| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| For 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. |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
depending on the 4 study phases:
phase A: efficacy based on pain reduction
phase D: maintenance of efficacy based on pain evaluation and by a premature therapy discontinuation due to selected reasons
phase B and C: Safety and adverse reactions based on occurrence of treatment-related AEs/SAEs |
|
| E.2.2 | Secondary objectives of the trial |
in all phases:
potential for dependence and abuse (ABC, diagnosis of substance dependency ICD-10)
Phase A:
change in neuropathic pain symptoms (NPSI)
Phase C and D:
investigation of the effect of abrupt drug withdrawal |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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.
* Drug treatment is indicated if analgesic drug therapy is considered supportive for the realisation 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 optimised 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.
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
7. Understanding of the English 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. The average value of the pain intensity in the morning of the 7 days before visit A2 (study week -1) must be at least 4 points on an 11-point NRS.
The last 7 entries of the pain intensity before visit A2 in the patient diary are used for the calculation (there must be at least 5 pain intensity
readings in the morning from the study week -1)
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 two 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
d2. Patient has experienced a morning pain score improvement of at least 30% in treatment Phase B (mean morning pain score of study Week 43
compared to the mean morning pain score in the 7 days prior to visit A2 (study week -1), there must be at least four values
from study Week 43 and five values from study week -1)
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
participation in Phase D
d7. Patient has taken the study product on at least 5 out of 7 days in study week 43 (daily dose at least 1 n) and documented the intake of the study
product in the patient diary. |
|
| E.4 | Principal 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 medicinal 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) currently or in the past, severe depression not due to chronic low back
pain currently or in the past, or individuals at risk of suicide (examined using the MINI questionnaire: when at least one module is fulfilled)
9. Severe mental illness (psychosis, schizophrenia, bipolar disorder, severe depression, anxiety disorder) currently or in the past 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 interventional 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.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Phase A: absolute change from baseline (study week -1) in mean pain intensity at week 15 measured in the morning on the 11-point NRS scale
Phase B: The number and proportion of patients with an AE in phase B that the investigator considers to be related to VER-01, and the number and severity of these AEs
Phase C: The number and proportion of patients with an AE in phase B that the investigator considers to be related to VER-01, and the number and severity of these AEs
Phase D: time to treatment failure, which is the time in days from randomization to Phase D (R2) until the first day of treatment failure. Therapy failure is assessed by the daily calculated 7-day mean value of the NRS pain score in the morning during the treatment period, which must have deteriorated by at least 20% and at least 1 point compared to baseline (mean value of the morning pain score in study week 43). The first day within this seven-day window for which this criterion is fulfilled is subsequently defined as the first day of treatment failure. Furthermore, treatment failure is defined as an early discontinuation of treatment for selected reasons
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase A: patient diary: daily in the morning
Phase B: B7-B10, AID1-4
Phase C: C11-C14, AID5-8
Phase D: patient diary, daily in the morning (treatment period)
|
|
| E.5.2 | Secondary end point(s) |
1) absolute change compared to baseline NPSI total score in patients with neuropathic pain
2) Pain-Responder (30% and 50%) in the morning, as well as in the morning and the evening on average
3) Sleep quality (NRS)
4) Sleep quality (MOS-SS)
5) Intake of rescue and concomitant medication
6) Depression, anxiety and stress (DASS)
7) Global assessment of the complaints by the patient (PGIC)
8) Satisfaction with the treatment result - patient
9) Satisfaction with treatment tolerance - patient
10) Satisfaction with the treatment result - investigator
11) Safety and side effects
12) Quality of life (SF-36)
13) Physical disability caused by low back pain (RMD)
14) Dependence (ABC)
15) Diagnosis substance dependency (ICD-10)
16) Symptoms of drug withdrawal (CWS)
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) A1-A6, B8-B10, C11-C14, D15, D16
2) daily through patient diary
3) daily through patient diary
4) A2, A3, A4, A5, A6
5) A2-A6, B7-B10, C1-C13
6) weekly through patient diary
7) A6, B10, C13, D11
8) A6, B10, C13, D11
9) A6, B10, C13, D11
10) A6, B10, C13, D11
11) A1-A6, D11-D12
12) A2-A6, B10, C13, D11
13) A1, A2, A6
14) A3-A6, B7-B10, C11-C13, D11
15) C13, D11
16) daily through patient diary (phase C: wash-out phase, phase D: treatment phase and wash-out phase)
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| different phases: open label and double-blind, randomized, placebocontrolled phases |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 90 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 100 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 10 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 10 |
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