Clinical Trials Register

Summary
EudraCT Number:	2016-000936-17
Sponsor's Protocol Code Number:	GWEP1560
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2019-04-30
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

UK - MHRA

A.2

EudraCT number

2016-000936-17

A.3

Full title of the trial

A Randomized, Double-Blind, Placebo-Controlled Single-Ascending Dose Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of GWP42003-P in Conjunction with Hypothermia in Neonates with Moderate or Severe Hypoxic Ischemic Encephalopathy

A.3.1

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

A randomized trial to evaluate the safety, tolerability, and pharmacokinetics of GWP42003-P in conjunction with therapeutic hypothermia in neonates with moderate or severe birth asphyxia

A.4.1

Sponsor's protocol code number

GWEP1560

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	GW Research Ltd
B.1.3.4	Country	United Kingdom
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	GW Research Ltd
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GW Research Ltd
B.5.2	Functional name of contact point	GW Research Ltd Switchboard
B.5.3	Address:
B.5.3.1	Street Address	Sovereign House, Vision Park, Chivers Way
B.5.3.2	Town/ city	Histon, Cambridge
B.5.3.3	Post code	CB24 9BZ
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441223266800
B.5.5	Fax number	+441223235667
B.5.6	E-mail	info@gwpharm.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/3/15/1520
D.3 Description of the IMP
D.3.1	Product name	Cannabidiol (CBD)
D.3.2	Product code	GWP42003-P
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	Yes
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	Cannabidiol
D.3.9.1	CAS number	13956-29-1
D.3.9.2	Current sponsor code	GWP42003-P
D.3.9.3	Other descriptive name	CANNABIDIOL
D.3.9.4	EV Substance Code	SUB26600
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	3
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	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Neonatal Hypoxic-Ischemic Encephalopathy

E.1.1.1

Medical condition in easily understood language

Brain injury caused by a lack of oxygen-rich blood in a newborn's brain

E.1.1.2

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

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	10070512
E.1.2	Term	Hypoxic-ischemic encephalopathy
E.1.2	System Organ Class	100000004852

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10050081
E.1.2	Term	Neonatal hypoxia
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

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 assess the safety and tolerability of a single-ascending intravenous (IV) dose of GWP42003-P compared with placebo in neonates (minimum of 36 weeks plus 0 days gestational age) who are undergoing whole-body hypothermia (standard of care) for the treatment of NHIE

E.2.2

Secondary objectives of the trial

To determine the pharmacokinetics (PK) of cannabidiol (CBD) following a single IV dose of GWP42003-P
The exploratory objectives of this trial are
To assess the efficacy of a single IV dose of GWP42003-P compared with placebo in neonates who are undergoing whole-body hypothermia for the treatment of NHIE with respect to the following:
Degree of brain injury/recovery
Seizure burden
Neurodevelopmental impairment

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

6.2.1.1. Patient is male or female and ≥ 36 weeks of gestational age
6.2.1.2. Patient is receiving active or passive whole-body cooling/hypothermia since <6 hours from birth
6.2.1.3. Patient has perinatal depression based on at least 1 of the following:
• Apgar score ≤ 5 at 10 minutes, or;
• Need for resuscitation at 10 minutes (i.e., endotracheal or mask ventilation, or chest compressions), or;
• pH < 7.00 in umbilical cord, arterial, or capillary blood < 60 minutes of age, or;
• Base deficit ≥ 16 mmol/L in umbilical cord or any blood sample (arterial,
venous, or capillary) < 60 minutes of age.
6.2.1.4. Patient has moderate to severe encephalopathy consisting of altered state of consciousness (lethargy, stupor, or coma) AND at least 1 of the following:
• Hypotonia
• Abnormal reflexes, including oculomotor or pupillary abnormalities
• An absent or weak suck
• Clinical seizures
6.2.1.5. Patient has ≥ 30 minutes’ duration of abnormal background activity on cEEG prior to IMP administration, based on the presence of 1 of the following:
• Suppressed activity
• Moderately abnormal activity
• Seizures of 30 seconds’ duration or more
6.2.1.6. Patient’s parent(s)/legal representative (if appropriate according to local laws) is/are willing and able to give informed consent for participation in the trial
6.2.1.7. Patient’s parent(s)/legal representative (if appropriate according to local laws) is/are willing and able (in the PI’s opinion) to comply with all trial
requirements
6.2.1.8. Patient’s parent(s)/legal representative is/are willing to allow the responsible authorities to be notified of participation in the trial, if mandated by local law
6.2.1.9. Patient’s parent(s)/legal representative (if appropriate according to local laws) is/are willing to allow his or her primary care practitioner (if they have one)
and consultant (if they have one) to be notified of participation in the trial if the primary care practitioner/consultant is different from the PI

