Clinical trial NCT04940741: Efficacy and Safety of VER-01 in the Treatment of Patients With Chronic Non-specific Low Back Pain
Official title: Proof of Efficacy, Maintenance of Efficacy, Long-term Safety and Investigation of the Potential for Dependence and Abuse and the Effect of Abrupt Drug Withdrawal of VER-01 in the Treatment of Patients With Chronic Non-specific Low Back Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Non-specific Low Back Pain
Lead sponsor: Vertanical GmbH
Sponsor class: INDUSTRY
First posted: 2021-06-28
Enrollment: 820
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase A: randomised, double-blind, placebo-controlled (Efficacy and safety) Phase B: Open-label treatment (long-term safety) Phase C: Open-label treatment (long-term safety) Phase D: randomised, double-blind, placebo-controlled (maintenance of efficacy)
Primary purpose: TREATMENT

Brief summary: Analysis of the efficacy, maintenance of efficacy, long-term safety, and investigation of the potential for dependence and abuse and the effect of abrupt drug withdrawal of VER-01 in the treatment of patients with chronic non-specific low back pain when drug treatment is indicated and previous optimised treatments with non-opioid analgesics have not led to sufficient pain relief or were unsuitable due to contraindications or intolerance.

Detailed description: The study is divided into four phases: Phase A, B, C and D. All patients who have completed Phase A and for whom the investigator considers further participation to be safe shall begin Phase B. Phases C and D run in parallel, so that patients who have completed Phase B and for whom the investigator considers further participation to be safe can be assigned to one of the two phases.

Phases A and D follow a double-blind, placebo-controlled design, while Phase B and C have an open-label design.

The main goal of Phase A is to demonstrate the efficacy of VER-01 compared to placebo. In Phase B and C the main goal is the investigation of long-term safety of VER-01. In Phase D the primary objective is to demonstrate the maintenance of efficacy of VER-01 on a placebo-controlled basis.

The potential for dependence and abuse will be analyzed in all Phases (A,B,C,D), while the effect of abrupt drug withdrawal of VER-01 will be analyzed in Phase C and D.

Eligibility criteria: Inclusion Criteria:

1. Male and female patients (18 years and older)
2. Chronic (for at least three months) non-specific pain in the lower back (between the lower ribcage and the gluteal folds)
3. Pain intensity on average at least 4 points on an 11-point NRS (one month before the start of the study)
4. Patients with indicated drug treatment where previous optimised treatments with non-opioid analgesics have not led to sufficient pain relief or were unsuitable due to contraindications or intolerance.
5. Willingness of both men and women to use a reliable method of contraception during study participation and for three months after taking the last dose of the IMP
6. Signed patient information and informed consent form is available
7. Understanding of the German language, ability to give consent and compliance
8. The patient has understood the instructions to avoid changes in lifestyle and dietary habits
9. The patient has understood the principle of the patient diary and gives their consent to keep it as instructed

Additional for Phase A

a1. Pain intensity averaged at least 4 points on an 11-point NRS (there must be at least 5 pain intensity readings in the morning from the run-in phase)

a2. Willingness not to take any analgesic medication (non-opioid and opioid analgesics as well as adjuvant analgesics) during participation in study Phase A (except rescue medication)

a3. Willingness to continue a current non-drug therapy unchanged as planned during participation in Phase A

Additional for Phase B

b1. Previous and complete participation in Phase A until and including Visit A6

b2. Patient wishes to participate voluntarily in the long-term study

b3. From the investigator's point of view, further participation is considered medically safe

b4. Willingness not to take any additional analgesic medication (non-opioid and opioid analgesics as well as adjuvant analgesics) during the last three weeks of study Phase B (except rescue medication).

Additional for Phase C

c1. Previous and complete participation in Phase B until and including Visit B10

c2. Patient wishes to participate voluntarily in the long-term study

c3. From the investigator's point of view, further participation is considered medically safe

Additional for Phase D

d1. Previous and complete participation in Phase B until and including Visit B10 (patients received Ver-01 for 26 weeks)

d2. Patient has experienced a pain score improvement of at least 30% in treatment Phase B (mean value of the study week 43 compared to the mean value of the run-in phase, there must be at least four values from study week 43 and five values from the run-in phase)

d3. Patient wishes to participate voluntarily in the study

d4. From the investigator's point of view, further participation is considered medically safe

d5. Willingness not to take any analgesic medication (non-opioid and opioid analgesics as well as adjuvant analgesics) during participation in study Phase D (except rescue medication)

d6. Willingness to continue a current non-drug therapy unchanged as planned during study

Exclusion Criteria:

1. Professional groups for which the ability to operate machinery and drive vehicles is the primary activity (including truck, bus and forklift drivers, pilots)
2. Alcohol/drug/medication abuse and previous or current intake of methadone in the patient's medical history or suspected by the investigator
3. Intake of analgesic medication (non-opioid and opioid analgesics as well as adjuvant analgesics) within seven days prior to the start of the study
4. Taking cannabis-based products within 30 days prior to the start of the study
5. HIV, dementia (which impairs the assessment of symptoms)
6. Severe forms of the following diseases: Anaemia,hematological/autoimmune/endocrinal/ renal/hepatic/respiratory/cardiovascular or gastrointestinal diseases, symptomatic peripheral vascular diseases
7. Cardiovascular event in the past three months, poorly managed high blood pressure, untreated hypothyroidism, patients with Crigler-Najjar syndrome or Rotor syndrome, surgery within the past two months
8. Severe mental illnesses (e.g. psychosis, schizophrenia, bipolar disorder), severe depression that is not due to the chronic non-specific low back pain, or individuals at risk of suicide (examined using the MINI questionnaire)
9. Severe mental illness (psychosis, schizophrenia, bipolar disorder, severe depression, anxiety disorder) in a first-degree relative (parents and children); suicide in a first-degree relative (parents and children)
10. Patients with an active cancer or tumor-related pain or severe pain due to physical injury
11. Other painful comorbidities, excluding low back pain, that could interfere with the patient's evaluation during the study or the assessment of pain
12. Well-known strong adverse events in connection with cannabis consumption before the start of the study
13. Known allergy to cannabis and/or sesame seeds and products derived from them
14. Known hypersensitivity to the ingredients of the rescue medication
15. Planned blood donation, planned sperm or egg donation, planned freezing of eggs or sperm
16. Pregnancy, breastfeeding, desire to have children (within the next 20 months)
17. Participation in another clinical trial within the past 30 days before the start of the study
18. Inability to give consent, care dependency, patient has a legal guardian/caregiver, or is immobile
19. The patient is in need of special protection (e.g., incarcerated; institutionalized by a court or judicial authority; in a dependent or employment relationship with the sponsor, an external service provider of the sponsor (who is involved in the study conduct), the investigator, or the study site).

Additional for Phase A:

a1. In the case of a current non-drug therapy (e.g. physical or behavioural therapy, acupuncture,massage, thermotherapy), which significantly modulates the perception of pain, it was not maintained unchanged for at least eight weeks prior to study participation in Phase A.

Additional for Phase D

d1. Intake of additional analgesic medication (non-opioid and opioid analgesics as well as adjuvant analgesics) within 21 days prior to the start of study Phase D (except rescue medication).

d2. In the case of a current non-drug therapy (e.g. physical or behavioural therapy, acupuncture,massage, thermotherapy) that significantly modulates the perception of pain, it was not maintained unchanged for at least nine weeks prior to the start of study Phase D.

Primary outcomes:
measure: Phase A: Efficacy based on pain reduction
timeFrame: Baseline up to 15 weeks
measure: Phase B: Safety based on occurrence of treatment-related AEs/SAEs
timeFrame: Up to 29 weeks
measure: Phase C: Safety based on occurrence of treatment-related AEs/SAEs
timeFrame: Up to 28 weeks
measure: Phase D: Maintenance of efficacy
timeFrame: Up to 4 weeks (from date of randomization R2 until the first day of treatment failure)
Secondary outcomes:
measure: Phase A, B, C, D: Mean change in neuropathic pain
timeFrame: Day 1, day 106, day 309, day 351, day 505
measure: Phase A, B, C, D: Change in pain intensity in the morning, as well as in the morning and evening
timeFrame: Baseline up to 72 weeks
measure: Phases A, B, C and D: Pain responders (30 percent and 50 percent) in the morning, as well as in the morning and evening
timeFrame: Baseline up to 72 weeks
measure: Phases A, B, C and D: Sleep quality (NRS)
timeFrame: Baseline up to 72 weeks
measure: Phase A: Sleep quality (MOS-SS)
timeFrame: Day 1, Day 22, Day 50, Day 78, Day 106
measure: Phase A: Intake of rescue and concomitant medication
timeFrame: Up to 16 weeks
measure: Phase D: Intake of rescue and concomitant medication
timeFrame: Up to 6 weeks
measure: Phases A, B, C and D: Depression Anxiety Stress Scales (DASS)
timeFrame: Baseline up to 72 weeks
measure: Phases A, B, C and D: Global assessment of symptoms (patient global impression of change, PGIC)
timeFrame: Day 106, day 309, day 491, day 337
measure: Phases A, B, C and D: Satisfaction with the treatment result - patient
timeFrame: Day 106, day 309, day 491, day 337
measure: Phases A, B, C and D: Satisfaction with the treatment result - investigator
timeFrame: Day 106, day 309, day 491, day 337
measure: Phases A, B, C and D: Satisfaction with tolerability - patient
timeFrame: Day 106, day 309, day 491, day 337
measure: Phase A: Safety and adverse reactions
timeFrame: Up to 16 weeks
measure: Phase D: Safety and adverse reactions
timeFrame: Up to 6 weeks
measure: Phases A, B, C and D: Quality of life scores (Short Form 36, SF-36)
timeFrame: Day 1, day 22, day 50, day 78, day 106, day 309, day 491, day 337
measure: Phases A, B, C and D: Quality of life absolute changes (Short Form 36, SF-36)
timeFrame: Day 1, day 22, day 50, day 78, day 106, day 309, day 491, day 337
measure: Phase A: Scores in bodily function and impairment due to low back pain (Roland Morris Disability Questionnaire, RMD)
timeFrame: Day 1, day 22, day 106
measure: Phase A: Absolute changes in bodily function and impairment due to low back pain(Roland Morris Disability Questionnaire, RMD)
timeFrame: Day 1, day 22, day 106
measure: Phases A, B, C and D: Addiction (Addiction Behaviors Checklist ,ABC)
timeFrame: Day 22, day 50, day 78, day 106, day 127, day 183, day 239, day 309, day 365, day 421, day 491, day 337
measure: Phase C: Diagnosis of substance dependence ICD-10 (International Statistical Classification of Diseases and Related Health Problems)
timeFrame: Day 491
measure: Phase A, B, C and D: Adverse events (AEs)
timeFrame: Through study completion, up to 72 weeks
measure: Phase C: Withdrawal symptoms (Cannabis Withdrawal Scale, CWS)
timeFrame: Up to 2 weeks
measure: Phase D: Withdrawal symptoms (Cannabis Withdrawal Scale, CWS)
timeFrame: Up to 4 weeks
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Emovis GmbH
Study officials:
affiliation: Schmerzzentrum Bonn
name: Joachim Nadstawek, Prof.
role: PRINCIPAL_INVESTIGATOR
References: