Clinical Trials Register

Summary
EudraCT Number:	2019-003369-16
Sponsor's Protocol Code Number:	GWAP19030
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-03-30
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2019-003369-16

A.3

Full title of the trial

A Randomized, Double-blind, Parallel-group Trial to Investigate the Safety and Efficacy of GWP42003-P Versus Placebo as Adjunctive Therapy in Participants with Schizophrenia Experiencing Inadequate Response to Ongoing Antipsychotic Treatment

A.3.1

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

An irregular trial in which the identity of those receiving the intervention in twin groups is concealed from both the administrators and subject until the test is completed. The trial is to check the safety and efficiency of GWP42003-P versus Placebo as a joining therapy in Participants with Schizophrenia Experiencing Inadequate Response to Ongoing Antipsychotic Treatment.

A.3.2

Name or abbreviated title of the trial where available

ALIGHT

A.4.1

Sponsor's protocol code number

GWAP19030

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04421456

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	00441223266800
B.5.5	Fax number	00441223235667
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 (International) B.V
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Oral solution
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

Schizophrenia is neurodevelopmental syndrome, results from gradual alterations in brain connectivity. Can persist for years before psychosis emerges. Individuals have a 2 to 3 fold increased risk of death from a range of comorbid somatic conditions and suicide, the former attributable to unhealthy lifestyle, predisposition, and antipsychotic medication. Individuals typically smoke, can be overweight or obese, suffer from hypertension, dyslipidemias, metabolic syndrome, and diabetes.

E.1.1.1

Medical condition in easily understood language

schizophrenia is a severe long-term mental health condition. It causes a range of different psychological symptoms.

E.1.1.2

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

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	10039626
E.1.2	Term	Schizophrenia
E.1.2	System Organ Class	10037175 - Psychiatric disorders

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 evaluate the efficacy of GWP42003 P versus placebo after 12 weeks of treatment
• To evaluate the safety and tolerability of GWP42003 P

E.2.2

Secondary objectives of the trial

To evaluate the efficacy of GWP42003 P versus placebo based on participant and physician reported outcomes
• To evaluate the pharmacokinetics (PK) of cannabidiol (CBD) and its major circulating metabolites
• To evaluate the PK/pharmacodynamic relationship of GWP42003 P and its major circulating metabolites
• To evaluate the efficacy of GWP42003 P versus placebo based on serum biomarkers
• To evaluate the pharmacogenomic relationship of GWP42003-P versus placebo

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

6.1.1 Male or female 18 to 55 years of age at the time of signing the ICF.
6.1.2 Willing and able to give informed consent for participation in the trial.
6.1.3 BMI of 18 to 40 kg/m2 inclusive and a body weight ≥ 50 kg at screening.
6.1.4 Diagnostic and Statistical Manual of Mental Disorders (DSM 5) diagnosis of schizophrenia, confirmed by the Mini International Neuropsychiatric Interview (MINI) for Psychotic Disorders Studies.
6.1.5 Clinically stable outpatient, based on the investigator’s judgment and defined by no signs of exacerbation of schizophrenia (no hospital admissions or prison incarcerations), and no evidence of an increased level of psychiatric care (including cognitive behavior rehabilitation or individual psychotherapy) within 12 weeks prior to screening.
6.1.6 PANSS T score of ≥ 60 and < 110 at screening and baseline visits.
6.1.7 Score of ≥ 4 for at least 2 of the following PANSS items: delusions (P1), conceptual disorganization (P2), hallucinatory behavior (P3), suspiciousness (P6), somatic concern (G1), or unusual thought content (G9) at screening a visits.
6.1.8 Score ≥ 4 (at least moderately ill) on the CGI S at screening visit.
6.1.9 Undergoing treatment with at least 1 antipsychotic medication with no change in dosing, supported by documentation (including pharmacy records), for at least 8 weeks prior to screening and no change in antipsychotic medication dosing planned throughout the trial.
6.1.10 Taking a maximum of 2 antipsychotic medications. For participants taking oral antipsychotic medications only, the sum of primary and secondary antipsychotic medications is ≤ 30 mg/day of oral olanzapine equivalents. For participants taking long-acting injectable antipsychotic medications, the dose is within the range approved and any secondary oral antipsychotic medications is ≤ 5 mg/day of oral olanzapine equivalents.
6.1.11 Documented response (at least partially) to treatment with current antipsychotic medications (e.g., treatment of recent exacerbation of psychotic symptoms) as assessed by the investigator or treating physician. Documentation can include medical records, pharmacy records, or corroboration in writing by the clinician(s) currently responsible for the participant’s psychiatric treatment.
6.1.12 On a stable dose if taking concomitant psychotropic medications and within allowed limits, including antidepressants, anxiolytics, anticholinergics and/or antiepileptics for at least 4 weeks prior to screening (dose reductions ≤ 25% of total dose are permitted) with no plans to change dosing during the trial (i.e., from screening onwards). Valproic acid or any prescribed valproate product (valproate semisodium or valproate sodium) is disallowed within 4 weeks (i.e., more than 5 half lives) prior to the baseline visit.
6.1.13 Willing to allow the responsible authorities to be notified of participation in the trial, if mandated by local law.

