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

Primary Purpose

SARS-CoV-2 Infection

Status

Completed

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

DZIF-10c

Placebo

About this trial

This is an interventional treatment trial for SARS-CoV-2 Infection focused on measuring SARS-CoV-2, Covid-19, Infusion, Monoclonal Antibody

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

University Hospital Cologne

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

Group 1A (uninfected) - 2.5 mg/kg

Group 1B (uninfected) - 10 mg/kg

Group 1C (uninfected) - 40 mg/kg

Group 1D (uninfected) - high dose

Group 2C (infected) - 40 mg/kg

Group 2D (infected) - 40 mg/kg

Arm Description

SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 2.5 mg/kg

SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 10 mg/kg

SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 40 mg/kg

SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose higher than 40 mg/kg

SARS-CoV-2-infected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Pharmacokinetic profile of DZIF-10c

Elimination half-life (t1/2) of DZIF-10c

Pharmacokinetic profile of DZIF-10c

Peak serum concentration (Cmax) of DZIF-10c

Pharmacokinetic profile of DZIF-10c

Area under the curve (AUC)

Pharmacokinetic profile of DZIF-10c

Clearance (CL/F) of DZIF-10c

Pharmacokinetic profile of DZIF-10c

Volume of distribution (Vz/F) of DZIF-10c

Development of anti-drug antibodies

Frequency of the development of anti-drug antibodies targeting DZIF-10c

Development of anti-drug antibodies

Magnitude of the development of anti-drug antibodies targeting DZIF-10c

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

Full Information

NCT ID

NCT04631666

First Posted

November 5, 2020

Last Updated

August 22, 2021

Sponsor

University of Cologne

Collaborators

ZKS Köln, Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT04631666

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Completed

Study Start Date

December 8, 2020 (Actual)

Primary Completion Date

August 11, 2021 (Actual)

Study Completion Date

August 11, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Cologne

Collaborators

ZKS Köln, Boehringer Ingelheim

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

SARS-CoV-2 Infection

Keywords

SARS-CoV-2, Covid-19, Infusion, Monoclonal Antibody

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

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

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

57 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1A (uninfected) - 2.5 mg/kg

Arm Type

Experimental

Arm Description

SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 2.5 mg/kg

Arm Title

Group 1B (uninfected) - 10 mg/kg

Arm Type

Experimental

Arm Description

SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 10 mg/kg

Arm Title

Group 1C (uninfected) - 40 mg/kg

Arm Type

Experimental

Arm Description

SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 40 mg/kg

Arm Title

Group 1D (uninfected) - high dose

Arm Type

Experimental

Arm Description

SARS-CoV-2-uninfected volunteers will receive a single intravenous infusion of DZIF-10c at a dose higher than 40 mg/kg

Arm Title

Group 2C (infected) - 40 mg/kg

Arm Type

Experimental

Arm Description

SARS-CoV-2-infected volunteers will receive a single intravenous infusion of DZIF-10c at a dose of 40 mg/kg

Arm Title

Group 2D (infected) - 40 mg/kg

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

DZIF-10c

Intervention Description

SARS-CoV-2-neutralizing monoclonal antibody DZIF-10c by intravenous infusion

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Intravenous infusion of sterile normal saline (NaCl 0.9%) as placebo

Primary Outcome Measure Information:

Title

Rate of Adverse Events after a single DZIF-10c infusion [Safety and Tolerability]

Description

Primary target variables are (S)AEs and Adverse Events of Special Interest (AESIs)

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Pharmacokinetic profile of DZIF-10c

Description

Elimination half-life (t1/2) of DZIF-10c

Time Frame

3 months

Title

Pharmacokinetic profile of DZIF-10c

Description

Peak serum concentration (Cmax) of DZIF-10c

Time Frame

3 months

Title

Pharmacokinetic profile of DZIF-10c

Description

Area under the curve (AUC)

Time Frame

3 months

Title

Pharmacokinetic profile of DZIF-10c

Description

Clearance (CL/F) of DZIF-10c

Time Frame

3 months

Title

Pharmacokinetic profile of DZIF-10c

Description

Volume of distribution (Vz/F) of DZIF-10c

Time Frame

3 months

Title

Development of anti-drug antibodies

Description

Frequency of the development of anti-drug antibodies targeting DZIF-10c

Time Frame

3 months

Title

Development of anti-drug antibodies

Description

Magnitude of the development of anti-drug antibodies targeting DZIF-10c

Time Frame

3 months

Title

Change in viral load in nasopharyngeal swabs after DZIF-10c administration

Description

Change in SARS-CoV-2 RNA from baseline in nasopharyngeal swabs as determined by qRT-pCR

Time Frame

28 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gerd Fätkenheuer, MD

Organizational Affiliation

University of Cologne

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospital Cologne

City

Cologne

State/Province

NRW

ZIP/Postal Code

50937

Country

Germany

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

32946786

Citation

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.

Results Reference

background

PubMed Identifier

34473343

Citation

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.

Results Reference

derived

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

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