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

SARS-CoV-2 Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04631666
• Other study ID #: Uni-Koeln-4288
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 8, 2020
• Est. completion date: August 11, 2021

Study information

• Verified date: October 2023
• 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: August 11, 2021
• Est. primary completion date: August 11, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• SARS-CoV-2 Infection

Intervention

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

Locations

Country	Name	City	State
Germany	University Hospital Cologne	Cologne	NRW

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, 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients With Any AE Within 7 d of Study Drug Infusion		7 days
Secondary	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
Secondary	DZIF-10c Peak Serum Concentration		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	0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose
Secondary	DZIF-10c Clearance		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		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	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)	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	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	0, 1, 3, 7, 14, 28 days post dose