Dose-Response Evaluation of Dronabinol (VER-01) in Chronic Non-Specific Low Back Pain Unresponsive to Non-Opioid Analgesics

The primary objective of this study is to characterize the **dose-response** relationship of VER-01 in terms of pain reduction in patients with chronic non-specific low back pain. This is particularly relevant when drug treatment is indicated, and previous optimized treatments with non-opioid analgesics have not provided sufficient pain relief or were unsuitable due to contraindications or intolerance. Understanding the dose-response relationship is crucial for optimizing therapeutic strategies and improving patient outcomes in managing chronic pain conditions.

The secondary objectives include evaluating the efficacy of VER-01 using additional outcome measures, assessing the safety profile, including the potential for dependency and abuse, and determining the tolerability of VER-01 compared to placebo. These secondary objectives are essential for ensuring the comprehensive evaluation of VER-01's therapeutic potential and safety in the target patient population.

The clinical trial involves a total of **284 participants** who are being studied for the treatment of **chronic non-specific low back pain**. The study population includes both male and female subjects aged **18 years and older**. Participants were selected based on their chronic pain condition, specifically those who have not achieved sufficient pain relief from previous optimized treatments with non-opioid analgesics or for whom such treatments were unsuitable due to contraindications or intolerance. The trial population is characterized by individuals who meet the Quebec Task Force classification system of categories 1 to 3 of low back pain. Participants are required to refrain from using any prohibited medications during the trial, except for rescue medication. The study includes individuals who are willing to comply with scheduled visits and trial-related procedures, and who have provided informed consent. Lifestyle considerations such as ongoing non-drug therapies, like exercise or behavioral therapy, are to be continued unchanged during trial participation. The trial does not specifically exclude any vulnerable populations, indicating a broad inclusion of eligible participants.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the dose-response relationship of the full-spectrum Cannabis Extract VER-01 in patients with chronic non-specific low back pain. The trial will involve multiple centers and is expected to commence recruitment on March 1, 2024, with an estimated completion date of July 31, 2025. The trial will span a total duration of approximately 17 months, including recruitment and follow-up periods. Participants will be randomly assigned to receive either the investigational product, VER-01, or a placebo, with the primary objective being the assessment of pain reduction as measured by a numerical rating scale (NRS).

Study visits are structured to ensure comprehensive monitoring and data collection. The initial visit, known as the inclusion or screening visit, will confirm eligibility based on criteria such as age, pain intensity, and previous treatment history. Participants must meet the Quebec Task Force classification system for low back pain and provide informed consent. Following the screening, eligible participants will enter the treatment phase, which lasts for 7 weeks. During this phase, participants will attend regular follow-up visits to assess pain intensity, medication adherence, and any adverse events. The primary endpoint is the change in mean pain intensity from baseline to the end of the treatment phase.

The end-of-study visit will occur at the conclusion of the treatment phase, where final assessments will be conducted, including the evaluation of any treatment-emergent adverse events and the overall effectiveness of the intervention. Participants are expected to be involved in the study for a total of 15 weeks, including a wash-out phase if necessary. Conditions that may lead to early termination from the study include non-compliance with the study protocol, the occurrence of serious adverse events, or withdrawal of consent by the participant. The trial will adhere to strict ethical guidelines, ensuring the safety and well-being of all participants throughout the study duration.

The clinical trial involves the administration of several treatments, including the experimental medication **VER-01**, which is an **oral solution** containing the active substance **dronabinol**. The maximum daily dose of VER-01 is 2.21 ml, and it is administered orally. The treatment period for VER-01 is up to 15 days. This medication is being tested to evaluate its dose-response relationship in terms of pain reduction in patients with chronic non-specific low back pain.

In addition to the experimental treatment, the trial includes the use of **VER-01 Placebo**. The placebo is used as a control to assess the efficacy of the experimental treatment. The pharmaceutical form and administration details of the placebo are not specified.

Participants in the trial may also receive **ibuprofen**, which is available in various pharmaceutical forms, including film-coated tablets, coated tablets, and capsules. The active substance, ibuprofen, is administered orally with a maximum daily dose of 2400 mg. The treatment period for ibuprofen is also up to 15 days. It serves as an analgesic to manage pain symptoms.

**Paracetamol** is another non-experimental treatment used in the study. It is available in several forms, such as tablets, effervescent tablets, granules, and coated tablets. Paracetamol is administered orally with a maximum daily dose of 3000 mg, and the treatment period is up to 15 days. It is used as an analgesic to provide pain relief.

Additionally, **pantoprazole** is included in the trial as a non-experimental treatment. It is provided in the form of enteric-coated tablets and is administered orally. The maximum daily dose of pantoprazole is 20 mg, with a treatment period of up to 15 days. Pantoprazole acts as a proton pump inhibitor to manage gastric acid-related symptoms that may arise during the trial.

Efficacy in this clinical trial will be assessed primarily through the change in mean pain intensity, measured on an 11-point numerical rating scale (NRS), from Baseline (Week -1) to the end of the Treatment Phase (Week 7). This primary endpoint will provide a quantitative measure of pain reduction in patients with chronic non-specific low back pain. Secondary endpoints include several additional measures: the change in mean pain intensity at the end of the Treatment Phase compared to Baseline in a subgroup of patients with a painDETECT score greater than 18, and the number and percentage of patients achieving 30% and 50% pain reduction at the end of the Treatment Phase compared to Baseline. Furthermore, the trial will evaluate the change in mean chronic low back pain interference with sleep, also measured on an 11-point NRS, and the number and percentage of patients with a 30% and 50% improvement in this score.

Additional secondary endpoints include the number of days with intake of rescue medication, cumulative dose, and relative cumulative dose of rescue medication. Patient-reported outcomes will be assessed using the patient global impression of change (PGIC) with a 7-point Likert scale at Visit 4, and the satisfaction with tolerability will be evaluated on a 5-point Likert scale. The occurrence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) will also be monitored. The trial will assess the occurrence of addictive behavior using the Addiction Behaviors Checklist (ABC) at Visits 3, 4, and 5, and symptoms of abrupt drug withdrawal will be evaluated using the Study Medication Withdrawal Questionnaire Version 2 (SMWQ V2) during the Wash-out Phase.