Clinical Trials Register

Summary
EudraCT Number:	2015-005033-53
Sponsor's Protocol Code Number:	EG-01-1962-03
National Competent Authority:	Finland - Fimea
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2016-09-15
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

Finland - Fimea

A.2

EudraCT number

2015-005033-53

A.3

Full title of the trial

Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled,
Parallel-Group, Efficacy and Safety Study Comparing EG-1962 to Standard
of Care Oral Nimodipine in Adults with Aneurysmal Subarachnoid
Hemorrhage

Faasi 3, monikeskustutkimus, randomoitu, kaksoissokkoutettu, plasebokontorolloitu,
rinnakkais-ryhmä, EG-1962:n tehokkuus ja turvallisuus
verrattuna normaaliin hoitokäytäntöön, joka on suun kautta annettava
Nimodipiini aikuisilla, joilla on todettu aneyrysman puhkeamisesta johtuva
lukinkalvon alainen verenvuoto

A.3.1

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

An international clinical study to compare a new investigational (not yet
approved) treatment called EG-1962 to compare against the current
standard of care, oral Nimodipine, for the improvement of symptoms you
may experience after a brain hemorrhage.

A.3.2

Name or abbreviated title of the trial where available

NEWTON 2

A.4.1

Sponsor's protocol code number

EG-01-1962-03

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02790632

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	Edge Therapeutics, 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	Edge Therapeutics, 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	Edge Therapeutics, Inc.
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	300 Connell Drive, Suite 4000
B.5.3.2	Town/ city	Berkeley Heights, NJ
B.5.3.3	Post code	07922
B.5.3.4	Country	United States
B.5.4	Telephone number	19083445257
B.5.5	Fax number	19087901212
B.5.6	E-mail	regdocs@edgetherapeutics.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	Yes
D.2.5.1	Orphan drug designation number	EU/3/15/1554- EMA/OD/088/15
D.3 Description of the IMP
D.3.1	Product name	EG-1962
D.3.2	Product code	EG-1962
D.3.4	Pharmaceutical form	Powder and solvent for prolonged-release suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intraventricular use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NIMODIPINE
D.3.9.1	CAS number	66085-59-4
D.3.9.2	Current sponsor code	: 3-(2-methoxyethyl) 5-propan-2-yl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxyl
D.3.9.3	Other descriptive name	nimodipine encapsulated within a bioresorbable poly-D, L-lactide-co-glycolide (PLGA) matrix and suspended with a sodium hyaluronate based buffer making a suspension that releases nimodipine over an extended period.
D.3.9.4	EV Substance Code	SUB09297MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	600
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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	Nimotop
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer PLC
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	nimodipino, nimodipinum, nimodipine
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NIMODIPINE
D.3.9.1	CAS number	66085-59-4
D.3.9.3	Other descriptive name	3-(2-methoxyethyl) 5-propan-2-yl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
D.3.9.4	EV Substance Code	SUB09297MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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	Intraventricular use (Noncurrent)
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Aneurysmal subarachnoid hemorrhage (aSAH)

E.1.1.1

Medical condition in easily understood language

Subarachnoid hemorrhage is bleeding in the space between your brain
and surrounding membrane. Bleeding results from the rupture of an
abnormal bulge in a blood vessel in your brain (brain aneurysm).

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the efficacy of intraventricular EG-1962 to standard of care
oral nimodipine in subjects with aSAH

E.2.2

Secondary objectives of the trial

To determine the safety of intraventricular EG-1962 compared to
standard of care oral nimodipine in subjects with aSAH

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female between the ages of 18 to 75 years, inclusive
2. Ruptured saccular aneurysm confirmed by angiography (CTA, MRA or
catheter) and repaired
by neurosurgical clipping or endovascular coiling
3. Subarachnoid hemorrhage on CT scan (pre-repair) of grade 2-4 on the
modified Fisher scale
(diffuse [clot present in both hemispheres] thick or thin, or local thick)
4. External ventricular drain in place
5. WFNS grade 2, 3, or 4 assessed during the Pre-randomization Phase
after repair of the
aneurysm but prior to randomization
6. The subject must be able to receive intraventricular IP within 48
hours after the onset of aSAH and within 4 hours after the start time of
intraventricular IP suspension in the pharmacy. Onset of aSAH is defined
as the time the subject experiences the first symptom of aSAH (e.g.,
severe headache or loss of consciousness reported either by the subject
or by a witness). If found unconscious, the onset of SAH is defined as
the time the subject was last known normal
7. Female subjects of child-bearing potential must have a negative
pregnancy test (urine or serum) during the Pre-randomization Phase and
must agree to use adequate birth control for at least 30 days following
the end of the Treatment Period. Male subjects must agree to use
adequate birth for at least 30 days after the end of the Treatment Period
8. Signed informed consent from the subject or the subject's legal
representative after the
completion of aneurysm repair but prior to any study-specific procedures
being performed
9. Able and willing to comply with follow up visit schedule

