Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Central Neuropathy of Any Genesis

Sponsor

Apurano Pharmaceuticals GmbH (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06071949

Collaborator

(none)

558

Enrollment

Arms

14.6

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Over the last years a rising medical need for treatment of chronic pain was identified. Based on previous findings indicating the pain modulating effects of cannabinoids in chronic pain disorders, this clinical trial investigates the efficacy and tolerability of the THC-focused nano endocannabinoid system modulator AP707 in patients with chronic pain disorders due to central neuropathy of any genesis. Patients receive AP707 or placebo over the course of 14 weeks as an add-on to the standard of care. Changes in pain intensity, quality of life and sleep and others measures are monitored through different scales to assess the efficacy of AP707 in patients with chronic pain due to central neuropathy of any genesis.

Condition or Disease	Intervention/Treatment	Phase
Pain Pain Syndrome Pain, Chronic Chronic Pain Chronic Pain Syndrome Neuropathic Pain Central Neuropathic Pain Paraplegia Multiple Sclerosis Stroke Phantom Limb Syndrome With Pain Phantom Pain Traumatic Brain Injury	Drug: Adezunap Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

558 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Central Neuropathy of Any Genesis

Anticipated Study Start Date :

Oct 15, 2023

Anticipated Primary Completion Date :

Sep 30, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment group Sublingual spray with maximum application of 16 actuations per day or a maximum daily dose of 17,6mg THC distributed over 4 daily intakes.	Drug: Adezunap Sublingual spray with maximum application of 16 actuations per day or a maximum daily dose of 17,6mg THC distributed over 4 daily intakes.
Experimental: Control group Sublingual spray with maximum application of 16 actuations per day distributed over 4 daily intakes.	Drug: Placebo Sublingual spray with maximum application of 16 actuations per day distributed over 4 daily intakes.

Arm

Intervention/Treatment

Experimental: Treatment group

Sublingual spray with maximum application of 16 actuations per day or a maximum daily dose of 17,6mg THC distributed over 4 daily intakes.

Drug: Adezunap

Sublingual spray with maximum application of 16 actuations per day or a maximum daily dose of 17,6mg THC distributed over 4 daily intakes.

Experimental: Control group

Sublingual spray with maximum application of 16 actuations per day distributed over 4 daily intakes.

Drug: Placebo

Sublingual spray with maximum application of 16 actuations per day distributed over 4 daily intakes.

Outcome Measures

Primary Outcome Measures

Change in pain level on the Numeric Rating Scale (NRS, 0-10) between baseline and at treatment week 14 (end of first treatment phase) in comparison of study arm 1 (verum) and study arm 2 (placebo) [Once daily in week 4 and 14]

Secondary Outcome Measures

Change in the pain score of the Neuropathic Pain Symptom Inventory (NPSI) questionnaire between baseline and at treatment week 14 in comparison of study arm 1 (verum) and study arm 2 (placebo) [Week 1 and 14]
Change in pain level on the Numeric Rating Scale (0-10) between baseline and in treatment week 5 and 11 in comparison of study arm 1 (verum) and study arm 2 (placebo) [Several times weekly in week 4, 5 and 11]
Responder analysis for endpoints 1) for treatment week 14 [Week 14]
Proportion of patients who experienced > 30 % improvement in pain score (Numeric Rating Scale) Proportion of patients who experienced > 40 % improvement in pain score (Numeric Rating Scale) Proportion of patients who experienced > 50 % improvement in pain score (Numeric Rating Scale)
Change in sCPT (percentage of change in dosage and percentage of change in combination of analgesic measures) in both study arms from start to week 14 [Week 14]
Change in psychological distress using Depression Anxiety Stress Scales Short Form (DASS-21) questionnaire from start to week 14 [Week 1 and 14]
Change of Patient Global Impression of Change (PGIC) from start to week 14 [Week 14]
Change in quality of life using the Veterans RAND (VR-12) questionnaire from start to week 14 [Week 1 and 14]
Change in sleep quality using the Regensburg Insomnia Scale (RIS) from start to week 14 [Week 1 and 14]
Change in pain score of the Brief Pain Inventory - Short Form (BPI-SF) questionnaire from start to week 14 [Week 1 and 14]
Area under NRS-curve until treatment week 5, 11 and 14 [Week 5, 11 and 14]
Change in VR-12 components (physical component summary PCS, mental component summary MCS) from start to week 14 [Week 1 and 14]
Number of patients with rescue medication over the course of the clinical trial and within periods: until treatment week ≤5, ≤11 and ≤14 [Week 5, 11 and 14]

Other Outcome Measures

Number and severity of adverse events (AE) [Week 5, 11 and 14]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed and dated informed consent form
Patients with chronic pain due to central neuropathy of any genesis since at least 3 months
Female and male patients (> 18 years)
Patients with more than 1 year life expectancy
Patients with optimized sCPT on study entry as defined in section 3.1.1 and section 3.1.3 of the study protocol
Willingness of study patients of both sexes to use reliable contraception during study participation and for three months after taking the last study medication
Good command of German language, in order to understand questionnaires in German
Current moderate to severe pain with pain intensity > 5 on Numeric Rating Scale (NRS, 0 - 10) and thus an existing need for further pain therapy
Completed QUISS (Quantification Inventory for Somatoform Syndromes) questionnaire with 45 or less score points

Exclusion Criteria:

Medical history of hypersensitivity or intolerance to the investigational product or its ingredients or to ingredients of similar chemical structure
Known intolerance to cannabinoids or cannabis products.
Participation in another clinical trial within the last four weeks prior to inclusion.
Pregnant or nursing women (as excluded by pregnancy testing at visit 1).
Other medical conditions that do not allow the trial subject to appraise the nature, scope, and potential consequences of the clinical trial
Indications that the trial subject is unlikely to comply with the study protocol (e.g., unwillingness to cooperate)
Known use of medicinal cannabis products within the last 8 weeks
Active malignant tumor disease, tumor pain, or other dominant severe pain other than that of the study indication
Known history of severe liver or kidney diseases
Known history of severe cardiovascular disease
Known history of or acute mental illness such as severe depression, psychosis, bipolar disorder, mania, anxiety, or obsessive-compulsive disorder
Known history of addictive disease (e.g., alcohol, medication, drug addiction)
Answered during Screening less than 12 times of 18 the pain intensity (NRS) inquiry
Laboratory liver values: Alanine aminotransferase (ALT, GPT) > 3 x ULN (Upper Limit of Normal range), Aspartate aminotransferase (AST, GOT) > 3 x ULN, Alkaline phosphatase (AP) > 2.5 x ULN, and for bilirubin > 1.5 x ULN
Laboratory renal value: Serum creatinine > 1.5 ULN