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Change in viral variant epidemiology
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| Name | Class |
|---|---|
| ZKS Köln | OTHER |
| Boehringer Ingelheim | INDUSTRY |
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1A (uninfected) - low dose | Experimental | SARS-CoV-2-uninfected volunteers will receive a single dose of DZIF-10c by inhalation |
|
| Group 1B (uninfected) - mid dose | Experimental | SARS-CoV-2-uninfected volunteers will receive a single dose of DZIF-10c by inhalation |
|
| Group 1C (uninfected) - high dose | Experimental | SARS-CoV-2-uninfected volunteers will receive a single dose of DZIF-10c by inhalation |
|
| Group 2A (infected) - low dose | Experimental | SARS-CoV-2-infected volunteers will receive a single dose of DZIF-10c by inhalation |
|
| Group 2B (infected) - mid dose | Experimental | SARS-CoV-2-infected volunteers will receive a single dose of DZIF-10c by inhalation |
|
| Group 2C (infected) - high dose |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DZIF-10c | Biological | Inhaled administration of the human monoclonal antibody DZIF-10c |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Patients With Any AE Within 7 d of Study Drug Administration | Over first 7 days after study drug administration |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose |
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Inclusion Criteria:
Groups 1A-1C
Groups 2A-2D
Exclusion Criteria (all groups):
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| Name | Affiliation | Role |
|---|---|---|
| Gerd Fätkenheuer, MD | University of Cologne | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Gießen and Marburg | Giessen | Hesse | 35392 | Germany | ||
| University Hospital Cologne |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32946786 | Background | 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. | |
| 34473343 |
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| ID | Title | Description |
|---|---|---|
| FG000 | 1A: Healthy, 50 mg Inh. | Open label, SARS-CoV-2 negative, DZIF-10c dose administered by inhalation |
| FG001 | 1B: Healthy, 100 mg Inh. | Open label, SARS-CoV-2 negative, DZIF-10c dose administered by inhalation |
| FG002 | 1C: Healthy, 250 mg Inh. | Open label, SARS-CoV-2 negative, DZIF-10c dose administered by inhalation |
| FG003 | 2A: Infected, 50 mg Inh. | Open label, SARS-CoV-2-infected, DZIF-10c dose administered by inhalation |
| FG004 | 2B: Infected, 100 mg Inh. | Open label, SARS-CoV-2-infected, DZIF-10c dose administered by inhalation |
| FG005 | 2C: Infected, 250 mg Inh. | Open label, SARS-CoV-2-infected, DZIF-10c dose administered by inhalation |
| FG006 | 2D: Infected, Placebo Inh., Placebo i.v. | Double blind and randomized, SARS-CoV-2-infected, placebo by inhalation, placebo by i.v. infusion |
| FG007 | 2D: Infected, 250 mg Inh., Placebo i.v. | Double blind and randomized, SARS-CoV-2-infected, DZIF-10c by inhalation, placebo by i.v. infusion |
| FG008 | 2D: Infected, 250 mg Inh., 40 mg/kg i.v. | Double blind and randomized, SARS-CoV-2-infected, DZIF-10c by inhalation, DZIF-10c by i.v. infusion |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | 1A: Healthy, 50 mg Inh. | Open label, SARS-CoV-2 negative, DZIF-10c dose administered by inhalation |
| BG001 | 1B: Healthy, 100 mg Inh. | Open label, SARS-CoV-2 negative, DZIF-10c dose administered by inhalation |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Proportion of Patients With Any AE Within 7 d of Study Drug Administration | Posted | Count of Participants | Participants | Over first 7 days after study drug administration |
|
90 days (treatment-emergent adverse events: All adverse events after drug intake until final study visit)
Participants were queried about potential Adverse Events at all study visits.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 1A: Healthy, 50 mg Inh. | Open label, SARS-CoV-2 negative, DZIF-10c dose administered by inhalation |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypersensitivity | Immune system disorders | Systematic Assessment |
- Small sample size, further reduced by early termination
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof. Florian Klein | Institute of Virology | 49221478 | 85800 | florian.klein@uk-koeln.de |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 1, 2021 | Dec 6, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 28, 2021 | Dec 6, 2022 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D053120 | Respiratory Aspiration |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C000715848 | BI 767551 |
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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).
