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

Sponsor

University of Cologne (Other)

Overall Status

Completed

CT.gov ID

NCT04631666

Collaborator

ZKS Köln (Other), Boehringer Ingelheim (Industry)

Enrollment

Location

Arms

8.1

Actual Duration (Months)

7.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
SARS-CoV-2 Infection	Biological: DZIF-10c Other: Placebo	Phase 1/Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

57 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention 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).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 (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 8, 2020

Actual Primary Completion Date :

Aug 11, 2021

Actual Study Completion Date :

Aug 11, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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