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

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

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04631666

Enrollment

Registered

2020-11-17

Start date

2020-12-08

Completion date

2021-08-11

Last updated

2024-04-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

SARS-CoV-2 Infection

Keywords

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

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.

Interventions

BIOLOGICALDZIF-10c

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

OTHERPlacebo

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

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

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).

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame
Proportion of Patients With Any AE Within 7 d of Study Drug Infusion	7 days

Secondary

Measure	Time frame	Description
DZIF-10c Peak Serum Concentration	0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose	—
DZIF-10c Area Under the Curve	0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose	Area under the curve based on serum antibody levels
DZIF-10c Clearance	0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose	—
DZIF-10c Volume of Distribution Vz	0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose	—
DZIF-10c Elimination Half Life	0, 1, and 4 hours post dose; 1, 3, 7, 14, 21, 28, 56, 90 days post dose	DZIF-10c serum elimination half-life
Anti-Drug Antibody Peak Titer	0, 14, 28, 56, 90 days post dose	Magnitude of the development of anti-drug antibodies targeting DZIF-10c in individuals developing such antibodies (peak serum titer)
Time-weighted SARS-CoV-2 Viral Load Change From Baseline	0, 1, 3, 7, 14, 28 days post dose	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
MMRM SARS-CoV-2 Viral Load Change From Baseline	0, 1, 3, 7, 14, 28 days post dose	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
Anti-Drug Antibody Development	0, 14, 28, 56, 90 days post dose	Individuals developing anti-drug antibodies

Countries

Germany

Participant flow

Participants by arm

Arm	Count
1A: Healthy, 2.5 mg/kg Open label, SARS-CoV-2 negative, DZIF-10c i.v. infusion	3
1B: Healthy, 10 mg/kg Open label, SARS-CoV-2 negative, DZIF-10c i.v. infusion	3
1C: Healthy, 40 mg/kg Open label, SARS-CoV-2 negative, DZIF-10c i.v. infusion	3
1D: Healthy, 80 mg/kg Open label, SARS-CoV-2 negative, DZIF-10c i.v. infusion	6
2C: Infected, 40 mg/kg Open label, SARS-CoV-2-infected, DZIF-10c i.v. infusion	3
2D: Infected, 40 mg/kg Double-blind and randomized, SARS-CoV-2-infected, DZIF-10c i.v. infusion	26
2D: Infected, Placebo Double-blind and randomized, SARS-CoV-2-infected, placebo i.v. infusion	13
Total	57

Baseline characteristics

Characteristic	1A: Healthy, 2.5 mg/kg	1B: Healthy, 10 mg/kg	1C: Healthy, 40 mg/kg	1D: Healthy, 80 mg/kg	2C: Infected, 40 mg/kg	2D: Infected, 40 mg/kg	2D: Infected, Placebo	Total
Age, Continuous	26 years	28 years	28 years	26.5 years	43 years	40 years	32 years	32 years
Race and Ethnicity Not Collected	—	—	—	—	—	—	—	0 Participants
Region of Enrollment Germany	3 Participants	3 Participants	3 Participants	6 Participants	3 Participants	26 Participants	13 Participants	57 Participants
Sex: Female, Male Female	0 Participants	3 Participants	1 Participants	5 Participants	2 Participants	11 Participants	5 Participants	27 Participants
Sex: Female, Male Male	3 Participants	0 Participants	2 Participants	1 Participants	1 Participants	15 Participants	8 Participants	30 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk
deaths Total, all-cause mortality	0 / 3	0 / 3	0 / 3	0 / 6	0 / 3	0 / 26	0 / 13
other Total, other adverse events	2 / 3	1 / 3	2 / 3	0 / 6	1 / 3	18 / 26	10 / 13
serious Total, serious adverse events	0 / 3	0 / 3	0 / 3	0 / 6	0 / 3	0 / 26	0 / 13

Outcome results

Primary

Proportion of Patients With Any AE Within 7 d of Study Drug Infusion

Time frame: 7 days

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
1A: Healthy, 2.5 mg/kg	Proportion of Patients With Any AE Within 7 d of Study Drug Infusion	2 Participants
1B: Healthy, 10 mg/kg	Proportion of Patients With Any AE Within 7 d of Study Drug Infusion	1 Participants
1C: Healthy, 40 mg/kg	Proportion of Patients With Any AE Within 7 d of Study Drug Infusion	0 Participants
1D: Healthy, 80 mg/kg	Proportion of Patients With Any AE Within 7 d of Study Drug Infusion	0 Participants
2C: Infected, 40 mg/kg	Proportion of Patients With Any AE Within 7 d of Study Drug Infusion	0 Participants
2D: Infected, 40 mg/kg	Proportion of Patients With Any AE Within 7 d of Study Drug Infusion	11 Participants
2D: Infected, Placebo	Proportion of Patients With Any AE Within 7 d of Study Drug Infusion	8 Participants

Secondary

Anti-Drug Antibody Development

Individuals developing anti-drug antibodies

Time frame: 0, 14, 28, 56, 90 days post dose

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
1A: Healthy, 2.5 mg/kg	Anti-Drug Antibody Development	0 Participants
1B: Healthy, 10 mg/kg	Anti-Drug Antibody Development	0 Participants
1C: Healthy, 40 mg/kg	Anti-Drug Antibody Development	0 Participants
1D: Healthy, 80 mg/kg	Anti-Drug Antibody Development	0 Participants
2C: Infected, 40 mg/kg	Anti-Drug Antibody Development	1 Participants
2D: Infected, 40 mg/kg	Anti-Drug Antibody Development	0 Participants

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)

Time frame: 0, 14, 28, 56, 90 days post dose

Arm	Measure	Value (NUMBER)
1A: Healthy, 2.5 mg/kg	Anti-Drug Antibody Peak Titer	960 reciprocal serum titer

Secondary