients With Any AE Within 7 d of Study Drug Administration
Participants1A: Healthy, 50 mg Inh.1B: Healthy, 100 mg Inh.1C: Healthy, 250 mg Inh.2A: Infected, 50 mg Inh.2B: Infected, 100 mg Inh.2C: Infected, 250 mg Inh.2D: Infected, Placebo Inh., Placebo i.v.2D: Infected, 250 mg Inh., Placebo i.v.2D: Infected, 250 mg Inh., 40 mg/kg i.v.
Proportion of Patients With Any AE Within 7 d of Study Drug Administration211310633
SecondaryDZIF-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.

Time frame:
0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose
Reported as:
Geometric mean · μg*h/ml
DZIF-10c Area Under the Curve
μg*h/ml1A: Healthy, 50 mg Inh.1B: Healthy, 100 mg Inh.1C: Healthy, 250 mg Inh.2A: Infected, 50 mg Inh.2B: Infected, 100 mg Inh.2C: Infected, 250 mg Inh.2D: Infected, 250 mg Inh., Placebo i.v.2D: Infected, 250 mg Inh., 40 mg/kg i.v.
DZIF-10c Area Under the CurveNA ± NANA ± NA284 ± 18.2NA ± NA199 ± NANA ± NA225 ± 39.2174000 ± 14.5
SecondaryAnti-Drug Antibody Development

Individuals developing anti-drug antibodies

Time frame:
0, 14, 28, 56, 90 days post dose
Reported as:
Count of participants · Participants
Anti-Drug Antibody Development
Participants1A: Healthy, 50 mg Inh.1B: Healthy, 100 mg Inh.1C: Healthy, 250 mg Inh.2A: Infected, 50 mg Inh.2B: Infected, 100 mg Inh.2C: Infected, 250 mg Inh.2D: Infected, 250 mg Inh., Placebo i.v.2D: Infected, 250 mg Inh., 40 mg/kg i.v.
Anti-Drug Antibody Development00000000
SecondaryTime-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

Time frame:
0, 1, 3, 7, 14, 28 days post dose
Reported as:
Mean · log10 cp/ml
Time-weighted SARS-CoV-2 Viral Load Change From Baseline
log10 cp/ml2D: Infected, Placebo Inh., Placebo i.v.2D: Infected, 250 mg Inh., Placebo i.v.2D: Infected, 250 mg Inh., 40 mg/kg i.v.
Over 7 days-1.932 ± 0.263-2.100 ± 0.294-1.716 ± 0.268
Over 14 days-2.780 ± 0.238-3.044 ± 0.267-2.786 ± 0.244
Over 28 days-3.616 ± 0.126-3.652 ± 0.142-3.652 ± 0.129
SecondaryMMRM 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

Time frame:
0, 1, 3, 7, 14, 28 days post dose
Reported as:
Mean · Adjusted log10 VL (cp/ml)
MMRM SARS-CoV-2 Viral Load Change From Baseline
Adjusted log10 VL (cp/ml)2D: Infected, Placebo Inh., Placebo i.v.2D: Infected, 250 mg Inh., Placebo i.v.2D: Infected, 250 mg Inh., 40 mg/kg i.v.
Over 7 days-3.4 ± 0.4-3.4 ± 0.5-3.2 ± 0.5
Over 14 days-4.4 ± 0.1-4.1 ± 0.1-4.4 ± 0.1
Over 28 days-4.4 ± 0.3-4.3 ± 0.3-4.4 ± 0.3

