Clinical Trials Register

Summary
EudraCT Number:	2020-000464-27
Sponsor's Protocol Code Number:	ART27.13-100
National Competent Authority:	Ireland - HPRA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-07-06
Trial 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

Ireland - HPRA

A.2

EudraCT number

2020-000464-27

A.3

Full title of the trial

A Phase 1/2 Trial of the Synthetic Cannabinoid ART27.13 in Patients with Cancer Anorexia and Weight Loss

A.3.1

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

A Phase 1/2 clinical trial of ART27.13 in patients with a lack or loss of appetite and weight loss due to having cancer.

A.3.2

Name or abbreviated title of the trial where available

ART27.13 in Patients with Cancer Anorexia and Weight Loss

A.4.1

Sponsor's protocol code number

ART27.13-100

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	Artelo Biosciences Limited
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	Artelo Biosciences Limited
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	Aptus Clinical Ltd
B.5.2	Functional name of contact point	Clinical Project Manager
B.5.3	Address:
B.5.3.1	Street Address	Mereside, Alderley Park,
B.5.3.2	Town/ city	Alderley Edge, Cheshire
B.5.3.3	Post code	SK10 4TG
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	0044 1625 238662
B.5.6	E-mail	Joanne.henderson@aptusclinical.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	ART27.13 200µg
D.3.4	Pharmaceutical form	Capsule, hard
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	INN not applied for
D.3.9.1	CAS number	881413-29-2
D.3.9.2	Current sponsor code	ART27.13
D.3.9.3	Other descriptive name	N‐{2‐tert‐butyl‐1‐[(4,4‐difluorocyclohexyl)methyl] ‐1H‐1,3‐benzodiazol‐5‐yl}ethane‐1‐sulfonamide
D.3.9.4	EV Substance Code	SUB217019
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
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	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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	ART27.13 50µg
D.3.4	Pharmaceutical form	Capsule, hard
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	INN not applied for
D.3.9.1	CAS number	881413-29-2
D.3.9.2	Current sponsor code	ART27.13
D.3.9.3	Other descriptive name	N‐{2‐tert‐butyl‐1‐[(4,4‐difluorocyclohexyl)methyl] ‐1H‐1,3‐benzodiazol‐5‐yl}ethane‐1‐sulfonamide
D.3.9.4	EV Substance Code	SUB217019
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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	Capsule
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
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

Cancer anorexia and weight loss

E.1.1.1

Medical condition in easily understood language

Lack or loss of appetite and weight loss associated with cancer.

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

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	10002646
E.1.2	Term	Anorexia
E.1.2	System Organ Class	10027433 - Metabolism and nutrition 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

Stage 1 (Phase 1) -Primary Objectives
• Determine the safety profile of ART27.13 in patients with cancer anorexia at different doses.
• Determine dose-limiting toxicity, if any, within the range of doses used during the first cycle after the first dose of ART27.13.
• Determine the most effective, safe dose (recommended Phase 2 dose, or RP2D) to be used in Stage 2.

Stage 2 (Phase 2): Primary Objectives
• Determine point estimates of activity of ART27.13 in terms of weight gain, lean body mass, KPS, and improvement of anorexia at the RP2D at 12 weeks.

E.2.2

Secondary objectives of the trial

Stage 1 (phase 1): Secondary Objectives
• Assess the activity of ART27.13 in the patient population in terms of increase in lean body mass, weight gain, and improvement of anorexia.
• Assess quality of life (QoL) of patients.
• Determine the pharmacokinetic profile of ART27.13 in the patient population.
• Assess any change in Karnofsky Performance Status (KPS)

