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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 intravenous 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 intravenous infusion open-label dose-escalation phase (Groups 1A-1D and Group 2C). Subsequently, the highest tested and tolerated dose 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 by intravenous infusion.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1A (uninfected) - 2.5 mg/kg | Experimental | SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 2.5 mg/kg |
|
| Group 1B (uninfected) - 10 mg/kg | Experimental | SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 10 mg/kg |
|
| Group 1C (uninfected) - 40 mg/kg | Experimental | SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 40 mg/kg |
|
| Group 1D (uninfected) - high dose | Experimental | SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose higher than 40 mg/kg |
|
| Group 2C (infected) - 40 mg/kg | Experimental | SARS-CoV-2-infected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 40 mg/kg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DZIF-10c | Biological | SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Patients With Any AE Within 7 d of Study Drug Infusion | 7 days |
| Measure | Description | Time Frame |
|---|---|---|
| DZIF-10c Elimination Half Life | DZIF-10c serum elimination half-life | 0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose |
| DZIF-10c Peak Serum Concentration | 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-1D
Groups 2C-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 Cologne | Cologne | North Rhine-Westphalia | 50937 | Germany |
| 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, 2.5 mg/kg | Open label, SARS-CoV-2 negative, DZIF-10c i.v. infusion |
| FG001 | 1B: Healthy, 10 mg/kg | Open label, SARS-CoV-2 negative, DZIF-10c i.v. infusion |
| FG002 | 1C: Healthy, 40 mg/kg | Open label, SARS-CoV-2 negative, DZIF-10c i.v. infusion |
| FG003 | 1D: Healthy, 80 mg/kg | Open label, SARS-CoV-2 negative, DZIF-10c i.v. infusion |
| FG004 | 2C: Infected, 40 mg/kg | Open label, SARS-CoV-2-infected, DZIF-10c i.v. infusion |
| FG005 | 2D: Infected, 40 mg/kg | Double-blind and randomized, SARS-CoV-2-infected, DZIF-10c i.v. infusion |
| FG006 | 2D: Infected, Placebo | Double-blind and randomized, SARS-CoV-2-infected, placebo i.v. infusion |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 1A: Healthy, 2.5 mg/kg | Open label, SARS-CoV-2 negative, DZIF-10c i.v. infusion |
| BG001 | 1B: Healthy, 10 mg/kg | Open label, SARS-CoV-2 negative, DZIF-10c i.v. infusion |
| 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 Infusion | Posted | Count of Participants | Participants | 7 days |
|
Treatment-emergent adverse events: All adverse events after drug intake until final study visit (Day 90 visit)
Participants were queried for 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, 2.5 mg/kg | SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 2.5 mg/kg DZIF-10c: SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Flushing | Vascular disorders | Systematic Assessment |
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| 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 7, 2021 | Dec 6, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 20, 2021 | Dec 6, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| 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 healthy volunteers (Groups 1A-1C) and an additional open-label lead-in phase in SARS-CoV-2-infected individuals (Group 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).
An additional higher dose cohort may be included for healthy volunteers (Group 1D).
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| Group 2D (infected) - 40 mg/kg |
| Experimental |
SARS-CoV-2-infected volunteers will be randomized 2:1 to receive an intravenous infusion of DZIF-10c at a dose of 40 mg/kg or placebo |
|
| Placebo | Other | Intravenous infusion of sterile normal saline (NaCl 0.9%) as placebo |
|
| DZIF-10c Area Under the Curve | Area under the curve based on serum antibody levels | 0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose |
| DZIF-10c Clearance | 0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose |
| DZIF-10c Volume of Distribution Vz | 0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose |
| Anti-Drug Antibody Development | Individuals developing anti-drug antibodies | 0, 14, 28, 56, 90 days post dose |
| Anti-Drug Antibody Peak Titer | Magnitude of the development of anti-drug antibodies targeting DZIF-10c in individuals developing such antibodies (peak serum titer) | 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 |
| 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, 40 mg/kg | Open label, SARS-CoV-2 negative, DZIF-10c i.v. infusion |
| BG003 | 1D: Healthy, 80 mg/kg | Open label, SARS-CoV-2 negative, DZIF-10c i.v. infusion |