E.4

Principal exclusion criteria

6.2.1 Recent (within the last 3 months prior to screening) diagnosis of panic disorder, depressive episode, or other comorbid psychiatric conditions based on the MINI for Psychotic Disorders Studies (or DSM 5) OR has PANSS item G6 score of ≥ 5 (depression) at screening.
6.2.2 Any psychiatric disorder that may interfere with the conduct of this trial, including but not limited to attention deficit hyperactivity disorder, pervasive developmental disorder, intellectual disability, personality disorder that might interfere with compliance or increase suicidal risk, manic or hypomanic episode, or any other psychotic disorder, as defined in the DSM 5.
6.2.3 Current diagnosis or a history of substance use disorder according to DSM 5 criteria within 6 months prior to screening or prior chronic substance abuse judged likely to recur during the trial period by the investigator. Nicotine use or occasional cannabis use (≤ 3 days per week recreational cannabis use) is acceptable. Corroboration of the participant’s frequency of cannabis use by an adult informant (e.g., family member, social worker, caseworker, residential facility staff, or nurse) should be obtained if the participant has a positive urine test for THC at screening.
6.2.4 A positive drug screen for opiates, methadone, cocaine, amphetamines (including ecstasy), or barbiturates; a repeat drug screen may be done to verify the result.
6.2.5 Any history of suicidal behavior or any suicidal ideation of type 4 or 5 on the adult C SSRS within 1 month prior to screening.
6.2.6 A ± ≥ 20% change in PANSS T score during the placebo run in period (Visit 2 to Visit 3).
6.2.7 Treatment-resistant schizophrenia as judged by the treating physician, and as defined by having previously failed > 2 trials of antipsychotic trial medications at therapeutic doses or required clozapine therapy due to non-response to antipsychotic therapy within the previous 5 years.
6.2.8 Non-compliance, as assessed by antipsychotic medication and the IMP adherence monitoring Platform:
− ≤ 75% compliance of current oral antipsychotic medication during the single-blind, placebo run-in periods (Visit 2 to Visit 3).
− ≤ 75% compliance of current long-acting injectable antipsychotic medication as assessed by number of administrations falling more than 1 week outside of the scheduled due date of administration, in the 6 months prior to screening (Visit 1) and baseline (Visit 3).
− ≤ 75% compliance of IMP during the single-blind, placebo run-in period (Visit 2 to Visit 3) for current IMP.
6.2.9 Based on the investigator assessment, current antipsychotic medication blood levels are below the therapeutic range (only applicable when therapeutic drug monitoring is available for the antipsychotic(s) prescribed for the participant).
6.2.10 History of moderate or severe head trauma (for example, loss of consciousness for more than 15 minutes) or other neurological disorders (including epilepsy), neurodegenerative disorder (Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease, etc.) or
systemic medical diseases that are, in the opinion of the investigator, likely to interfere with the conduct of the trial or confound the trial assessments.
6.2.11 Tardive dyskinesia (TD) that is moderate to severe (i.e., a score of > 21 on the dyskinesia subscale of the ESRS) or requires treatment.
6.2.12 Any other significant disease, disorder, pending court proceedings or social circumstances (e.g., homelessness) which, in the opinion of the investigator, may either put the participant, other participants, or site staff at risk because of participation in the trial, may influence the result
of the trial, or may affect the participant's ability to take part in the trial.
Other
6.2.13 Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP, such as sesame seed oil.
6.2.14 One or more laboratory values outside the normal range, based on the blood or urine samples taken at the screening visit, that are considered by the investigator to be clinically significant; or the
participant has impaired hepatic function at screening, defined as serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 × upper limit of normal (ULN) or total bilirubin (TBL) > 1.5 × ULN or international normalized ratio (INR) > 1.2 (TBL ULN parameter not applicable for participants diagnosed with Gilbert's disease).
6.2.15 Clinically relevant abnormalities in the ECG measured at screening or randomization (including QT interval with Fridericia correction [QTcF] > 450 msec for males and > 470 msec for females, average of 3 measurements).
6.2.16 Positive serology panel (including hepatitis B surface antigen [HBsAg] and hepatitis C virus [HCV] antibody) and/or positive human immunodeficiency virus [HIV] antibody/p24 antigen screens and other presented in Protocol.

