Clinical Trials Register

Summary
EudraCT Number:	2019-004523-21
Sponsor's Protocol Code Number:	V1605-201
National Competent Authority:	Lithuania - SMCA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-07-09
Trial 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

Lithuania - SMCA

A.2

EudraCT number

2019-004523-21

A.3

Full title of the trial

A Phase 2 Study to Evaluate the Sensitivity and Specificity of DBV1605, a Ready to Use Atopy Patch Test for the Diagnosis of Non-Immunoglobulin E Mediated Cow’s Milk Allergy in Children.

A.3.1

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

A clinical study to assess DBV1605 for the diagnosis of cow's milk allergy in children.

A.3.2

Name or abbreviated title of the trial where available

APTITUDE

A.4.1

Sponsor's protocol code number

V1605-201

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	DBV Technologies S.A.
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	DBV Technologies SA
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	DBV Technologies S.A.
B.5.2	Functional name of contact point	DBV Technologies S.A.
B.5.3	Address:
B.5.3.1	Street Address	177-181 avenue Pierre Brossolette
B.5.3.2	Town/ city	Montrouge
B.5.3.3	Post code	92120
B.5.3.4	Country	France
B.5.6	E-mail	aptitude.study@dbv-technologies.com

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.3.2	Product code	DBV1605 active and control patch
D.3.4	Pharmaceutical form	Cutaneous patch
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Cutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Milk allergen extract
D.3.9.3	Other descriptive name	COW MILK EXTRACT
D.3.9.4	EV Substance Code	SUB84552
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	144 to 216
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	Yes
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	Yes
D.3.11.9	Recombinant medicinal product	No
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Non-Immunoglobulin E Mediated Cow’s Milk Allergy

E.1.1.1

Medical condition in easily understood language

Cow’s Milk Allergy

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10011240
E.1.2	Term	Cow's milk allergy
E.1.2	System Organ Class	100000004870

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 assess the diagnostic performance of DBV1605 for the diagnosis of non-Immunoglobulin E (IgE) mediated cow’s milk allergy (CMA) in children with symptoms suggestive of non-IgE mediated CMA based on the sensitivity and the
specificity.

E.2.2

Secondary objectives of the trial

The secondary objectives of the study are to:
• Estimate the specificity of DBV1605 in a control group of subjects;
• Assess the diagnostic performance of DBV1605 in different subgroups of interest;
• Assess the adhesion and application duration of the DBV1605 patch;
• Assess the safety of a single 48-hour application of DBV1605.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

DISEASE GROUP
• Male or female subjects aged >6 months to ≤24 months at Screening Visit. Age from >28 days to ≤24 months at Screening Visit after Safety Review Committee (SRC) recommendations are given.
• Subjects with a history of symptoms that are consistent with non-IgE mediated CMA as per Investigator's assessment, by either:
o Two or more gastrointestinal symptoms (vomiting, diarrhea, persistent distress/colic, regurgitation, constipation), that lasted at least 1 week within 1 month prior to Screening Visit
o Blood in stool,
• Subjects with any type of diet containing dairy products with cow's milk protein (e.g. cow's milk consumption, cow's milk partial elimination, partially hydrolyzed milk) prior Screening Visit or who have started a cow's milk elimination diet not more than 4 weeks prior to Screening Visit.
• Subjects with a negative cow's milk SPT: mean wheal diameter <3 mm and negative control <1 mm.

CONTROL GROUP
Subjects may be included in the control group only if they meet, among other criteria, the following inclusion criteria:
• Male or female subjects aged >28 days to ≤24 months at Screening/Visit 1,
• Subjects having no medical history of any type of allergy, including no history of IgE-mediated allergic reactions to cow's milk and with no medical history of any food allergy in their family (parents, sibling),
• Subjects who tolerate at least 200 mL of cow's milk or equivalent dairy foods daily within 4 weeks prior to Screening/Visit 1.
• Subjects with negative cow's milk SPT: mean wheal diameter <3 mm and negative control <1 mm.