E.4

Principal exclusion criteria

6.2.2.1. Patient’s mother used recreational or medicinal cannabis or synthetic cannabinoid-based medications (including Sativex®) within 4 weeks of birth
of the patient
6.2.2.2. IMP cannot be administered within 12 hours of birth and after whole-body hypothermia has been initiated
6.2.2.3. Patient’s birth weight < 1800 g (e.g., intrauterine growth restriction)
6.2.2.4. Patient has severely abnormal background activity on continuous electroencephalography (cEEG) classified by continuous electrographic
seizures suggestive of status epilepticus
6.2.2.5. Patient has potential hypersensitivity to cannabinoids or any of the excipients of the IMPs based on family history
6.2.2.6. Patient has a living twin (or higher order multiple) who is also being cooled
6.2.2.7. Patient’s head circumference is < 30 cm
6.2.2.8. Redirection of the patient’s care is being considered due to moribund condition
6.2.2.9. Patient’s parents have diminished capacity and autonomy
6.2.2.10. Patient has a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN)
6.2.2.11. Patient has a genetic or congenital condition that affects neurodevelopment or requires multiple surgeries (e.g., congenital viral infection, hydrops, complex congenital heart disease, severe dysmorphic features, etc.)
6.2.2.12. Patient has any other significant disease or disorder that, in the opinion of the PI, may put the patient at risk because of participation in the trial, may
influence the result of the trial, or may affect the patient’s ability to take part in the trial
6.2.2.13. Any abnormalities identified following a physical examination of the patient that, in the opinion of the PI, would jeopardize the safety of the patient or
interfere with trial conduct if they took part in the trial
6.2.2.14. Patient is participating in another interventional trial (note: this does not include observational studies)

E.5 End points

E.5.1

Primary end point(s)

The safety and tolerability profile of a single IV dose of GWP42003-P, compared with placebo, will be assessed through monitoring of the following:
• Frequency, type, and severity of adverse events (AEs) up to 30 days of life
• Mortality rate up to 30 days of life
• Clinically significant changes in the following up to discharge from the neonatal intensive care unit (NICU):
o Laboratory parameters
o Cardiorespiratory monitoring
o Vital signs

E.5.1.1

Timepoint(s) of evaluation of this end point

Physical and Neurological Exam: Visits 1, 2, 3, 4, 5 and 7.
Vital Signs: Hourly from birth to 24 hours postnatal and every 4 hours until 120 hours postnatal
Respiratory Support: Every 8 hours from birth until 120 hours postnatal.
Safety Laboratory Sampling: Prior to IMP administration, at 36 hours (± 12 hours) of life and 72 hours (± 12 hours) of life.
Clinical Laboratory Sampling: Per routine care throughout hospitalization.

E.5.2

Secondary end point(s)

The plasma PK of CBD will be investigated. Plasma PK parameters will be determined using a population-based approach with sparse sampling.

E.5.2.1

Timepoint(s) of evaluation of this end point

PK Samples completed 2 minutes prior to completion of the infusion and at 1, 2, 4 and 8 hours after the end of infusion.

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

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Safety, Tolerability and Pharmacokinetics

E.7.2

Therapeutic exploratory (Phase II)

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

Yes

E.8.1.5

Parallel group

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

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

Yes

E.8.4

The trial involves multiple sites in the 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

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

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

Yes

F.1.1.2.1

Number of subjects for this age range:

F.1.1.3

Newborns (0-27 days)

Yes

F.1.1.3.1

Number of subjects for this age range:

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.1.3

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

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

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

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Paediatric (Newborn) Population

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

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)

This is a single dose IMP administration, no further treatment will be given. Routine standard of care will be continued after the subject has ended participation in the trial.

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

2019-06-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-07-23

P. End of Trial
P.	End of Trial Status	GB - no longer in EU/EEA

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IMP with orphan designation in the indication
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