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SARS-CoV-2-infected volunteers will receive a single dose of DZIF-10c by inhalation |
|
| 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 |
|
| DZIF-10c | Biological | Intravenous administration of the human monoclonal antibody DZIF-10c |
|
| Placebo | Drug | Inhalation of DZIF-10c diluent as placebo |
|
| Placebo | Drug | Intravenous infusion of sterile normal saline (NaCl 0.9%) as placebo |
|
| Anti-Drug Antibody Development | Individuals developing anti-drug antibodies | 0, 14, 28, 56, 90 days post dose |
| 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 | 0, 1, 3, 7, 14, 28 days post dose |
| 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 | 0, 1, 3, 7, 14, 28 days post dose |
| Cologne |
| North Rhine-Westphalia |
| 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 |
| Derived |
| 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. |
| BG002 | 1C: Healthy, 250 mg Inh. | Open label, SARS-CoV-2 negative, DZIF-10c dose administered by inhalation |
| BG003 | 2A: Infected, 50 mg Inh. | Open label, SARS-CoV-2-infected, DZIF-10c dose administered by inhalation |
| BG004 | 2B: Infected, 100 mg Inh. | Open label, SARS-CoV-2-infected, DZIF-10c dose administered by inhalation |
| BG005 | 2C: Infected, 250 mg Inh. | Open label, SARS-CoV-2-infected, DZIF-10c dose administered by inhalation |
| BG006 | 2D: Infected, Placebo Inh., Placebo i.v. | Double blind and randomized, SARS-CoV-2-infected, placebo by inhalation, placebo by i.v. infusion |
| BG007 | 2D: Infected, 250 mg Inh., Placebo i.v. | Double blind and randomized, SARS-CoV-2-infected, DZIF-10c by inhalation, placebo by i.v. infusion |
| BG008 | 2D: Infected, 250 mg Inh., 40 mg/kg i.v. | Double blind and randomized, SARS-CoV-2-infected, DZIF-10c by inhalation, DZIF-10c by i.v. infusion |
| BG009 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG003 | 2A: Infected, 50 mg Inh. | Open label, SARS-CoV-2-infected, DZIF-10c dose administered by inhalation |
| OG004 | 2B: Infected, 100 mg Inh. | Open label, SARS-CoV-2-infected, DZIF-10c dose administered by inhalation |
| OG005 | 2C: Infected, 250 mg Inh. | Open label, SARS-CoV-2-infected, DZIF-10c dose administered by inhalation |
| OG006 | 2D: Infected, Placebo Inh., Placebo i.v. | Double blind and randomized, SARS-CoV-2-infected, placebo by inhalation, placebo by i.v. infusion |
| OG007 | 2D: Infected, 250 mg Inh., Placebo i.v. | Double blind and randomized, SARS-CoV-2-infected, DZIF-10c by inhalation, placebo by i.v. infusion |
| OG008 | 2D: Infected, 250 mg Inh., 40 mg/kg i.v. | Double blind and randomized, SARS-CoV-2-infected, DZIF-10c by inhalation, DZIF-10c by i.v. infusion |
|
|
| Secondary | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | μg*h/ml | 0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose |
|
|
|
| Secondary | Anti-Drug Antibody Development | Individuals developing anti-drug antibodies | Posted | Count of Participants | Participants | 0, 14, 28, 56, 90 days post dose |
|
|
|
| Secondary | 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 | Posted | Mean | Standard Error | log10 cp/ml | 0, 1, 3, 7, 14, 28 days post dose |
|
|
|
| Secondary | 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 | Posted | Mean | Standard Error | Adjusted log10 VL (cp/ml) | 0, 1, 3, 7, 14, 28 days post dose |
|
|
|
| 0 |
| 3 |
| 0 |
| 3 |
| 2 |
| 3 |
| EG001 | 1B: Healthy, 100 mg Inh. | Open label, SARS-CoV-2 negative, DZIF-10c dose administered by inhalation | 0 | 3 | 0 | 3 | 1 | 3 |
| EG002 | 1C: Healthy, 250 mg Inh. | Open label, SARS-CoV-2 negative, DZIF-10c dose administered by inhalation | 0 | 3 | 0 | 3 | 2 | 3 |
| EG003 | 2A: Infected, 50 mg Inh. | Open label, SARS-CoV-2-infected, DZIF-10c dose administered by inhalation | 0 | 3 | 0 | 3 | 3 | 3 |
| EG004 | 2B: Infected, 100 mg Inh. | Open label, SARS-CoV-2-infected, DZIF-10c dose administered by inhalation | 0 | 3 | 0 | 3 | 2 | 3 |
| EG005 | 2C: Infected, 250 mg Inh. | Open label, SARS-CoV-2-infected, DZIF-10c dose administered by inhalation | 0 | 3 | 0 | 3 | 2 | 3 |
| EG006 | 2D: Infected, Placebo Inh., Placebo i.v. | Double blind and randomized, SARS-CoV-2-infected, placebo by inhalation, placebo by i.v. infusion | 0 | 10 | 0 | 10 | 7 | 10 |
| EG007 | 2D: Infected, 250 mg Inh., Placebo i.v. | Double blind and randomized, SARS-CoV-2-infected, DZIF-10c by inhalation, placebo by i.v. infusion | 0 | 8 | 0 | 8 | 5 | 8 |
| EG008 | 2D: Infected, 250 mg Inh., 40 mg/kg i.v. | Double blind and randomized, SARS-CoV-2-infected, DZIF-10c by inhalation, DZIF-10c by i.v. infusion | 0 | 9 | 0 | 9 | 4 | 9 |
| Inflammation | General disorders | Systematic Assessment |
|
| Pyrexia | General disorders | Systematic Assessment |
|
| Pain | General disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Chest pain | General disorders | Systematic Assessment |
|
| Aphasia | Psychiatric disorders | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | Systematic Assessment |
|
| Lipase increased | Investigations | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
|
| Ventricular arrhythmia | Cardiac disorders | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Sciatica | Nervous system disorders | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | Systematic Assessment |
|
| Disturbance in attention | Nervous system disorders | Systematic Assessment |
|
| Parosmia | Nervous system disorders | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Sinusitis | Infections and infestations | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | Systematic Assessment |
|
| Gonococcal infection | Infections and infestations | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | Systematic Assessment |
|
Publications by PIs are to be submitted to the sponsor for review at least 30 days prior to planned disclosure. Modifications suggested by the sponsor should be considered unless they affect the scientific character or neutrality of the publication. A maximum embargo period of 90 days is applicable only if disclosure would affect (potential) intellectual property rights.
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Male |
|
|
| Over 28 days |
|
|
| Over 28 days |
|