E.5 End points

E.5.1

Primary end point(s)

• Mean change from baseline to Week 12 in the following:
 Positive and Negative Symptoms Scale (PANSS) total (PANSS T) score
 PANSS positive subscale (PANSS P) score
 PANSS negative subscale (PANSS N) score
 PANSS general subscale (PANSS G) score
 Clinical Global Impression of Severity (CGI S) score
• Score at Week 12 in the Clinical Global Impression of Improvement (CGI I)
• Changes in body weight, body mass index (BMI), and waist circumference
• Changes in vital sign measurements
• Adverse events (AEs) and adverse drug reactions (ADRs)
• Extrapyramidal symptoms as assessed by the Extrapyramidal Symptom Rating Scale (ESRS)
• Clinical laboratory test results
• 12 lead electrocardiogram (ECG) parameters
• Calgary Depression Scale for Schizophrenia (CDSS)
• Suicidality as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)

E.5.1.1

Timepoint(s) of evaluation of this end point

from baseline to Week 12

E.5.2

Secondary end point(s)

Mean change from baseline to Week 12 in the following:
 PANSS Marder factors scores
 Brief Assessment of Cognition for Schizophrenia (BACS)
 Schizophrenia Quality of Life Scale (SQLS)
 Cannabis use survey
• Change in the Patient Global Impression of Change (PGIC) score at Week 12
• Proportion of participants with an improvement from baseline at Week 12 of:
 ≥ 20% in PANSS P score
 ≥ 20% in PANSS T score
 ≥ 30% in PANSS P score
 ≥ 30% in PANSS T score
 ≥ 20% PANSS P score and improvement at Week 12 of ‘minimally’, ‘much’ or ‘very much’ on the CGI I
 ≥ 20% PANSS T score and improvement at Week 12 of ‘minimally’, ‘much’ or ‘very much’ on the CGI I
• Proportion of participants at Week 12 ‘minimally’, ‘much’ or ‘very much’ improved on the CGI I
• PK parameters for CBD, 7 hydroxy cannabidiol (7 OH CBD) and 7 carboxy cannabidiol (7 COOH CBD)
• Explore potential correlations between plasma exposure of GWP42003 P and its major circulating metabolites with markers of efficacy and safety
• Endogenous lysophosphatidylinositol
• Markers of inflammation
• Explore potential change from baseline to Week 12 in plasma gene expression
• Explore potential genetic variants associated with efficacy and safety parameters

E.5.2.1

Timepoint(s) of evaluation of this end point

from baseline to Week 12

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

Yes

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

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

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)

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

Poland

Serbia

Spain

United States

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

last participant last visit or last contact whichever occurs last

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:

366

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

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

187

F.4.2.2

In the whole clinical trial

366

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)

Study drug will not be available to the patients after the trail.

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

2020-10-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-03-24

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2022-03-02

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