Phase III Randomized Controlled Trial Evaluating Efficacy and Safety of Capsaicin Cutaneous Patch in Post-Surgical Neuropathic Pain Patients
- Trial ID
- 2024-514934-19-00
- Protocol
- AV001
- Sponsor
- Averitas Pharma Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to demonstrate the **superiority** of Qutenza over a low-dose capsaicin control in reducing the 24-hour average pain intensity from baseline to Week 12 in subjects with post-surgical neuropathic pain (PSNP). This is clinically relevant as it aims to establish Qutenza as a more effective treatment option for managing pain in patients suffering from PSNP, potentially improving their quality of life and functional outcomes.
Secondary objectives include:
- Demonstrating the superiority of Qutenza over low-dose capsaicin control in reducing the treatment area size from baseline to Week 12 in subjects with PSNP.
- Assessing the safety and tolerability of Qutenza in subjects with PSNP.
- Confirming the long-term efficacy of Qutenza in subjects with PSNP.
- Assessing the long-term safety and tolerability of Qutenza in subjects with PSNP.
Participants
The clinical trial involves a total of **306 participants** who are experiencing **post-surgical neuropathic pain**. The study population includes both male and female subjects aged 18 years or older. Participants were selected based on their documented diagnosis of probable or definite post-surgical neuropathic pain, with a history of pain lasting between 6 to 60 months. The trial includes individuals who are either not currently receiving treatment for their condition or are on a stable systemic treatment that began more than 30 days prior to the trial's randomization visit. Participants are required to have moderate to severe pain, with a baseline 24-hour average pain intensity of at least 4 points on the Numeric Pain Rating Scale. The trial population is characterized by a willingness to adhere to restricted use of concomitant treatments and must have intact, dry, and non-irritated skin in the area where the investigational medicinal product will be applied. The study includes a vulnerable population, and both genders are represented. Participants' lifestyle considerations, such as diet and physical activity, are not specified in the available data.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, controlled, parallel-group, multi-site study to evaluate the efficacy and safety of Qutenza in subjects with **post-surgical neuropathic pain**. The trial aims to demonstrate the superiority of Qutenza over low-dose capsaicin control in changing the 24-hour average pain intensity from baseline to Week 12. The trial is expected to run from November 16, 2021, to August 30, 2025, with a maximum treatment period of 42 days for each participant.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, such as age, pain history, and skin condition. Following successful screening, participants will proceed to the randomization visit, where they will be assigned to either the Qutenza or control group. Subsequent follow-up visits will occur at regular intervals to monitor pain intensity, treatment area size, and any treatment-emergent adverse events (TEAEs). The primary endpoint is the change in 24-hour average pain intensity from baseline to the average score between Week 2 and Week 12. Secondary endpoints include changes in treatment area size and the incidence of TEAEs.
The expected length of participant involvement is up to 42 days, with conditions for early termination including significant adverse events or non-compliance with study protocols. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted to evaluate the overall efficacy and safety of the treatment. Participants are required to adhere to restricted use of concomitant treatments throughout the study duration.
Treatment
The clinical trial involves the use of **Qutenza 179 mg cutaneous patch** as the experimental medication. This product is a **cutaneous patch** containing the active substance **capsaicin**, with a pharmaceutical form designed for **cutaneous use**. The maximum daily dose of Qutenza is 11.93 mg, with a total maximum dose of 716 mg over a treatment period of up to 42 days. The patch is applied directly to the skin, and the administration is monitored to ensure compliance with the dosing schedule. The product is manufactured by GRÜNENTHAL GMBH and is authorized for use in the European Union under the marketing authorization number EU/1/09/524/001.
The comparator treatment in this study is a low-dose **capsaicin** cutaneous patch, also produced by GRÜNENTHAL GMBH. This patch is similarly designed for **cutaneous use** and contains the same active substance, **capsaicin**, but at a significantly lower maximum daily dose of 0.06 mg and a total maximum dose of 3.6 mg over the same 42-day treatment period. The low-dose patch serves as a control to evaluate the efficacy and safety of the higher-dose Qutenza patch in subjects with post-surgical neuropathic pain. Compliance with the administration of the comparator patch is also monitored throughout the trial.
