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

SARS-CoV-2 Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04631705
• Other study ID #: Uni-Koeln-4370
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 14, 2020
• Est. completion date: September 23, 2021

Study information

• Verified date: October 2021
• Source: University of Cologne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: September 23, 2021
• Est. primary completion date: September 23, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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 (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

Related Conditions & MeSH terms

• COVID-19
• SARS-CoV-2 Infection

Intervention

Biological:
• DZIF-10c
Inhaled administration of the human monoclonal antibody DZIF-10c
• DZIF-10c
Intravenous administration of the human monoclonal antibody DZIF-10c

Drug:
• Placebo
Inhalation of DZIF-10c diluent as placebo
• Placebo
Intravenous infusion of sterile normal saline (NaCl 0.9%) as placebo

Locations

Country	Name	City	State
Germany	University Hospital Cologne	Cologne	NRW
Germany	University Hospital Düsseldorf	Düsseldorf
Germany	University Hospital Frankfurt	Frankfurt am Main
Germany	University Hospital Gießen and Marburg	Gießen	Hesse
Germany	University Medical Center Hamburg-Eppendorf	Hamburg
Germany	LMU Munich University Hospital	Munich

Sponsors (3)

Lead Sponsor	Collaborator
University of Cologne	Boehringer Ingelheim, ZKS Köln

Country where clinical trial is conducted

Germany, 

References & Publications (1)

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, Krähling 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Adverse Events after a single DZIF-10c inhalation [Safety and Tolerability]	Primary target variables are (S)AEs and Adverse Events of Special Interest (AESIs)	3 months
Primary	Rate of Adverse Events after a single combined DZIF-10c inhalation and infusion [Safety and Tolerability]	Primary target variables are (S)AEs and Adverse Events of Special Interest (AESIs)	3 months
Secondary	Pharmacokinetic parameter AUC0-672	AUC0-672 (the area under the concentration-time curve of DZIF-10c in serum over the time interval from 0 to 672 hours (Day 28)) after inhaled and combined inhaled and intravenous application	0 to 672 hours
Secondary	Development of anti-drug antibodies	Frequency of the development of anti-drug antibodies targeting DZIF-10c determined by immunoassay	3 months
Secondary	Development of anti-drug antibodies	Titer of anti-drug antibodies targeting DZIF-10c determined by immunoassay	3 months
Secondary	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