Dose-response characterization of VER-01 in the treatment of patients with chronic non-specific low back pain

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vertanical GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

13 Feb 2024 → 1 Aug 2025

Decision date (initial)

2024-05-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Vertanical GmbH

External identifiers

EU CT number

2023-507358-34-00

ClinicalTrials.gov

NCT06475001

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Therapy, Efficacy

The primary objective is to characterize the dose-response relationship of VER-01 in terms of pain reduction in patients with chronic non-specific low back pain when drug treatment is indicated and a previous optimized treatment with non-opioids has not led to sufficient pain relief or was unsuitable due to contraindications or intolerance.

Secondary objectives 1

1. The secondary objective is to evaluate the efficacy using additional outcome measures, the safety (including the potential for dependency and abuse) and the tolerability of VER-01 compared to placebo.

Conditions and MedDRA coding

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.

Study design 1 period

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002668-PIP01-19

Plan to share IPD

Yes

IPD plan description

not applicable

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Patient meets the Quebec Task Force (QTF) classification system of categories 1 to 3 of low back pain
2. Male and female patients ≥ 18 years of age
3. Provision of informed consent form voluntarily signed and dated by the patient
4. For female patients of childbearing potential and male patients of reproductive potential: use of a reliable contraceptive method (Pearl index < 1) at least 1 month before the start of the trial and willingness to use it during trial participation and 3 months after the last intake of the test or comparative intervention
5. Patient understands the local language and is willing and able to comply with scheduled visits, treatment plan, eDiary, and other trial-related procedures throughout trial participation
6. Chronic (≥ 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 somatic cause, for which targeted therapy can have a positive effect on the course of the disease. Such somatic causes are e.g., herniated vertebral disk, spinal canal stenosis, inflammatory back pain, osteoporosis, fracture, infection, tumor, spondylolisthesis
7. Patients with indicated opioid 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, or if non-drug therapies are not indicated ** 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
8. Low back pain intensity on average ≥ 4 points on an 11-point NRS in the last 4 weeks prior Visit 1 *; *Country specific additional requirement for Czech Republic: Low back pain intensity on average ≤ 8
9. In case of non-drug therapy in the 4 weeks prior to Visit 1 (e.g., exercise or behavioral therapy, acupuncture, massage, thermotherapy) that significantly modulates pain perception: the non-drug therapy was unchanged and is still ongoing at Visit 1 and all requirements for continuation of the therapy throughout the trial are given (e.g., prescription, patient's compliance). Ongoing non-drug therapies should be continued unchanged during trial participation
10. Willingness to not take or use any prohibited medication during trial participation. The intake or use of any additional analgesic medication (non-opioid and opioid analgesics as well as adjuvant analgesics and muscle relaxants), during trial participation is prohibited (except rescue medication). Likewise, strong inhibitors, substrates, or inducers of CYP2C9 and CYP3A4 are considered prohibited concomitant medication in this trial

Exclusion criteria 23

1. Patients with a known history of alcohol/drug/medication abuse (except nicotine) or any dependency or addiction (physical or behavioral) and previous or current use of methadone
2. Evidence of drug abuse or illegal drugs by urine drug test performed at Visit 1
3. Known intolerance or hypersensitivity to ingredients of rescue medication, VER-01, and/or placebo (e.g., sesame oil)
4. Participation in another clinical interventional trial within the last 30 days prior to Visit 1 or previous participation in a trial for VER-01
5. Occupational groups with primary activity of operating machinery and driving motor vehicles
6. Planned blood donation, planned pregnancy, or planned donation or freezing of sperm or oocytes during trial participation and 3 months after end of trial 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; institutionalized by an administrative or judicial authority; dependent or employed by the Sponsor, an external service provider of the Sponsor (involved in the conduct of the trial), the investigator, or the trial site)
9. Known use of THC-containing drugs within 30 days prior to Visit 1
10. Patients deemed non-responsive to cannabis treatment due to medical history
11. Start of or planned start of an analgesic treatment or non-drug therapy, that significantly modulates pain perception, during trial participation
12. Planned surgery or other invasive procedure that requires analgetic treatment or might cause pain that could interfere with the low back pain intensity assessment
13. Patients with history of cancer in the last 5 years prior to 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
14. Painful comorbidities which could interfere with the low back pain intensity assessment during the trial
15. Known history of human immunodeficiency virus (HIV) infection
16. Severe forms of the following diseases: anaemia, haematological/autoimmune/endocrine/renal/hepatic/ respiratory/cardiovascular/neurological/gastrointestinal/ symptomatic peripheral vascular diseases
17. Cardiovascular event within the last 3 months prior to Visit 1
18. Poorly managed high blood pressure and/or untreated hypothyroidism
19. Patients with bilirubin metabolic disorder (e.g., Crigler-Najjar syndrome, Rotor syndrome)
20. Known history of major trauma or back surgery within the last 6 months prior to Visit 1
21. Known history of previous or current severe psychiatric illness
22. Known history of previous 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) or current intake of antidepressants at Visit 1
23. Known history of previous or current epilepsy or seizure disorder

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the change in mean pain intensity measured on a 11-point numerical rating scale (NRS) from Baseline (Week -1) to the end of the Treatment Phase (Week 7 of the Treatment Phase).

Secondary endpoints 9

1. Number and percentage of 30% and 50% pain responders at the end of the Treatment Phase (Week 7 of the Treatment Phase) compared to Baseline (Week -1)
2. Change of mean chronic low back pain interference with sleep evaluated on an 11-point NRS at the end of the Treatment Phase (Week 7 of the Treatment Phase) compared to Baseline (Week -1)
3. Number and percentage of patients with a 30% and 50% improvement of the mean pain interference with sleep score evaluated on an 11-point NRS at the end of the Treatment Phase (Week 7 of the Treatment Phase) compared to Baseline (Week -1)
4. Number of days with intake of rescue medication, cumulative dose, and relative cumulative dose of rescue medication
5. Percentage of patients by category (‘Improved’, ‘Not improved’) of global assessment of symptoms evaluated on the patient global impression of change (PGIC) with a 7-point Likert scale at Visit 4
6. Occurrence of treatment-emergent adverse events (TEAEs)/treatment-emergent serious adverse events (TESAEs)
7. Percentage of patients by categorybased on the satisfaction of the patient with tolerability at Visit 4 on a 5-point Likert scale
8. Occurrence of addictive behavior based on the Addiction Behaviors Checklist (ABC) at Visit 3, 4, and 5
9. Occurrence of symptoms of abrupt drug withdrawal based on the Study Medication Withdrawal Questionnaire Version 2 (SMWQ V2) during the Wash-out Phase

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 11

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vertanical GmbH

Sponsor organisation

Vertanical GmbH

Address

Am Haag 14, Lochham Lochham

City

Gräfelfing

Postcode

82166

Country

Germany

Scientific contact point

Organisation

Vertanical GmbH

Contact name

Regulatory Affairs

Public contact point

Organisation

Vertanical GmbH

Contact name

Regulatory Affairs

Third parties 24

Locations

4 EU/EEA countries · 103 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 93 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

15 submissions — initial application plus substantial / non-substantial modifications