Clinical Trials Register

Summary
EudraCT Number:	2020-004448-27
Sponsor's Protocol Code Number:	Uni-Koeln-4370
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-11-18
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2020-004448-27

A.3

Full title of the trial

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

Eine Phase-1/2a-Studie zur inhalativen Verabreichung des SARS-CoV-2-neutralisierenden monoklonalen Antikörpers DZIF-10c an SARS-CoV-2-
infizierte und -uninfizierte Personen

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Trial to test the safety, half-life, and antiviral efficacy of a new drug (human antibody) called DZIF-10c (administered inhalatively) in healthy volunteers and SARS-CoV-2-infected participants

Studie zur Bewertung der Sicherheit, Halbwertszeit und antiviralen Wirksamkeit eines neuen Medikamentes (humaner Antikörper) namens DZIF-10c (inhalativ verabreicht) mit gesunden Personen und mit SARSCoV2 infizierten Personen

A.3.2

Name or abbreviated title of the trial where available

DZIF-10c_Inhalation

A.4.1

Sponsor's protocol code number

Uni-Koeln-4370

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04631705

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	University of Cologne
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Boehringer Ingelheim
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CTC Cologne
B.5.2	Functional name of contact point	Project Manager
B.5.3	Address:
B.5.3.1	Street Address	Gleueler Str. 269
B.5.3.2	Town/ city	Cologne
B.5.3.3	Post code	50935
B.5.3.4	Country	Germany
B.5.4	Telephone number	0049221478 88790
B.5.5	Fax number	0049221478 88209
B.5.6	E-mail	sebastian.meller@uk-koeln.de

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	DZIF-10c
D.3.2	Product code	EX 14870
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EX 14870
D.3.9.2	Current sponsor code	EX 14870
D.3.9.3	Other descriptive name	DZIF-10c
D.3.9.4	EV Substance Code	SUB218333
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	DZIF-10c
D.3.2	Product code	EX 14870
D.3.4	Pharmaceutical form	Concentrate for nebuliser solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EX 14870
D.3.9.2	Current sponsor code	EX 14870
D.3.9.3	Other descriptive name	DZIF-10c
D.3.9.4	EV Substance Code	SUB218333
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solvent for...
D.8.4	Route of administration of the placebo	Inhalation use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

SARS-CoV-2 infection (only mild to moderate disease)

SARS-CoV-2 Infektion mit leichten oder mildem Krankheitsbild

E.1.1.1

Medical condition in easily understood language

COVID-19 (only mild to moderate disease)

COVID-19 mit leichten oder mildem Krankheitsbild

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.0
E.1.2	Level	LLT
E.1.2	Classification code	10084272
E.1.2	Term	SARS-CoV-2 infection
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

- To evaluate the safety and tolerability of a single inhaled application of DZIF-10c in SARS-CoV-2-uninfected and SARS-CoV-2-infected individuals.
- To evaluate the safety and tolerability of a single combined inhaled and intravenous application of DZIF-10c in SARS-CoV-2-infected individuals.

E.2.2

Secondary objectives of the trial

All to be determined after a single inhaled application of DZIF-10c or a single combined inhaled and intravous application of DZIF-10c:

- To determine the systemic DZIF-10c exposure (AUC0-672h (i.e., from the day 0 to the day 28 visit)).
- To determine the development of antibodies targeting DZIF-10c (anti-drug antibodies, ADA)-
- To determine the effect of DZIF-10c on SARS-CoV-2 shedding in nasopharyngeal swabs by qRT-PCR

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Groups 1A-1C
- Age 18 to 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 to 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 angeusia, 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)

E.4

Principal exclusion criteria

- 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.
- Blood laboratory parameter abnormalities as listed below
- 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 unwilligness to comply with the requirements for highly effective contraception

E.5 End points

E.5.1

Primary end point(s)

- The rate of Adverse Events after DZIF-10c inhalation.
- The rate of Adverse Events after the combined inhalation and intranveous infusion of DZIF-10c.

E.5.1.1

Timepoint(s) of evaluation of this end point

- The dose limiting toxicity (DLT) period comprises the first 7 days after DZIF-10c inhalation, adverse events until end of follow up period
(90 day after treatment with DZIF-10c)
- The dose limiting toxicity (DLT) period comprises the first 7 days after the combined inhalation and intranveous infusion of DZIF-10c, adverse events until end of follow up period (90 day after treatment with DZIF-10c)

E.5.2

Secondary end point(s)

To be determined after a single inhaled application of DZIF-10c or a single combined inhaled and intravenous application of DZIF-10c:
- The Area under the Curve (AUC) for DZIF-10c levels from the day 0 to the day 28 visit (AUC0-672h)
- The frequency and magnitude of anti-drug antibodies targeting DZIF-10c.
- SARS-CoV-2 RNA shedding in nasopharyngeal swabs determined by qRT-PCR in SARS-CoV-2-infected individuals

E.5.2.1

Timepoint(s) of evaluation of this end point

please see protocol

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

Yes

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

1) open-label dose-escalation phase, 2 ) Randomized double-blind placebo-controlled phase

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-12-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-12-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-09-23

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