| BG004 | 2C: Infected, 40 mg/kg | Open label, SARS-CoV-2-infected, DZIF-10c i.v. infusion |
| BG005 | 2D: Infected, 40 mg/kg | Double-blind and randomized, SARS-CoV-2-infected, DZIF-10c i.v. infusion |
| BG006 | 2D: Infected, Placebo | Double-blind and randomized, SARS-CoV-2-infected, placebo i.v. infusion |
| BG007 | 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 | Count of Participants | Participants |
|
| OG003 |
| 1D: Healthy, 80 mg/kg |
Open label, SARS-CoV-2 negative, DZIF-10c i.v. infusion |
| OG004 | 2C: Infected, 40 mg/kg | Open label, SARS-CoV-2-infected, DZIF-10c i.v. infusion |
| OG005 | 2D: Infected, 40 mg/kg | Double-blind and randomized, SARS-CoV-2-infected, DZIF-10c i.v. infusion |
| OG006 | 2D: Infected, Placebo | Double-blind and randomized, SARS-CoV-2-infected, placebo i.v. infusion |
|
|
| Secondary | DZIF-10c Elimination Half Life | DZIF-10c serum elimination half-life | Posted | Geometric Mean | Geometric Coefficient of Variation | days | 0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose |
|
|
|
| Secondary | DZIF-10c Peak Serum Concentration | Posted | Geometric Mean | Geometric Coefficient of Variation | µg/ml | 0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose |
|
|
|
| Secondary | DZIF-10c Area Under the Curve | Area under the curve based on serum antibody levels | 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 | DZIF-10c Clearance | Posted | Geometric Mean | Geometric Coefficient of Variation | ml/day | 0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose |
|
|
|
| Secondary | DZIF-10c Volume of Distribution Vz | Posted | Geometric Mean | Geometric Coefficient of Variation | 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 | Anti-Drug Antibody Peak Titer | Magnitude of the development of anti-drug antibodies targeting DZIF-10c in individuals developing such antibodies (peak serum titer) | Posted | Number | reciprocal serum titer | 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 cp/ml | 0, 1, 3, 7, 14, 28 days post dose |
|
|
|
| 0 |
| 3 |
| 0 |
| 3 |
| 2 |
| 3 |
| EG001 | 1B: Healthy, 10 mg/kg | SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 10 mg/kg DZIF-10c: SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion | 0 | 3 | 0 | 3 | 1 | 3 |
| EG002 | 1C: Healthy, 40 mg/kg | SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 40 mg/kg DZIF-10c: SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion | 0 | 3 | 0 | 3 | 2 | 3 |
| EG003 | 1D: Healthy, 80 mg/kg | SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose higher than 40 mg/kg DZIF-10c: SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion | 0 | 6 | 0 | 6 | 0 | 6 |
| EG004 | 2C: Infected, 40 mg/kg | SARS-CoV-2-infected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 40 mg/kg DZIF-10c: SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion | 0 | 3 | 0 | 3 | 1 | 3 |
| EG005 | 2D: Infected, 40 mg/kg | SARS-CoV-2-infected volunteers randomized to receive an intravenous infusion of DZIF-10c at a dose of 40 mg/kg (blinded) DZIF-10c: SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion | 0 | 26 | 0 | 26 | 18 | 26 |
| EG006 | 2D: Infected, Placebo | SARS-CoV-2-infected volunteers randomized to receive an intravenous infusion of placebo (blinded) Placebo: Sterile normal saline | 0 | 13 | 0 | 13 | 10 | 13 |
| Hypertension | Vascular disorders | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Hyposmia | Nervous system disorders | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | Systematic Assessment |
|
| Disturbance in attention | Nervous system disorders | Systematic Assessment |
|
| Hypogeusia | Nervous system disorders | Systematic Assessment |
|
| Parosmia | Nervous system disorders | Systematic Assessment |
|
| Ageusia | Nervous system disorders | Systematic Assessment |
|
| Pain | General disorders | Systematic Assessment |
|
| Chest discomfort | General disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | Systematic Assessment |
|
| Pyrexia | General disorders | Systematic Assessment |
|
| Malaise | General disorders | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | Systematic Assessment |
|
| Tympanic membrane perforation | Ear and labyrinth disorders | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | Systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Thyroid mass | Endocrine disorders | Systematic Assessment |
|
| COVID-19 | Infections and infestations | Systematic Assessment |
|
| Rhinitis | Infections and infestations | Systematic Assessment |
|
| Cystitis | Infections and infestations | Systematic Assessment |
|
| Tonsillitis | Infections and infestations | Systematic Assessment |
|
| Tooth abscess | Infections and infestations | Systematic Assessment |
|
| Palpitations | Cardiac disorders | 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 |
| Male |
|
| Over 28 days |
|
| Over 28 days |
|