Clinical Trials Register

Summary
EudraCT Number:	2014-001063-12
Sponsor's Protocol Code Number:	EVB-003
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-03-20
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Sweden - MPA

A.2

EudraCT number

2014-001063-12

A.3

Full title of the trial

A phase III, multi-center, randomized, double blind, active and placebo control, single dose trial to demonstrate the efficacy and safety of DWP-450 in adult subjects for treatment of moderate-to-severe glabellar lines

A.3.1

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

A clinical trial demonstrating the safety and efficacy of treatment of lines between the eye brows with the test drug DWP-450 in adults by comparison with Botox and Placebo.

A.3.2

Name or abbreviated title of the trial where available

EV003

A.4.1

Sponsor's protocol code number

EVB-003

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	Evolus Inc.
B.1.3.4	Country	United States
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	Evolus Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Evolus Inc.
B.5.2	Functional name of contact point	Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	1027 Garden Street
B.5.3.2	Town/ city	Santa Barbara
B.5.3.3	Post code	CA 93101
B.5.3.4	Country	United States
B.5.4	Telephone number	+18056174589
B.5.5	Fax number	+18054563031

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	Yes
D.2.1.1.1	Trade name	Nabota
D.2.1.1.2	Name of the Marketing Authorisation holder	Daewoong Pharmaceutical Co., Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	Korea, Republic of
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	DWP-450
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BOTULINUM TOXIN TYPE A
D.3.9.1	CAS number	93384-43-1
D.3.9.2	Current sponsor code	DWP-450
D.3.9.3	Other descriptive name	BoNT/A
D.3.9.4	EV Substance Code	SUB13117MIG
D.3.10	Strength
D.3.10.1	Concentration unit	U unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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)	No
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Botox, 100 Allergan Units
D.2.1.1.2	Name of the Marketing Authorisation holder	Allergan Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Botox
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BOTULINUM TOXIN TYPE A
D.3.9.1	CAS number	93384-43-1
D.3.9.4	EV Substance Code	SUB13117MIG
D.3.10	Strength
D.3.10.1	Concentration unit	U unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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)	No
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
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 injection
D.8.4	Route of administration of the placebo	Intramuscular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

moderate-to-severe glabellar lines

E.1.1.1

Medical condition in easily understood language

lines between the eyebrows and above the nose

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10052609
E.1.2	Term	Glabellar frown lines
E.1.2	System Organ Class	100000004858

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 demonstrate the safety and efficacy of DWP-450 purified botulinum neurotoxin, Type A in treatment of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adult subjects at maximum frown.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Subject is an adult, of at least 18 years of age
-Subject understands and signs the informed consent and can comply with study instructions
-Subject has moderate to severe glabellar lines at maximum frown as assessed by the investigator using the GLS (GLS=2 or 3)
-Subject is willing and able to complete the entire course of the study
-Subject finds their glabellar lines have an important psychological impact (on mood, anxiety and/or depressive symptoms)

E.4

Principal exclusion criteria

A subject must not meet the following key exclusion criteria in order to be eligible for enrollment in the study:
-Previous treatment with botulinum toxin of any serotype in the forehead area within the last 6 months
-Previous treatment with any facial aesthetic procedure (e.g., injection with fillers, chemical peeling, photo rejuvenation) in the glabellar area within the last 12 months
-Previous insertion of permanent material in the glabellar area
-Planned treatment with botulinum toxin of any serotype in any other body region during the study period
-Any surgery in the glabellar area including surgical removal of the corrugator, procerus, or depressor supercilii muscles or a combination of these, or scars in the glabellar area and the surrounding areas (including eye brow)
-Energy based or cryo-therapy based treatment of facial muscles superior to the lateral canthus
-Any other planned facial aesthetic procedure during the trial period, superior to the level of the lateral canthus (can continue with their usual skin care routine)
-Subjects not reasonably expected to respond to 20 units of botulinum toxin (e.g., inability to substantially lessen glabellar frown lines even by physically spreading them apart)
-Marked facial asymmetry
-Ptosis of eyelid and/or eyebrow, or history of eyelid and/or eyebrow ptosis
-History of facial nerve palsy
-Excessive dermatochalasis, deep dermal scarring, thick sebaceous skin
-Any active infection or history of herpes simplex or herpes zoster in the area of the injection sites
-Medical condition that may affect neuromuscular function (e.g., myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis)
-History of dysphagia or aspiration
-Subjects with prolonged bleeding times. If on a drug or supplement that prolongs bleeding times (eg non-steroidal, anti-inflammatory, anticoagulant, fish oil), wait 10 days or until bleeding times return to normal before injecting
-Evidence of recent alcohol or drug abuse
-Medical or psychiatric conditions that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study
-Breast feeding, pregnant or sexually active female subjects who are of childbearing potential and who are not willing to use an acceptable form of contraception
-Individuals who may be unduly influenced or fear a retaliatory response by hierarchy at the study center during the study
-Known allergy or hypersensitivity to botulinum toxin preparation
-Participation in another interventional clinical study within the last 30 days

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy measure will be based on the investigators assessment of the subject using the four-point Glabellar Line Scale (0=none, 1=mild, 2=moderate, 3=severe) at maximum frown. The primary endpoint for assessing the efficacy of DWP-450 is the proportion of subjects with a GLS score of 0 or 1 on Day 30 (±3 days), post injection of a study drug.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 30 (±3 days)

E.5.2

Secondary end point(s)

1) Proportion of subjects with at least a 1 point improvement in the GLS from Day 0 to Day 2 at maximum frown by Investigator assessment
2) Proportion of subjects with a GLS score of 0 or 1 on Day 30, at maximum frown by subject assessment
3) Proportion of subjects with at least a 1 point improvement in Subject Satisfaction from Day 0 to Day 30 (±3 days)
4) Difference between the mean HAD Scale scores from Day 0 to Day 90
5) Proportion of subjects with at least a 1 point improvement in the GLS from Day 0 to Day 150 at maximum frown by Investigator assessment

E.5.2.1

Timepoint(s) of evaluation of this end point

1) Day 0-2
2) Day 30
3) Day 30 (±3 days)
4) Day 90
5) Day 150

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

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)

Yes

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

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

France

Germany

Sweden

United Kingdom

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

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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:

435

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

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

400

F.4.2.2

In the whole clinical trial

497

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)

Once study is completed, all subjects will be offered an injection of an approved neuromodulator. The subject will be eligible if he or she desires it and if the Investigator agrees it is appropriate.
Subjects with any drug related AE should be followed until the Investigator and Sponsor consider the drug-related adverse event to have resolved, stabilized and no longer requires follow-up. Results of any follow-up will be provided to the Sponsor.

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

2015-04-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-04-22

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-04-27

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials