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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Artelo Biosciences Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Oct 2021 → ongoing

Decision date (initial)

2024-11-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518177-33-00

EudraCT number

2020-000464-27

ISRCTN

ISRCTN15607817

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

Determine point estimates of activity of ART27.13 in terms of
weight gain, lean body mass, KPS, and improvement of anorexia
at the Stage 2 doses at 4, 8, and 12 weeks with intrapatient dose
escalation at 4-week intervals. Those patients who are enrolled
prior to the design changes being implemented will be dosed at
a stable dose of 650µg for the entire 12 week duration.

Secondary objectives 2

1. Continue to assess the safety profile of ART27.13 in patients with cancer anorexia.
2. Assess QoL of patients.

Conditions and MedDRA coding

Cancer Anorexia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

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 and a continuous downward trend of weight loss in the past 6 months (± 2 weeks) dating back from the date of enrollment.
4. Patients are on either: 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 stable dosing from 2 weeks before enrollment and expected to be on such therapy for another 12 weeks of anti-cancer therapies.
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 × 109/L • Platelets ≥ 75 × 109/L • Serum creatinine ≤ 1.5 times upper limit of laboratory normal (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 (ICD) prior to any study related assessments/procedures.
11. Willing and able to adhere to the study visit schedule and other protocol requirements.
12. Agree to not driving or operating heavy machinery for the first 4 weeks of treatment or longer if AEs warrant, as known AEs of ART27.13 include dizziness and somnolence.

Exclusion criteria 23

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. Be on, been on within 4 weeks prior to enrollment, or expected to be on medications that are known to be strong cytochrome P450 (CYP3) A4 inhibitors or inducers
8. Corticosteroids are allowed if on a stable or tapering dose for 2 weeks prior to enrollment. Patients taking inhaled corticosteroids are permitted.
9. 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.
10. 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.
11. Pregnant or breast feeding.
12. Clinically significant, recent depression requiring the start of antidepressant medications within 4 weeks prior to enrollment. Patients who are already stable on antidepressant medication are permitted.
13. 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.
14. 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.
15. Major surgery within 2 weeks prior to enrollment.
16. Any comorbid condition that confounds the ability to interpret data from the study as judged by the Investigator or Medical Monitor.
17. Known human immunodeficiency virus infection, acute or chronic hepatitis B, or acute hepatitis C infection.
18. Clinically significant ascites requiring or expected to require paracentesis.
19. Corrected QT intervals (QTc) intervals calculated according to Fridericia’s formula (QTcF) >480 ms.
20. 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 certain anti-cancer therapy is allowed)
21. 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.
22. 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.
23. Patients who have previously participated in a study with ART27.13 would be excluded. Patients who fail screening can be rescreened a maximum of 1 time if the Investigator believes that the reason for screen failure may resolve

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Change in lean body mass as determined by weight and DEXA scans at 4, 8, and 12 weeks.
2. Change in anorexia as determined by a visual analog scale (VAS) and (FAACT) questionnaire.
3. Change in KPS.

Secondary endpoints 2

1. Safety: 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.
2. Quality of Life: Assess QoL using the Functional Assessment of Anorexia Cachexia Therapy (FAACT), the patientgenerated subjective global assessment (PG-SGA), the EORTC QLQ-C15-PAL, and revised Edmonton Symptom Assessment Scale (ESAS-r) questionnaires

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Artelo Biosciences Limited

Sponsor organisation

Artelo Biosciences Limited

Address

Mereside, Alderley Park Alderley Park

City

Macclesfield

Postcode

SK10 4TG

Country

United Kingdom

Scientific contact point

Organisation

Artelo Biosciences Limited

Contact name

Paula Daunt

Public contact point

Organisation

Artelo Biosciences Limited

Contact name

Paula Daunt

Locations

2 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 43 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications