Phase 1/2 Evaluation of Synthetic Cannabinoid ART27.13 for Cancer Anorexia and Weight Loss in Oncology Patients

Trial ID: 2024-518177-33-00
Protocol: ART27.13-100
Sponsor: Artelo Biosciences Limited

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Diseases & Conditions

Decreased appetite

Objectives

The primary objective of this Phase 1/2 trial is to determine the point estimates of activity of the synthetic cannabinoid **ART27.13** in patients with **cancer anorexia** and weight loss. This will be assessed in terms of weight gain, lean body mass, Karnofsky Performance Status (KPS), and improvement of anorexia at the Stage 2 doses over 4, 8, and 12 weeks, with intrapatient dose escalation at 4-week intervals. Clinically, this is significant as it aims to address the debilitating effects of cancer anorexia, which can severely impact patient outcomes and quality of life.

Secondary objectives include:

Continuing to assess the safety profile of **ART27.13** in patients with cancer anorexia.
Assessing the quality of life (QoL) of patients.

Participants

The clinical trial involves a total of **33 participants** diagnosed with **cancer anorexia**. The study population includes both male and female subjects, aged 18 years and older, who are not considered part of a vulnerable population. Participants were selected based on their documented cancer diagnosis, self-reported anorexia, and unintentional weight loss exceeding 5% of body weight over the past six months. They are required to have a Karnofsky Performance Status (KPS) greater than 50 and an estimated life expectancy of at least 12 weeks. The trial excludes individuals currently undergoing anti-cancer therapy unless they are on a stable dosing regimen. Participants must have adequate hematological, renal, and hepatic function as determined by specific laboratory values. Lifestyle considerations include the requirement for participants to refrain from driving or operating heavy machinery during the initial four weeks of treatment due to potential adverse effects such as dizziness and somnolence. Both men and women of child-bearing potential must agree to use contraceptive measures during the study and for six months following the last treatment. The sponsor has not provided additional information regarding specific lifestyle factors such as diet or physical activity.

Plans and Procedures

The clinical trial is designed as a **randomized**, **double-blind**, and **controlled** study to evaluate the efficacy and safety of the synthetic cannabinoid ART27.13 in patients with **cancer anorexia** and weight loss. The trial is structured in two phases, Phase 1 and Phase 2, with the primary objective of determining the activity of ART27.13 in terms of weight gain, lean body mass, Karnofsky Performance Status (KPS), and improvement of anorexia over a 12-week period. The study involves intrapatient dose escalation at 4-week intervals, with some patients receiving a stable dose of 650 µg for the entire duration.

Participants will be involved in the trial for an estimated duration of 12 weeks, with the overall trial expected to conclude by June 30, 2025. The study visits are sequenced as follows: an initial **screening** visit to assess eligibility based on inclusion criteria, followed by baseline assessments. Subsequent visits occur at 4, 8, and 12 weeks to monitor changes in lean body mass, anorexia, and KPS, using tools such as DEXA scans and visual analog scales. The end-of-study visit will include a comprehensive evaluation of the primary and secondary endpoints, including safety assessments and quality of life measures.

Participants are expected to adhere to the study visit schedule and protocol requirements, including refraining from driving or operating heavy machinery during the first 4 weeks of treatment due to potential adverse effects such as dizziness and somnolence. Conditions that may lead to early termination from the study include significant adverse events, non-compliance with the protocol, or withdrawal of consent. The trial's primary endpoints focus on changes in lean body mass, anorexia, and KPS, while secondary endpoints assess the safety profile of ART27.13 and quality of life improvements.

Treatment

The clinical trial involves the administration of **ART27.13**, a synthetic cannabinoid, as the experimental medication. **ART27.13** is formulated as a hard capsule and is administered orally. The active substance in **ART27.13** is **N-{2-tert-butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-1,3-benzodiazol-5-yl}ethane-1-sulfonamide**, a chemical compound developed by Artelo Biosciences Limited. The trial protocol includes an intrapatient dose escalation at 4-week intervals, with initial dosing at a stable dose of 650 µg for the entire 12-week duration for patients enrolled prior to design changes. The primary objective is to assess the activity of **ART27.13** in terms of weight gain, lean body mass, Karnofsky Performance Status (KPS), and improvement of anorexia in patients with cancer anorexia and weight loss.

The study also includes a **placebo** group to serve as a comparator treatment. The **placebo** is also provided in the form of a hard capsule and is administered orally. It is an inert substance, ensuring that any observed effects in the experimental group can be attributed to the active compound in **ART27.13**. The placebo is manufactured by Artelo Biosciences Limited and is designed to be structurally diverse from the active treatment, ensuring blinding in the trial.

Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol. The trial design allows for a comprehensive evaluation of the therapeutic potential of **ART27.13** in the target patient population, with the placebo group providing a baseline for comparison. The study is conducted under strict regulatory standards to ensure the safety and efficacy of the investigational product.

Efficacy

Efficacy in this clinical trial will be assessed through several primary and secondary endpoints. The primary endpoints include changes in lean body mass, which will be measured by weight and DEXA scans at weeks 4, 8, and 12. Additionally, changes in **anorexia** will be evaluated using a visual analog scale (VAS) and the Functional Assessment of Anorexia Cachexia Therapy (FAACT) questionnaire. The Karnofsky Performance Status (KPS) will also be monitored for changes over the course of the trial.

Secondary endpoints focus on safety and quality of life. Safety will be assessed by analyzing the type, frequency, and severity of adverse drug effects, as determined by reporting adverse events (AEs) and evaluating routine chemistry and hematologic values, urinalyses, vital signs, and electrocardiograms. Quality of life will be assessed using several validated questionnaires, including the FAACT, the patient-generated subjective global assessment (PG-SGA), the EORTC QLQ-C15-PAL, and the revised Edmonton Symptom Assessment Scale (ESAS-r).

The trial involves intrapatient dose escalation at 4-week intervals, with efficacy parameters collected at specified timepoints of 4, 8, and 12 weeks. The study aims to determine point estimates of activity of the investigational product, ART27.13, in patients with cancer anorexia and weight loss. The trial is designed to provide comprehensive data on both the efficacy and safety of ART27.13, contributing to the understanding of its potential benefits in the target patient population.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Have cancer (except those excluded by the exclusion criteria) documented by histopathology or cytology.
Have anorexia as determined by self-reported decrease or lack of appetite or aversion to food.
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.
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.
Estimated life expectancy of at least 12 weeks as judged by the Investigator based on clinical impression.
Have a KPS of > 50
At least 18 years of age at the time of enrollment.
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)
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.
Understand and voluntarily sign and date an Informed Consent Document (ICD) prior to any study related assessments/procedures.
Willing and able to adhere to the study visit schedule and other protocol requirements.
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.

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Exclusion Criteria

Primary brain tumors or symptomatic brain metastases.
Unable to swallow food or medication capsules.
Patients with oral mucositis or oral fungal infection causing anorexia or impairing taste.
Have a disorder that causes obstruction of the gastrointestinal tract or limits the absorption of calories such as bowel obstruction or celiac disease.
Receiving tube feedings or parenteral nutrition.
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.
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
Corticosteroids are allowed if on a stable or tapering dose for 2 weeks prior to enrollment. Patients taking inhaled corticosteroids are permitted.
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.
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.
Pregnant or breast feeding.
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.
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.
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.
Major surgery within 2 weeks prior to enrollment.
Any comorbid condition that confounds the ability to interpret data from the study as judged by the Investigator or Medical Monitor.
Known human immunodeficiency virus infection, acute or chronic hepatitis B, or acute hepatitis C infection.
Clinically significant ascites requiring or expected to require paracentesis.
Corrected QT intervals (QTc) intervals calculated according to Fridericia’s formula (QTcF) >480 ms.
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)
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.
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.
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