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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase 1/2a Trial of the Intravenous Administration of the SARS-CoV-2-Neutralizing Monoclonal Antibody DZIF-10c in SARS-CoV-2-Infected and -Uninfected Individuals

Conditions
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SARS-CoV-2 Infection

Intervention / Treatment
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* Biological: DZIF-10c
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Groups 1A-1D 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 2C-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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: 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).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1A (uninfected) - 2.5 mg/kg<br>SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 2.5 mg/kg | Biological: DZIF-10c<br>* SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion<br>|
| Experimental: Group 1B (uninfected) - 10 mg/kg<br>SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 10 mg/kg | Biological: DZIF-10c<br>* SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion<br>|
| Experimental: Group 1C (uninfected) - 40 mg/kg<br>SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 40 mg/kg | Biological: DZIF-10c<br>* SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion<br>|
| Experimental: Group 1D (uninfected) - high dose<br>SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose higher than 40 mg/kg | Biological: DZIF-10c<br>* SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion<br>|
| Experimental: Group 2C (infected) - 40 mg/kg<br>SARS-CoV-2-infected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 40 mg/kg | Biological: DZIF-10c<br>* SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion<br>|
| Experimental: Group 2D (infected) - 40 mg/kg<br>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 | Biological: DZIF-10c<br>* SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion<br>Other: Placebo<br>* Intravenous infusion of sterile normal saline (NaCl 0.9%) as placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Adverse Events after a single DZIF-10c infusion [Safety and Tolerability] | Primary target variables are (S)AEs and Adverse Events of Special Interest (AESIs) | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile of DZIF-10c | Elimination half-life (t1/2) of DZIF-10c | 3 months | 
| Pharmacokinetic profile of DZIF-10c | Peak serum concentration (Cmax) of DZIF-10c | 3 months | 
| Pharmacokinetic profile of DZIF-10c | Area under the curve (AUC) | 3 months | 
| Pharmacokinetic profile of DZIF-10c | Clearance (CL/F) of DZIF-10c | 3 months | 
| Pharmacokinetic profile of DZIF-10c | Volume of distribution (Vz/F) of DZIF-10c | 3 months | 
| Development of anti-drug antibodies | Frequency of the development of anti-drug antibodies targeting DZIF-10c | 3 months | 
| Development of anti-drug antibodies | Magnitude of the development of anti-drug antibodies targeting DZIF-10c | 3 months | 
| Change in viral load in nasopharyngeal swabs after DZIF-10c administration | Change in SARS-CoV-2 RNA from baseline in nasopharyngeal swabs as determined by qRT-pCR | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, Covid-19, Infusion, Monoclonal Antibody