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

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.

The test intervention VER-01 is a cannabis-based pain medication currently under clinical development that is expected to provide adequate pain relief while being better tolerated in long-term treatment compared to opioid analgesics. This study aims to demonstrate the superior tolerability, especially in terms of bowel function, of VER-01 compared to existing authorised and marketed opioid analgesics in patients with chronic non-specific low back pain. In addition, the safety and tolerability as well as the efficacy of VER-01 compared to opioid therapy will be evaluated.

Eligibility Criteria:
Inclusion Criteria:

1. Male and female patients ≥18 years of age
2. Provision of informed consent form voluntarily signed and dated by the patient
3. 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
4. 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
5. 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.
6. 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.
7. 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
8. 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
9. Ongoing additional analgesic treatment prior visit 1 must be continued during the run-in phase
10. Bowel Function Index total score of 28.8 or less at visit 1.

Exclusion Criteria:

1. Patients with a known history of alcohol/drug/medication abuse or dependency and previous or current use of methadone
2. Evidence of drugs of abuse or illegal drugs by urine drug test performed at visit 1
3. Known intolerance or hypersensitivity to ingredients of rescue medication, opioid therapy (assigned by the investigator) and/or VER-01
4. Participation in another clinical interventional study within the last 30 days prior screening visit (visit 1)
5. Occupational groups with primary activity of operating machinery and driving motor vehicles
6. Planned blood donation or planned donation or freezing of sperm or oocytes during study participation and 3 months after end of study participation
7. Pregnant or breastfeeding female patients
8. 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)
9. Known use of opioid or cannabis-based treatments within 30 days before screening visit (visit 1)
10. 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.
11. Start of or planned non-drug pain therapy during run-in phase (physical or behavioral therapy)
12. Start or planned start of an additional analgesic treatment during run-in phase
13. Ongoing monoamine oxidase inhibitor therapy at screening visit (visit 1)
14. 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.
15. Painful comorbidities which could interfere with the low back pain intensity assessment during the study
16. Known history of human immunodeficiency virus (HIV) infection
17. Severe forms of the following diseases: Anaemia, haematological / autoimmune / endocrine / renal / hepatic / respiratory / cardiovascular / neurological / gastrointestinal / symptomatic peripheral vascular diseases.
18. Cardiovascular event in the last three months before screening visit (visit 1)
19. Known uncontrolled hypertension (average systolic blood pressure ≥140 mmHg or average diastolic blood pressure

    ≥90 mmHg) and/or untreated hypothyroidism
20. Patients with Crigler-Najjar syndrome, Rotor syndrome and/or porphyria
21. History of major trauma or back surgery in the last 2 months prior to screening visit (visit 1)
22. Known history of or current severe psychiatric illness
23. 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)
24. Patients with severe respiratory depression
25. Patients with lung disease associated with impaired lung function (e.g., acute or severe bronchial asthma or hypercapnia/respiratory failure).
26. Patients with conditions of increased intracranial pressure due to head injury or disease of the brain.
27. Patients with existing or suspected paralytic ileus
28. Patients with intestinal obstruction due to intestinal paralysis