Clinical Trials Register

Summary
EudraCT Number:	2019-001605-24
Sponsor's Protocol Code Number:	GWND19002
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:	2019-10-23
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

2019-001605-24

A.3

Full title of the trial

An open-label extension trial to investigate the long-term safety of cannabidiol oral solution (GWP42003-P, CBD-OS) in patients with Rett Syndrome

A.3.1

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

An open label extension study for long-term safety of GWP42003-P in patients with Rett Syndrome

A.4.1

Sponsor's protocol code number

GWND19002

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/095/2020

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	Yes
D.2.1.1.1	Trade name	CBD Oral solution, is known as Epidyolex and is the approved name in the EU
D.2.1.1.2	Name of the Marketing Authorisation holder	GW Pharma B.V (International)
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Cannabidiol (CBD)
D.3.2	Product code	GWP42003-P
D.3.4	Pharmaceutical form	Oral solution
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	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	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	Yes
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

Rett syndrome (RTT) [typical or atypical]

E.1.1.1

Medical condition in easily understood language

Rett syndrome (RTT) [typical or atypical]

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

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	10077709
E.1.2	Term	Rett syndrome
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic 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 evaluate the long-term safety of GWP42003-P in patients with RTT

E.2.2

Secondary objectives of the trial

•To evaluate the effect of GWP42003-P in measures of disease severity
o Rett Syndrome Behaviour Questionnaire (RSBQ)
o Clinical Global Impressions - Improvement (CGI-I)
o Clinical Global Impressions - Severity (CGI-S)
o 9-items Motor Behavioral Assessment (MBA-9)
o Children’s Sleep Habits Questionnaire (CSHQ)

Exploratory objectives:
•To evaluate the effect of GWP42003-P on caregiver and patient quality of life (QoL)
o 36-item Short Form [SF-36] and Child Health Questionnaire Parent Form 50 [CHQ-PF50], respectively
• To evaluate the effect of GWP42003-P on health utilization
o Hospital Services Use Questionnaire
o Caregiver Assessment of Rett Symptoms

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

For inclusion in the trial, patients must fulfil all of the following criteria:
• Patient has completed all scheduled visits of the treatment phase of the RCT, GWND18064, and has transitioned to OLE by the point of RCT follow-up (Visit 11).
• Patient (if possessing adequate understanding, in the investigator’s opinion) and/or the patient’s parent(s)/legal representative is willing and able to give informed consent/assent for participation in the trial.
• Patient and the patient’s caregiver are willing and able (in the investigator’s opinion) to comply with all trial requirements (including the completion of all caregiver assessments by the same caregiver throughout the trial).
• Patient must have the ability to swallow the investigational medicinal product (IMP) provided as a liquid solution or the ability for the IMP to be delivered via gastrostomy (G) or nasogastric (NG) feeding tube (only G- or NG-tubes made from polyurethane or silicon are allowed).
• Patient and/or parent(s)/legal representative is willing to allow the responsible authorities to be notified of participation in the trial, if mandated by local law.
• Patient and/or parent(s)/legal representative is willing to allow the patient’s primary care practitioner (if the patient has one) and consultant (if the patient has one) to be notified of participation in the trial if the primary care practitioner/consultant is different from the investigator.

Per Protocol Annex 1, with the exception of the inclusion criterion that requires patients must have completed all scheduled visits of the treatment phase of the RCT, GWND18064, and transitioned to OLE by the point of RCT follow-up (Visit 11), all inclusion and exclusion criteria defined in the GWND19002 protocol must be met. In addition, the following inclusion criteria apply:
Inclusion criteria
• Patient has completed all scheduled visits of the treatment phase of the RCT, either in clinic or completed as many scheduled assessments as feasible remotely, or has withdrawn from GWND18064 after discussion with the medical monitor due to inability to adequately monitor safety and benefit risk.
• Visit 1 is taking place no later than 3 months after screening of new subjects for study GWND18064 has reopened at their trial site.

E.4

Principal exclusion criteria

The patient may not enter the trial if ANY of the following apply:
• Patient meets the withdrawal criteria (including clinically significant abnormal laboratory values), in the investigator’s opinion.
• Patient met during the RCT the criteria for permanent IMP discontinuation (unless in case of an AE, if AE was not considered related with the IMP; patients that met alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevations discontinuation criteria must be excluded).
• Females of childbearing potential, unless willing to ensure that they or their partner use a highly effective method of birth control (e.g., combined [estrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation [oral, intravaginal or transdermal], progestogen-only hormonal contraception associated with inhibition of ovulation [oral, injectable or implantable ] intrauterine devices/hormone-releasing systems , bilateral tubal occlusion, vasectomized partner, sexual abstinence during the trial and for 3 months after the last dose.
• Patient has been previously enrolled and dosed in this trial.
• Patient is unwilling to abstain from donation of blood during the trial.
• Male participants who are fertile (i.e., after puberty unless permanently sterile by bilateral orchidectomy) and with a partner of childbearing potential unless agree to ensure that they use male contraception (e.g., condom) or remain sexually abstinent during the trial and for 3 months after the last dose.

Per Protocol Annex 1, with the exception of the inclusion criterion that requires patients must have completed all scheduled visits of the treatment phase of the RCT, GWND18064, and transitioned to OLE by the point of RCT follow-up (Visit 11), all inclusion and exclusion criteria defined in the GWND19002 protocol must be met. In addition, the following exclusion criteria apply:
• Any history of suicidal behavior or any suicidal ideation in the last month or at Visit 1.
• Patient has clinically relevant abnormalities in the electrocardiogram measured at Visit 1 (including QT interval, corrected by Bazett's correction formula [QTcB] > 450 msec, average of 3 measurements).
• Patient has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP (active and placebo), such as sesame oil.
• Patient has moderately impaired hepatic function at screening, defined as serum ALT or AST > 3 × ULN or total bilirubin [TBL] > 2 × ULN.
This criterion can only be confirmed once the Visit 1 laboratory results are available. If Visit 1 laboratory results indicate the patient is not eligible, the patient must be withdrawn. Prior to withdrawal for the transaminase elevations noted above, the investigator may choose to confirm the transaminase elevations by repeating the following laboratory tests within 24 to 48 hours: ALT, AST, TBL, international normalized ratio, % eosinophils, gamma-glutamyl transferase, alkaline phosphatase, and eosinophils. Should the above transaminase elevation criteria be confirmed, the patient must be withdrawn from the trial.
• Patient has received an IMP (other than GWND18064 IMP) since participation in GWND18064.
• Patient has been taking felbamate for less than 1 year prior to Visit 1
• Patient is currently using or has used recreational or medicinal cannabis, cannabinoid-based medications (including Sativex
® [nabiximols]) or cannabidiol oral solutions (excluding GWND18064 IMP) within the 3 months prior to Visit 1 and is unwilling to abstain for the duration of the trial.
• Patient has any other systemic dysfunction (e.g., gastrointestinal, renal, respiratory) or significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the trial, may influence the result of the trial, or the patient’s ability to participate in the trial.
• Any abnormalities identified following a physical examination of the patient that, in the opinion of the investigator, would jeopardize the safety of the patient if the patient took part in the trial.
• Female patient is pregnant (positive pregnancy test) or lactating.

E.5 End points

E.5.1

Primary end point(s)

Safety:
The long-term safety profile of GWP42003-P will be assessed by evaluating changes in the following, relative to the prerandomization baseline of the RCT:
• AEs
• Clinical laboratory parameters
• Vital signs
• Physical examination procedures
• 12-lead ECG
• Effects on menstruation cycles
• Suicidality
• Change in growth and development by measurement of height, weight, IGF-1 levels, and Tanner Staging (for patients aged ≥ 7 years or earlier, if clinically indicated by the onset of menarche or other signs of precocious puberty)

E.5.1.1

Timepoint(s) of evaluation of this end point

Please refer to the schedule of the assessment within the protocol (Appendix 1).

E.5.2

Secondary end point(s)

The following will be assessed by evaluating changes relative to the prerandomization baseline of the RCT:
• RSBQ
• CGI-I
• CGI-S
• MBA-9
• CSHQ

E.5.2.1

Timepoint(s) of evaluation of this end point

Please refer to Protocol schedule of events table for detailed information

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

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

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)

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

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

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

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

Canada

France

Italy

Spain

United Kingdom

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

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

Yes

F.1.1

Number of subjects for this age range:

252

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

135

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

105

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)

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Rett Syndrome

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

252

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 continue on standard of care after the study end.

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

2019-11-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-01-15

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

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