Clinical trial NCT04631666: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: SARS-CoV-2 Infection
Keywords: SARS-CoV-2
Covid-19
Infusion
Monoclonal Antibody
Lead sponsor: University of Cologne
Sponsor class: OTHER
Collaborators: name: ZKS Köln
name: Boehringer Ingelheim
First posted: 2020-11-17
Enrollment: 57
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 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).
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Proportion of Patients With Any AE Within 7 d of Study Drug Infusion
timeFrame: 7 days
Secondary outcomes:
measure: DZIF-10c Elimination Half Life
timeFrame: 0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose
measure: DZIF-10c Peak Serum Concentration
timeFrame: 0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose
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: DZIF-10c Clearance
timeFrame: 0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose
measure: DZIF-10c Volume of Distribution Vz
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: Anti-Drug Antibody Peak Titer
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: Cologne
country: Germany
facility: University Hospital Cologne
state: NRW
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.