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

Sponsor

University of Cologne (Other)

Overall Status

Completed

CT.gov ID

NCT04631705

Collaborator

ZKS Köln (Other), Boehringer Ingelheim (Industry)

Enrollment

Locations

Arms

9.3

Actual Duration (Months)

7.5

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

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

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

This study consists of an open-label dose escalation phase in both healthy volunteers (Groups 1A-1C) and SARS-CoV-2-infected participants (Groups 2A-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).This study consists of an open-label dose escalation phase in both healthy volunteers (Groups 1A-1C) and SARS-CoV-2-infected participants (Groups 2A-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).

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 14, 2020

Actual Primary Completion Date :

Sep 23, 2021

Actual Study Completion Date :

Sep 23, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1A (uninfected) - low dose SARS-CoV-2-uninfected volunteers will receive a single dose of DZIF-10c by inhalation	Biological: DZIF-10c Inhaled administration of the human monoclonal antibody DZIF-10c
Experimental: Group 1B (uninfected) - mid dose SARS-CoV-2-uninfected volunteers will receive a single dose of DZIF-10c by inhalation	Biological: DZIF-10c Inhaled administration of the human monoclonal antibody DZIF-10c
Experimental: Group 1C (uninfected) - high dose SARS-CoV-2-uninfected volunteers will receive a single dose of DZIF-10c by inhalation	Biological: DZIF-10c Inhaled administration of the human monoclonal antibody DZIF-10c
Experimental: Group 2A (infected) - low dose SARS-CoV-2-infected volunteers will receive a single dose of DZIF-10c by inhalation	Biological: DZIF-10c Inhaled administration of the human monoclonal antibody DZIF-10c
Experimental: Group 2B (infected) - mid dose SARS-CoV-2-infected volunteers will receive a single dose of DZIF-10c by inhalation	Biological: DZIF-10c Inhaled administration of the human monoclonal antibody DZIF-10c
Experimental: Group 2C (infected) - high dose SARS-CoV-2-infected volunteers will receive a single dose of DZIF-10c by inhalation	Biological: DZIF-10c Inhaled administration of the human monoclonal antibody DZIF-10c
Experimental: Group 2D (infected) SARS-CoV-2-infected volunteers will be randomized 1:1:1 to receive DZIF-10c by inhalation and infusion, DZIF-10c by inhalation and placebo by infusion, or placebo by inhalation and infusion	Biological: DZIF-10c Inhaled administration of the human monoclonal antibody DZIF-10c Biological: DZIF-10c Intravenous administration of the human monoclonal antibody DZIF-10c Drug: Placebo Inhalation of DZIF-10c diluent as placebo Drug: 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 inhalation [Safety and Tolerability] [3 months]
Primary target variables are (S)AEs and Adverse Events of Special Interest (AESIs)
Rate of Adverse Events after a single combined DZIF-10c inhalation and infusion [Safety and Tolerability] [3 months]
Primary target variables are (S)AEs and Adverse Events of Special Interest (AESIs)

Secondary Outcome Measures

Pharmacokinetic parameter AUC0-672 [0 to 672 hours]
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
Development of anti-drug antibodies [3 months]
Frequency of the development of anti-drug antibodies targeting DZIF-10c determined by immunoassay
Development of anti-drug antibodies [3 months]
Titer of anti-drug antibodies targeting DZIF-10c determined by immunoassay
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-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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Gießen and Marburg	Gießen	Hesse	Germany	35392
2	University Hospital Cologne	Cologne	NRW	Germany	50937
3	University Hospital Düsseldorf	Düsseldorf		Germany	40225
4	University Hospital Frankfurt	Frankfurt am Main		Germany	60590
5	University Medical Center Hamburg-Eppendorf	Hamburg		Germany	20246
6	LMU Munich University Hospital	Munich		Germany	81377