Adverse events

Collected over 90 days (treatment-emergent adverse events: All adverse events after drug intake until final study visit). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
1A: Healthy, 50 mg Inh.0/3 (0%)0/3 (0%)2/3 (66.7%)
1B: Healthy, 100 mg Inh.0/3 (0%)0/3 (0%)1/3 (33.3%)
1C: Healthy, 250 mg Inh.0/3 (0%)0/3 (0%)2/3 (66.7%)
2A: Infected, 50 mg Inh.0/3 (0%)0/3 (0%)3/3 (100%)
2B: Infected, 100 mg Inh.0/3 (0%)0/3 (0%)2/3 (66.7%)
2C: Infected, 250 mg Inh.0/3 (0%)0/3 (0%)2/3 (66.7%)
2D: Infected, Placebo Inh., Placebo i.v.0/10 (0%)0/10 (0%)7/10 (70%)
2D: Infected, 250 mg Inh., Placebo i.v.0/8 (0%)0/8 (0%)5/8 (62.5%)
2D: Infected, 250 mg Inh., 40 mg/kg i.v.0/9 (0%)0/9 (0%)4/9 (44.4%)
Most frequent other events
Showing 10 of 31
Most frequent other events
Event1A: Healthy, 50 mg Inh.1B: Healthy, 100 mg Inh.1C: Healthy, 250 mg Inh.2A: Infected, 50 mg Inh.2B: Infected, 100 mg Inh.2C: Infected, 250 mg Inh.2D: Infected, Placebo Inh., Placebo i.v.2D: Infected, 250 mg Inh., Placebo i.v.2D: Infected, 250 mg Inh., 40 mg/kg i.v.
ThrombocytopeniaBlood and lymphatic system disorders0/30/30/32/30/30/30/100/80/9
Oropharyngeal painRespiratory, thoracic and mediastinal disorders0/30/30/32/30/30/32/101/80/9
HeadacheNervous system disorders1/30/30/32/30/31/32/102/83/9
CoughRespiratory, thoracic and mediastinal disorders0/31/31/30/30/30/35/102/81/9
InflammationGeneral disorders1/30/30/30/30/30/30/100/80/9
PyrexiaGeneral disorders0/30/30/30/31/30/32/100/80/9
Alanine aminotransferase increasedInvestigations0/30/30/30/30/31/31/100/80/9
Lipase increasedInvestigations0/30/30/31/30/30/30/100/80/9
Ventricular arrhythmiaCardiac disorders1/30/30/30/30/30/30/100/80/9
LeukopeniaBlood and lymphatic system disorders0/30/30/31/30/30/30/100/80/9

Baseline characteristics

Age, Continuous
Age, Continuous(years)1A: Healthy, 50 mg Inh.1B: Healthy, 100 mg Inh.1C: Healthy, 250 mg Inh.2A: Infected, 50 mg Inh.2B: Infected, 100 mg Inh.2C: Infected, 250 mg Inh.2D: Infected, Placebo Inh., Placebo i.v.2D: Infected, 250 mg Inh., Placebo i.v.2D: Infected, 250 mg Inh., 40 mg/kg i.v.Total
Median43 (29 to 44)33 (32 to 44)27 (20 to 29)35 (30 to 62)39 (25 to 42)41 (32 to 46)34 (28 to 36)32 (29 to 46)28 (27 to 38)33 (28 to 42.5)
Sex: Female, Male
Sex: Female, Male(Participants)1A: Healthy, 50 mg Inh.1B: Healthy, 100 mg Inh.1C: Healthy, 250 mg Inh.2A: Infected, 50 mg Inh.2B: Infected, 100 mg Inh.2C: Infected, 250 mg Inh.2D: Infected, Placebo Inh., Placebo i.v.2D: Infected, 250 mg Inh., Placebo i.v.2D: Infected, 250 mg Inh., 40 mg/kg i.v.Total
Female01212122415
Male32121286530
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)1A: Healthy, 50 mg Inh.1B: Healthy, 100 mg Inh.1C: Healthy, 250 mg Inh.2A: Infected, 50 mg Inh.2B: Infected, 100 mg Inh.2C: Infected, 250 mg Inh.2D: Infected, Placebo Inh., Placebo i.v.2D: Infected, 250 mg Inh., Placebo i.v.2D: Infected, 250 mg Inh., 40 mg/kg i.v.Total
Count of participants—————————0
Region of Enrollment
Region of Enrollment(participants)1A: Healthy, 50 mg Inh.1B: Healthy, 100 mg Inh.1C: Healthy, 250 mg Inh.2A: Infected, 50 mg Inh.2B: Infected, 100 mg Inh.2C: Infected, 250 mg Inh.2D: Infected, Placebo Inh., Placebo i.v.2D: Infected, 250 mg Inh., Placebo i.v.2D: Infected, 250 mg Inh., 40 mg/kg i.v.Total
Germany333333108945
08

Study locations

6 sites
  • University Hospital Gießen and Marburg
    Gießen, Hesse 35392, Germany
  • University Hospital Cologne
    Cologne, NRW 50937, Germany
  • University Hospital Düsseldorf
    Düsseldorf, 40225, Germany
  • University Hospital Frankfurt
    Frankfurt am Main, 60590, Germany
  • University Medical Center Hamburg-Eppendorf
    Hamburg, 20246, Germany
  • LMU Munich University Hospital
    Munich, 81377, Germany
09

References and documents

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 ↗
  • 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 ↗

Study documents

  • Study protocol · Apr 1, 2021
  • Statistical analysis plan · May 28, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 3, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04631705
Lead sponsor
University of Cologne
Collaborators
ZKS Köln, Boehringer Ingelheim
Responsible party
Florian Klein (Investigator, University of Cologne) — Principal investigator
First posted
Nov 17, 2020
Start date
Dec 14, 2020
Primary completion
Sep 23, 2021
Completion
Sep 23, 2021
Results posted
Oct 3, 2024
Last update
Oct 3, 2024

Study contacts

Gerd Fätkenheuer, MD
principal investigator · University of Cologne

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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