Efficacy
The efficacy of the clinical trial evaluating Qutenza® in subjects with post-surgical neuropathic pain will be assessed using specific primary and secondary endpoints. The primary endpoint is the change from baseline to the average score of the entire period between Week 2 and Week 12 in the 24-hour average pain intensity. This will be measured using a validated pain intensity scale, ensuring accurate and reliable data collection.
Secondary endpoints include the change from baseline to Week 12 in the treatment area size, the incidence of treatment-emergent adverse events (TEAEs), and the incidence of TEAEs leading to discontinuation in the Core Phase. Additionally, the trial will assess changes from baseline to the weekly average score of Week 42 in the 24-hour average pain intensity, changes in treatment area size at Week 42, and the average score of the entire period between Week 2 and Week 42 in the 24-hour average pain intensity. The incidence of TEAEs and those leading to discontinuation in the Extension Phase will also be evaluated.
Data collection will occur at specified timepoints, including baseline, Week 2, Week 12, and Week 42, using electronic diaries for pain intensity ratings. The analysis will focus on demonstrating the superiority of Qutenza over low-dose **capsaicin** control, with the primary objective being a significant reduction in pain intensity from baseline to Week 12. The trial is designed to provide robust evidence of efficacy through comprehensive and systematic assessment of these endpoints.
Inclusion and Exclusion Criteria
Inclusion Criteria
- The subject has given written informed consent to participate.
- Female or male subjects aged 18 years or older.
- For women of childbearing potential: negative pregnancy tests at Screening Visit (Visit 1), the Randomization Visit (Visit 2), and prior to each reapplication of the IMP, and must have agreed to practice medically acceptable methods of birth control.
- Documented diagnosis of PSNP by the following criteria: a. A history of post-surgical pain with a duration of at least 6 months to maximally 60 months that is plausibly related to the surgical intervention as documented on a body map. b. DN4i of at least 3 out of 7 points at Visit 1. c. The pain must extend beyond the scar area to neuroanatomically adjacent skin areas and be related to the site of the surgery.
- Documented diagnosis of probable or definite PSNP according to the following criteria: a. The pain must be associated with sensory signs in the same neuroanatomically plausible distribution. The area of sensory changes may extend beyond, be within, or overlap with the area of pain (criterion for probable neuropathic pain), or b. In addition to 5a: Direct surgical evidence (e.g., surgeon´s clear verification of an intraoperative nerve lesion) (criterion for definite neuropathic pain).
- The subject has moderate to severe pain with a baseline value for 24- hr average pain intensity of at least 4 points on the NPRS. The baseline value is calculated as the average of the 24-hr average pain intensity ratings of the Baseline Phase (Day -7 to Day -1). At least 5 (out of the last 7 days) pain ratings should be available during the Baseline Phase. If less than 5 pain ratings are available in the last 7 days, the subject may be rescheduled for Visit 2 (1 time only) after having received appropriate re-training in the use of the e-diary to ensure compliance.
- The size of the affected painful intact skin area is not larger than the size of 4 standard Qutenza topical systems (1120 cm2).
- The skin in the area where the IMP will be applied, and that may also contain the scar tissue, is intact, dry, and non-irritated (i.e., there are no signs and symptoms of skin disease, skin irritation, inflammation or injury, such as active herpes zoster lesions, atopic dermatitis, ulceration, wounds). This is reflected by a dermal assessment score of 0 = "no evidence of irritation" or 1 = "minimal erythema, barely perceptible".
- The subject is willing to adhere to the restricted use of concomitant treatments (see concomitant treatments in Section 1.4.2).
- The subject experiencing pain is: a. currently not receiving treatment for PSNP or b. receives a stable systemic treatment for PSNP that started more than 30 days prior to the Randomization Visit (Visit 2).
Exclusion Criteria
- The subject received Qutenza before the Randomization Visit (Visit 2) or received a medical device in another clinical trial within 7 days before the Randomization Visit (Visit 2), or a. Any former use of topical capsaicin in the area of the PSNP before Visit 2, except for the use of a low-dose (<1%) capsaicin product – but not within 7 days before Visit 2. b. The subject participated previously in this clinical trial or participated in another clinical trial for the treatment of PSNP completing less than 3 months ago.
- A score of 0 out of 5 in all 3 categories of the neurological/sensory examinations, i.e., for warm sensation, pinprick and cold sensation at the Screening Visit (Visit 1).
- The subject reported a 24-hr average pain intensity score of 10 on the NPRS for at least 4 days during the Baseline Phase.
- Any painful procedure planned during the course of the trial that may, in the opinion of the investigator, affect the efficacy or safety assessments.
- Subjects with PSNP related to a surgery/condition with a high potential for confounding symptoms, e.g., the pain is at least partially due to pain in deeper structures such as muscles or bones (including referred pain from deeper structures) as listed in examples in Protocol Table 2.
- Other painful conditions in the body area that is affected by PSNP and may affect efficacy or safety assessments and cannot be discriminated from the target pain by the subject, including infectious, non-infectious, inflammatory or neuropathic conditions which could also be complications related to the previous surgical procedure.
- Neuropathic pain areas located only on the face, above the hairline of the scalp, and/or in proximity to mucous membranes.
- Hypersensitivity to capsaicin (i.e., chili peppers or over-the-counter [OTC] capsaicin products), or to any excipients of the IMP or to excipients of the cleansing gel in use and their components, or to topical anesthetics in use and their components.
- Pending litigation due to chronic pain or disability.
- The subject has a history of alcohol or drug abuse or is actively abusing drugs (including alcohol, medication) during the 1 year prior to the Screening Visit (Visit 1) as judged by the investigator.
- Evidence or history of severe psychiatric illness/disorder during the 3 years prior to the Screening Visit (Visit 1) that, in the investigator's opinion, may affect efficacy or safety assessments or may compromise the subject's safety during trial participation, e.g., major depression, major anxiety disorder, psychosis, severe personality disorders.
- Evidence of cognitive impairment including dementia that may interfere with the subject's ability to complete pain assessments requiring recall of the average pain level in the past 24 hrs.
- Surgical intervention in the last 3 months preceding the Screening Visit (Visit 1) if it is affecting the efficacy or safety assessments, or any scheduled or planned surgery during the trial, with the exception of the Extension Phase if the planned surgery is not expected to affect the efficacy or safety assessments.
- Patients with current clinically significant disease(s) or condition(s) (including clinically significant cardiovascular disease and/or significant pain in other areas) that may affect efficacy or safety assessments, or any other reason which, in the investigator's opinion, may preclude the subject's participation in the full duration of the trial. Patients with current signs and symptoms consistent with Coronavirus disease 2019 (COVID-19) (e.g., dry cough, dyspnea, sore throat, fatigue, fever) or subjects who had those symptoms within the last 14 days prior to screening and had a positive SARS-CoV2 PCR test result.
- Unstable or poorly controlled blood pressure which, in the opinion of the investigator, would put the subject at risk of severe adverse blood pressure increases upon IMP application.
- Known or suspected of not being able to comply with the requirements of the trial protocol or the instructions of the trial site staff.
- Not able to communicate meaningfully with the trial site staff.
- The subject is an employee of the investigator or trial site, with direct involvement in the proposed trial or other trials under the direction of that investigator or trial site, or is a family member of the employees or the investigator.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 16 Nov 2021 | 58 |
 The Netherlands | Not Recruiting | 16 Nov 2021 | — |
 Poland | Not Recruiting | 16 Nov 2021 | 45 |
 Spain | Not Recruiting | 16 Nov 2021 | 75 |
| Netherlands | — | — | 26 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Qutenza 179 mg cutaneous patch | Test | CUTANEOUS PATCH | CUTANEOUS USE | 11.93 | 42 | PRD4980580 |
CAPSAICIN | Comparator | CUTANEOUS PATCH | CUTANEOUS USE | 0.06 | 42 | PRD8903578 |
Qutenza 179 mg cutaneous patch | Test | CUTANEOUS PATCH | CUTANEOUS USE | 11.93 | 42 | PRD4980581 |