Stage 2 (Phase 2): Secondary Objectives
• Continue to assess the safety profile of ART27.13 in patients with cancer anorexia.
• Assess QoL of patients.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Have cancer (except those excluded by the exclusion criteria) documented by histopathology or cytology.
2. Have anorexia as determined by self-reported decrease or lack of appetite or aversion to food.
3. Have documented, unintentional weight loss of >5% of body weight in the past 6 months dating back from the date of enrollment.
4. Patients are on either:
4.1 no anti-cancer therapy for the 2 weeks before enrollment and are not expected to have anti-cancer therapy for the first 12 weeks after the first dose of ART27.13 (Stage 1) or if in Stage 2, after the start of ART27.13/placebo; or
4.2 stable daily dosing from 2 weeks before enrolment and expected to be on such therapy for another 12 weeks of anti-cancer monotherapy therapy with hormonal therapy for breast, prostate, or uterine cancer or capecitabine for breast or colon cancer.
5. Estimated life expectancy of at least 12 weeks as judged by the Investigator based on clinical impression.
6. Have a KPS of >50.
7. At least 18 years of age at the time of enrollment.
8. Adequate hematological, renal, and hepatic function based on laboratory values obtained within 14 days of randomization:
• Absolute neutrophil count ≥ 1.0 X 10⁹/L
• Platelets ≥ 75 X 10⁹/L.
• Serum creatinine ≤ 1.5 times ULN.
• Total serum bilirubin ≤ 1.5 times ULN ( ≤ 3.0 times ULN if patient has been diagnosed with Gilbert’s syndrome or liver metastases)
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (AP) ≤ 2.5 times ULN (≤ 5.0 times ULN if the patient has been diagnosed with liver metastases)
9. For women of child-bearing potential and for men with partners of child-bearing potential, patient must agree to take contraceptive measures for duration of treatments and for 6 months after last study treatment.
10. Understand and voluntarily sign and date an Informed Consent Document prior to any study related assessments/procedures.
11. Willing and able to adhere to the study visit schedule and other protocol requirements.
12. Willing to avoid sun exposure by using protective measures such as sunscreen, clothing, and sunglasses during therapy because the phototoxicity of ART27.13 has not been studied in animals.
13. Agree to not driving or operating heavy machinery for the first 4 weeks of treatment or longer if adverse events warrant as known adverse events of ART27.13 include dizziness and somnolence.

E.4

Principal exclusion criteria

1. Primary brain tumors or symptomatic brain metastases.
2. Unable to swallow food or medication capsules.
3. Patients with oral mucositis or oral fungal infection causing anorexia or impairing taste.
4. Have a disorder that causes obstruction of the gastrointestinal tract or limits the absorption of calories such as bowel obstruction or celiac disease.
5. Receiving tube feedings or parenteral nutrition.
6. Be on, been on within 4 weeks prior to enrollment, or expected to be on medications that have the potential to affect anorexia or caloric intake. Examples of such medications include any synthetic or natural cannabinoid (inhaled or administered by any other route) and megestrol.
7. Corticosteroids are allowed if on a stable or tapering dose for 2 weeks prior to enrollment. Patients taking inhaled corticosteroids are permitted.
8. History of any recreational or illicit drug use, alcohol misuse, or other drug misuse within the last 24 months. Current illicit drug use or recreational or medicinal use of cannabinoids is also excluded.
9. Known hypersensitivity to ART27.13 or any of its excipients. A list of ingredients of ART27.13 capsules will be provided to sites prior to the start of Stage 1 of the protocol. Prior to the start of Stage 2, the list of ingredients will be provided for placebo.
10. Pregnant or breast feeding.
11. Clinically significant, recent
depression requiring the start of antidepressant medications within 4 weeks prior to enrollment.
12. Condition other than cancer that is active and causing anorexia and/or weight loss such as AIDS, chronic obstructive pulmonary disease, chronic kidney disease, heart failure, or pathological eating disorder.
13. Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous (IV) antibiotics & psychiatric illness/social situations that would limit compliance with study requirements.
14. Major surgery within 2 weeks prior to enrollment.
15. Any comorbid condition that confounds the ability to interpret data from the study as judged by the Investigator or Medical Monitor.
16. Known human immunodeficiency virus infection, acute or chronic hepatitis B, or acute hepatitis C infection.
17. Clinically significant ascites requiring or expected to require paracentesis.
18. Corrected QT intervals (QTc) intervals calculated according to Fridericia’s formula (QTcF) >480 ms.
19. Anticipated need for anti-cancer therapy from 2 weeks prior to enrollment and 12 weeks after the first dose of ART27.13 or in Stage 2 ART27.13/placebo. (Continued use of current daily-dose anti-cancer therapy is allowed.)
20. Investigational agent within 4 weeks prior to enrollment or expected need for an investigational agent for 12 weeks after the first dose of ART27.13 or in Stage 2 placebo.
21. Receiving radiotherapy within 2 weeks dating back from enrollment or anticipated to need radiotherapy within 12 weeks of enrollment. Short term palliative radiation treatment involving a local lesion is allowed.