E.4

Principal exclusion criteria

1. Major complication during aneurysm repair such as, but not limited to,
massive intraoperative hemorrhage, brain swelling, arterial occlusion, or
inability to secure the ruptured aneurysm
2. Angiographic vasospasm prior to randomization
3. Clinical or radiological evidence of a cerebral infarction with
neurological deficit
4. Increased intracranial (ICP) pressure >30 mm Hg lasting >4 hours
anytime during the Prerandomization Phase
5. Substantial intraventricular hemorrhage
6. Aneurysm repair requiring flow diverting stent or stent-assisted
coiling and dual antiplatelet
therapy
7. Subject is expected to undergo repair of additional aneurysms within
90 days in cases where
multiple aneurysms were identified during the Pre-randomization
PhaseHemodynamically unstable during the Pre-randomization Phase
(i.e., systolic blood pressure (SBP) <100 mm Hg, requiring >6 L colloid,
or crystalloid fluid resuscitation)
9. Cardiopulmonary resuscitation was required during the Prerandomization
Phase
10. Symptoms or electrocardiogram (ECG) signs of acute myocardial
infarction or unstable angina pectoris prior to randomization
11. Electrocardiogram evidence and/or physical findings compatible with
second or third degree heart block or of cardiac arrhythmia associated
with hemodynamic instability
12. Echocardiogram, if performed as part of standard of care before
randomization, revealing a left ventricular ejection fraction <40%
13. Severe or unstable concomitant condition or disease (e.g., known
significant neurologic deficit, cancer, hematologic or coronary disease),
or chronic condition (e.g., liver disease, kidney disease or psychiatric
disorder), that, in the opinion of the investigator, may increase the risk
associated with study participation or IP administration, or may
interfere with the interpretation of study results
14. Subjects who have received an investigational product or
participated in another interventional clinical study within 30 days prior
to randomization. Subjects participating in a
non-interventional study that has no bearing on assessment of EG-1962
or enteral nimodipine
may be enrolled per guidelines of the local Institutional Review Board
(IRB)/Independent
Ethics Committee (IEC)
15. Known hypersensitivity to nimodipine or other dihydropyridine
calcium channel antagonists, poly-D, L-lactide-co-glycolide (PLGA), or
hyaluronic acid

E.5 End points

E.5.1

Primary end point(s)

Proportion of subjects with a favorable outcome measured on the
Extended Glasgow Outcome Scale (GOSE) at Day 90 by a blinded
assessor

E.5.1.1

Timepoint(s) of evaluation of this end point

90 Days

E.5.2

Secondary end point(s)

Proportion of subjects with favorable neurocognitive outcome at Day 90
measured by the Montreal Cognitive Assessment (MoCA) by a blinded
assessor

E.5.2.1

Timepoint(s) of evaluation of this end point

90 Days

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

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

Information not present in EudraCT

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

Information not present in EudraCT

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

Information not present in EudraCT

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

Australia

Austria

Canada

Czech Republic

Denmark

Finland

Germany

Hong Kong

Israel

New Zealand

Singapore

United States

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

LVSV

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

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)

F.1.2.1

Number of subjects for this age range:

262

F.1.3

Elderly (>=65 years)

F.1.3.1

Number of subjects for this age range:

112

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

In case the subject is not capable to give consent personally, the
signed informed consent will be obtained from the subject's legal
representative
after the completion of aneurysm repair but prior to any study-specific
procedures being performed

F.3.3.7

Others

Information not present in EudraCT

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

180

F.4.2.2

In the whole clinical trial

374

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

2016-12-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-11-18

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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