E.4

Principal exclusion criteria

criteria is within the study protocol)
DISEASE GROUP
1 Subjects with an established diagnosis of non-IgE mediated CMA made by a physician upon cow's milk protein challenge.
2 Breast-fed subjects at Screening Visit.
3 Subjects on a cow's milk protein-free diet including an AA-based formula or an extensively hydrolyzed formula initiated more than 4
weeks prior to Screening Visit.
4 Subjects with a history of confirmed FPIES or Heiner's syndrome.
5 Any contraindication to a cow's milk challenge, in particular subjects with a history of severe anaphylactic reaction to cow's milk. Severe
anaphylaxis is defined as Grade 3 of the Anaphylaxis Staging System, including:
• Severe hypoxia, persistent hypotension or more than 20% drop in blood pressure, neurological compromise, or
• Cyanosis or SpO2 ≤ 92% at any stage, confusion, cardiovascular collapse, loss of consciousness, bradycardia, cardiac arrest.
6 Subjects with a convincing history of IgE-mediated CMA.
8 Subjects with diagnosis of asthma or recurrent wheezing that fulfills any of the following criteria:
- Uncontrolled asthma or recurrent wheezing (as per Global Initiative for Asthma (GINA) guidelines).
- Asthma or recurrent wheezing that is considered uncontrolled per GINA guidelines or has had modifications in their asthma or wheezing
controller medication within 3 months prior Screening Visit.
10 Known hypersensitivity to any of the DBV1605 components (except to milk proteins).
11 Known hypersensitivity to any component of the food challenge formula (except to milk proteins).
12 A history of any immunotherapy for CMA.
15 Any disorder in which epinephrine is contraindicated such as congenital cardiac malformation, uncontrolled hypertension, or serious
ventricular arrhythmias.
17 Treatment with antihistamines within 1 to 7 days (depending on halflife and specified in APPENDIX 3) prior to Screening Visit or inability to
discontinue antihistamines for the minimum wash-out periods required prior to SPT or food challenges.
18 Treatment with topical steroid applied on the back within 30 days prior to Screening Visit.

E.5 End points

E.5.1

Primary end point(s)

The sensitivity and the specificity of DBV1605 based on skin reactivity readings after 48 hours and 72 hours will be compared to the results of the DBPCFC in subjects of the disease group.

E.5.1.1

Timepoint(s) of evaluation of this end point

The DBV1605 patch test will be considered positive if, after 48 hours and/or 72 hours following application:
• The skin reactivity under the control patch is rated Grades 0 or 1, and
• The skin reactivity under the active patch is rated at least 1 grade higher than the control patch.
The DBV1605 patch test will be considered negative if after both 48 hours and 72 hours:
• The skin reactivity under the control patch is rated Grades 0 or 1, and
• The skin reactivity under the active patch is rated the same grade as the control patch or 1 grade lower than the control patch.

E.5.2

Secondary end point(s)

In the disease group of subjects:
• DBV1605 sensitivity and specificity after readings at 48 hours;
• DBV1605 sensitivity and specificity after readings at 72 hours;
• DBV1605 sensitivity and specificity considering the test positive if, after 48 hours and/or 72 hours following application:
o The skin reactivity under the control patch is rated Grades 0 or 1, and
o The skin reactivity under the active patch is rated at least 2 grades higher than the control patch.
In addition, other indicators of DBV1605 diagnostic performance could be explored, and subgroups could be considered for the analysis. The following secondary analyses will be conducted in the control group to confirm the results observed in the disease group:
• DBV1605 specificity after readings at 48 hours and 72 hours in the control group.
The adhesion of DBV1605 will be assessed with:
• The proportions of patches with adhesion scored Grade 0 or 1 and the proportions of patches with adhesion scored higher than 1 at application;
• The proportions of patches with adhesion scored Grade 0 or 1 and the proportions of patches with adhesion scored higher than 1 at removal.
The duration of DBV1605 application will be assessed with:
• The proportions of patches without detachment of the occlusive chamber as assessed by the parents/guardians at different timepoints: 24 hours ±1 hour, 36 hours ±1 hour and 48 hours ±1 hour;
• The proportions of patches present at the application site more than 36 hours after application, excluding voluntary removal;
• The mean duration of patch application until removal or detachment.

E.5.2.1

Timepoint(s) of evaluation of this end point

DBV1605 sensitivity and specificity readings at after 48 hours and 72 hours. The test will be considered positive if, after 48 hours and/or
72 hours following application:
o The skin reactivity under the control patch is rated Grades 0 or 1, and
o The skin reactivity under the active patch is rated at least 2 grades higher than the control patch.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

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)

E.7.1.1

First administration to humans

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

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

active and control patch of the same IMP

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

United States

Italy

Lithuania

E.8.7

Trial has a data monitoring committee

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

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

230

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

180

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

230

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)

Subjects will receive medical standard of care according to the judgment of the treating physician.

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

2020-09-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-08-27

P. End of Trial
P.	End of Trial Status	Completed

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