E.5 End points

E.5.1

Primary end point(s)

Stage 1 Primary Endpoints (Safety):
1. Analysis of the type of, frequency, and severity of adverse drug effects as determined by reported AEs and evaluation of routine chemistry and hematologic values, urinalyses, vital signs, and electrocardiograms.
2. Assessment of type and incidence of dose-limiting toxicity (DLT).
3. Most effective, safe dose (RP2D) to be used in Stage 2. Effectiveness is based primarily on the endpoint of lean body mass and weight gain after the first cycle.

Stage 2 Primary Endpoints (Activity):
• Change in lean body mass as determined by weight and DEXA scans at 12 weeks.
• Change in anorexia as determined by a visual analog scale (VAS) and (FAACT) questionnaire.
• Change in KPS.

E.5.1.1

Timepoint(s) of evaluation of this end point

Stage 1 Primary Endpoints (Safety):
1. AEs: Duration of trial. Chemistry, Hematology, Vital signs: Days pre-dose, 8, 15, 22, 29, 43, 57, 71, EOT, FU. Urinalyses: Days 29, 57, EOT, FU. ECG: Days pre-dose, 8, 15, 22, 29, 43, 57, EOT, FU. [All +/-3 Days except for EOT]
2. DLTs: Reported throughout duration of study.
3. RP2D for Stage 2: Lean body mass and weight gain at 4 weeks.

Stage 2 Primary Endpoints (Activity):
1. DEXA scans: at 12 weeks.
2. VAS: Days pre-dose, 29, 57, EOT, FU. FAACT questionnaire: Days pre-dose, 15, 29, 57, EOT, FU [All +/-3 Days except for EOT]
3. KPS: Days pre-dose, 8, 15, 22, 29, 57, EOT, FU [All +/-3 Days except for EOT]

E.5.2

Secondary end point(s)

Stage 1 Secondary Endpoints (Activity):
1. Change in lean body mass as determined by weight and DEXA scans.
2. Change in anorexia as determined by a visual analog scale (VAS).
3. Assess QoL using the Functional Assessment of Anorexia Cachexia Therapy (FAACT), the patient-generated subjective global assessment (PG-SGA), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL, and revised Edmonton Symptom Assessment Scale (ESAS-r) questionnaires.

Stage 2 Secondary Endpoints (Activity):
(Safety):
1. Assessment of the safety profile of ART27.13 by analyzing the type of, frequency, and severity of adverse drug effects as determined by reporting AEs and evaluation of routine chemistry and hematologic values, urinalyses, vital signs, and electrocardiograms.
(Quality of Life):
2. Assess QoL using the Functional Assessment of Anorexia Cachexia Therapy (FAACT), the patient-generated subjective global assessment (PG-SGA), the EORTC QLQ-C15-PAL, and revised Edmonton Symptom Assessment Scale (ESAS-r) questionnaires.

E.5.2.1

Timepoint(s) of evaluation of this end point

Stage 1 Secondary Endpoints (Activity):
1. Weight: Days pre-dose, 8, 15, 22, 29, 43, 57, 71, EOT, FU. DEXA scans: Days pre-dose, 29, EOT, FU. [All +/-3 Days except for EOT]
2. VAS: Days pre-dose, 29, 57, EOT, FU.
3. FAACT, and ESAS-r questionnaires: Days pre-dose, 15, 29, 57, EOT, FU. The PG-SGA and EORTC QLQ-C15-PAL: Days pre-dose, 15, 22, EOT, FU. [All +/-3 Days except for EOT]
Stage 2 Secondary Endpoints:
1. AEs: Duration of trial. Chemistry, Hematology, Vital signs: Days pre-dose, 8, 15, 22, 29, 43, 57, 71, EOT, FU. Urinalyses: Days 29, 57, EOT, FU. ECG: Days pre-dose, 8, 15, 22, 29, 43, 57, EOT, FU.
2. FAACT, and ESAS-r questionnaires: Days pre-dose, 15, 29, 57, EOT, FU. PG-SGA, EORTC QLQ-C15-PAL questionnaires: Days pre-dose, 15, 29, EOT, FU. [All +/-3 Days except for EOT]

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

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

Yes

E.6.13.1

Other scope of the trial description

Quality of Life

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

dose finding

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

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Phase 1/2 performed in 2 stages: Stage 1 is an ascending dose trial. Stage 2 is a RCT.

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

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

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1