Comparison of VER-01 to Opioids in Patients With Chronic Non-specific Low Back Pain

Study Overview
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Brief Summary
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Randomized, open-label, parallel-group phase III trial to prove an additional benefit of the full-spectrum cannabis extract VER-01 over opioids in patients with chronic non-specific low back pain for whom drug treatment is indicated and previous optimized treatments with non-opioid analgesics have not led to sufficient pain relief or were unsuitable due to contraindications or intolerance.

Official Title
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Multicentre, Randomized, Open-label Study to Prove an Additional Benefit of the Full-spectrum Cannabis Extract VER-01 Over Opioids in the Treatment of Patients With Chronic Non-specific Low Back Pain.

Conditions
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Chronic Non-specific Low Back Pain

Intervention / Treatment
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* Drug: VER-01
* Drug: Opiod therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients ≥18 years of age Provision of informed consent form voluntarily signed and dated by the patient For women of childbearing potential and men of reproductive potential: use of a reliable contraceptive method (Pearl index < 1) at least 1 month before the start of the study and willingness to use it during the study participation and 3 months after the last intake of the test or comparative intervention Patient understands the local language and is willing and able to comply with scheduled visits, treatment plan, patient diary and other study related procedures throughout study participation Chronic (for at least 3 months) non-specific pain in the lower back (between the 12th thoracic vertebra and lower gluteal folds). Non-specific pain refers to pain without a clear specific treatable cause. Patients with indicated drug treatment* where previous optimized treatments** with non-opioid analgesics (including combinations) have not led to sufficient pain relief or were unsuitable due to contraindications or intolerance. * Drug treatment is indicated if analgesic drug therapy is considered supportive for the realization of activating measures, or if the patient has unbearable functional disabilities as a result of the pain, despite regularly performing these measures. ** Treatment is considered optimized when I. a further increased drug dose is unsuitable from a medical perspective considering side effects and/or II. it is not expected that a higher drug dose would result in a further advantage in terms of efficacy. Low back pain intensity on average at least 4 points on an 11-point Numeric Rating Scale in the last 4 weeks prior visit 1 Ongoing non-drug pain therapy (physical or behavioral therapy) must have been stable for at least 2 weeks prior visit 1 and must be continued during the run-in phase Ongoing additional analgesic treatment prior visit 1 must be continued during the run-in phase Bowel Function Index total score of 28.8 or less at visit 1. Exclusion Criteria: Patients with a known history of alcohol/drug/medication abuse or dependency and previous or current use of methadone Evidence of drugs of abuse or illegal drugs by urine drug test performed at visit 1 Known intolerance or hypersensitivity to ingredients of rescue medication, opioid therapy (assigned by the investigator) and/or VER-01 Participation in another clinical interventional study within the last 30 days prior screening visit (visit 1) Occupational groups with primary activity of operating machinery and driving motor vehicles Planned blood donation or planned donation or freezing of sperm or oocytes during study participation and 3 months after end of study participation Pregnant or breastfeeding female patients Patient is unable to provide written informed consent, in need for care, has a guardian/caretaker, is immobile, or is particularly vulnerable (e.g., imprisoned; institutionalised by a court or judicial authority; dependent or employed by the sponsor, an external service provider of the sponsor (involved in the conduct of the study), the investigator or the trial site) Known use of opioid or cannabis-based treatments within 30 days before screening visit (visit 1) Patients for whom cannabis or opioid therapy is not indicated, e.g., due to a history of non-response to opioid therapy or cannabis-based medicines in the treatment of chronic non-specific low back pain in the past. Start of or planned non-drug pain therapy during run-in phase (physical or behavioral therapy) Start or planned start of an additional analgesic treatment during run-in phase Ongoing monoamine oxidase inhibitor therapy at screening visit (visit 1) Patients with history of cancer in the last 5 years prior to screening visit (visit 1). Except for cutaneous basal cell or squamous cell cancer resolved by excision without recurrence and cervical cancer in situ resolved by excision with negative pap test. Painful comorbidities which could interfere with the low back pain intensity assessment during the study Known history of human immunodeficiency virus (HIV) infection Severe forms of the following diseases: Anaemia, haematological / autoimmune / endocrine / renal / hepatic / respiratory / cardiovascular / neurological / gastrointestinal / symptomatic peripheral vascular diseases. Cardiovascular event in the last three months before screening visit (visit 1) Known uncontrolled hypertension (average systolic blood pressure ≥140 mmHg or average diastolic blood pressure ≥90 mmHg) and/or untreated hypothyroidism Patients with Crigler-Najjar syndrome, Rotor syndrome and/or porphyria History of major trauma or back surgery in the last 2 months prior to screening visit (visit 1) Known history of or current severe psychiatric illness Known history of or current severe depression (not due to chronic low back pain) (assessed by Patient Health Questionnaire - 9) and/or suicidal ideation (assessed by Columbia-Suicide Severity Rating Scale) at screening visit (visit 1) Patients with severe respiratory depression Patients with lung disease associated with impaired lung function (e.g., acute or severe bronchial asthma or hypercapnia/respiratory failure). Patients with conditions of increased intracranial pressure due to head injury or disease of the brain. Patients with existing or suspected paralytic ileus Patients with intestinal obstruction due to intestinal paralysis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test intervention: VER-01<br> | Drug: VER-01<br>* Standardized oleoresin of Cannabis sativa L. folium cum flore, THC-chemotype (cannabis leaves and - flowers), corresponding to 21 mg (-)-trans-Δ9-Tetra-hydrocannabinol (THC) per gram drug product<br>|
| Active Comparator: Comparative intervention: Opioid therapy (with an authorised and marketed opioid, ATC code N02A)<br> | Drug: Opiod therapy<br>* The patient-specific selection of the marketed opioid (based on standard of care and provided for this study) is at the discretion of the investigator and made before randomization (at visit 1) to ensure that the outcome of the randomization does not influence the opioid selection. Preferably oral administration Preferably retarded release preparations Titration and dosage according to SmPC (maximum titration phase 3 weeks) The dosage and the chosen opioid (opioid rotation) can be adapted to the patient's specific needs in the course of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| risk of developing constipation | Number and proportion of constipation responders at the end of treatment phase (visit 9). A constipation responder is defined as a patient with a change from baseline (visit 2) in Bowel Function Index (BFI) total score of at least 15 points at visit 9 and a BFI total score of more than 28.8 at visit 9. | 190 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy based on pain reduction | 1. Number and percentage of 30% pain responders at study week 27 (last week of treatment phase) compared with the baseline score (study week -1) | 190 days | 
| efficacy based on pain reduction | 2. Number and percentage of 30% pain responders in the subgroup of patients with a neuropathic pain component (painDETECT score > 18) at study week 27 compared with the baseline score (study week -1) | 190 days | 
| efficacy based on pain reduction | 3. Number and percentage of patients with a 30% improvement of the mean daily low back pain interference with sleep score evaluated on an 11-point Numeric Rating Scale (NRS) at study week 27 compared with the baseline score (study week -1) | 190 days |