Clinical trial NCT04631705: SARS-CoV-2-Neutralizing Monoclonal COVID-19 Antibody DZIF-10c by Inhalation
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: SARS-CoV-2 Infection
Keywords: SARS-CoV-2
Covid-19
Monoclonal Antibody
Inhalation
Lead sponsor: University of Cologne
Sponsor class: OTHER
Collaborators: name: ZKS Köln
name: Boehringer Ingelheim
First posted: 2020-11-17
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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).
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of Patients With Any AE Within 7 d of Study Drug Administration
timeFrame: Over first 7 days after study drug administration
Secondary outcomes:
measure: DZIF-10c Area Under the Curve
timeFrame: 0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose
measure: Anti-Drug Antibody Development
timeFrame: 0, 14, 28, 56, 90 days post dose
measure: Time-weighted SARS-CoV-2 Viral Load Change From Baseline
timeFrame: 0, 1, 3, 7, 14, 28 days post dose
measure: MMRM SARS-CoV-2 Viral Load Change From Baseline
timeFrame: 0, 1, 3, 7, 14, 28 days post dose
Other outcomes:
Locations:
city: Gießen
country: Germany
facility: University Hospital Gießen and Marburg
state: Hesse
city: Cologne
country: Germany
facility: University Hospital Cologne
state: NRW
city: Düsseldorf
country: Germany
facility: University Hospital Düsseldorf
city: Frankfurt am Main
country: Germany
facility: University Hospital Frankfurt
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
city: Munich
country: Germany
facility: LMU Munich University Hospital
Study officials:
affiliation: University of Cologne
name: Gerd Fätkenheuer, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.