Primary objective:To demonstrate superiority of Qutenza over low-dose capsaicin control in change from baseline to Week 12 in the 24-hr average pain intensity in subjects with PSNP.Secondary objective:• To demonstrate superiority of Qutenza over low…
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Post-surgical neuropathic pain (PSNP)
Research involving
Sponsors and support
Intervention
No registrations found.
Outcome measures
Primary outcome
Primary End Point:
• For the US: Change from baseline to the weekly average score of Week 12 in
the 24-hr average pain intensity.
• For non-US countries/regions: Change from baseline to the average score of
the entire period between Week 2 and Week 12 in the 24-hr average pain
intensity.
Secondary outcome
Secondary End Point:
• Change from baseline to Week 12 in the treatment area size.
• Incidence of treatment-emergent adverse events (TEAEs).
• Incidence of TEAEs leading to discontinuation in the Core Phase.
• Change from baseline to the weekly average score of Week 42 in the 24-hr
average pain intensity.
• Change from baseline to Week 42 in the treatment area size.
• Change from baseline to the average score of the entire period between Week 2
and Week 42 in the 24-hr average pain intensity.
• Incidence of TEAEs.
• Incidence of TEAEs leading to discontinuation in the Extension Phase.
Background summary
Introduction:
Chronic post-surgical pain is a problem worldwide. It is often overlooked or
minimized, poorly treated (Schug et al. 2019), causes disability, and is
associated with reduced quality of life and increased use of health care
resources (Lavand*homme 2017b). Given that 312 million major surgeries are
performed annually worldwide, the magnitude of the problem becomes obvious
(Katz et al. 2019), and despite advances in surgical techniques the prevalence
of chronic post-surgical pain is still high (Lavand*homme 2017b). Chronic
post-surgical pain has become a health priority and has been included in the
upcoming version of the International Classification of Disease, ICD-11 (Schug
et al. 2019). Certain frequently performed surgical procedures have inherent
risks of developing chronic post-surgical pain. These operations often involve
damage to large peripheral nerves (Kehlet et al. 2006, Durkin et al. 2010).
Neuropathic features occur in approximately 35% to
57% of patients with chronic post-surgical pain (Lavand*homme 2017a), a
prevalence that varies according to the type of operation, e.g.,
post-thoracotomy (29%), post-mastectomy (31%), cesarean section (21.4%),
saphenectomy (15.7%), inguinal hernia repair (11.4%), cholecystectomy (6.1%)
(Dualé et al. 2011, Haroutiunian et al. 2013, Pickering et al. 2017).
PNP such as PSNP presents in a defined localized area of the body, with an area
of pain usually related to the primary lesion. It is a type of neuropathic pain
that is characterized by a temporal relationship to a known nerve injury
(Freeman et al. 2019).
PSNP has consistent and circumscribed area(s) of maximum pain, associated with
negative or positive signs of sensory disturbance in the innervation of the
injured nerve, and/or spontaneous symptoms characteristic of neuropathic pain
(Freeman et al. 2019, Mick et al. 2012).
Background to the IMP:
Capsaicin is a highly selective agonist of transient receptor potential
vanilloid-1 (TRPV-1). The
TRPV-1 receptor is an ion channel-receptor complex expressed on small-diameter
sensory neurons (C- and Aδ-fibers), e.g., nociceptors in the skin which are
specialized in the detection of painful or noxious stimuli. Qutenza is an
adhesive capsaicin dermal topical system that delivers a high concentration of
synthetic capsaicin directly to the site of pain, where it induces reversible
dermo-epidermal denervation and depletion of capsaicin-sensitive nociceptors
(Lo Vecchio et al. 2018), and enables the effective treatment of PNP
conditions.
Study objective
Primary objective:
To demonstrate superiority of Qutenza over low-dose capsaicin control in change
from baseline to Week 12 in the 24-hr average pain intensity in subjects with
PSNP.
Secondary objective:
• To demonstrate superiority of Qutenza over low-dose capsaicin control in
change from baseline to Week 12 in treatment area size in subjects with PSNP.
• To assess the safety and tolerability of Qutenza in subjects with PSNP.
• To confirm the long-term efficacy of Qutenza in subjects with PSNP.
• To assess the long-term safety and tolerability of Qutenza in subjects with
PSNP.
Study design
This is an interventional, Phase III, double-blind, randomized, controlled,
parallel-group, multi-site, clinical trial to confirm the efficacy and safety
of repeated topical application of Qutenza (capsaicin 8% topical system) versus
low-dose capsaicin control (capsaicin 0.04% topical system) in subjects with
moderate to severe PSNP. After a Screening Period of up to 19 days, including
the Baseline Phase from Day -7 to Day -1, subjects will be allocated to Qutenza
or to low-dose capsaicin control topical system (capsaicin 0.04%) at the
Randomization Visit. The blinded Treatment Period consists of a Core Phase (Day
1 to Week 12) and an Extension Phase (Week 13 to Week 42), which includes a
Follow- up of 14 days. Each subject is expected to be in the trial for up to 44
weeks.
Intervention
Subjects who fulfil all inclusion criteria and do not meet any of the exclusion
criteria will be randomly assigned to 1 of the 2 treatments in a 1:1 ratio:
• Qutenza (capsaicin 8% topical system, containing capsaicin 179 mg or
capsaicin 640 µg/cm2 of topical system).
• Low-dose capsaicin control (capsaicin 0.04% topical system, containing
capsaicin 0.9 mg or capsaicin 3.2 µg/cm2 of topical system).
The appearance of Qutenza and low-dose control topical systems will not be
distinguishable. The size of each IMP topical system is 14 cm by 20 cm (280
cm2). Up to 4 topical systems (1120 cm2), depending on the size of the painful
affected area, will be applied topically for 60 mins to the treatment area.
Prior to the IMP application, the treatment area will be pre-treated with a
topical anesthetic.
The initial IMP application will occur at the Randomization Visit (Visit 2/Day
1).
Re-application of the IMP is dependent on: the investigator*s judgment that the
subject*s pain level is appropriate (e.g., pain levels >4 during the last week
preceding the re-application), and the subject*s wish to receive another
treatment based on their pain assessment. Re-application is not allowed if the
subject did not tolerate previous IMP application(s) as judged by the
investigator, developed hypersensitivity to the IMP, or if the subject is
pregnant.
The first re-application of the IMP can take place at the earliest 12 weeks
after the first application (i.e., at Visit 6, after the Core Phase of the
Treatment Period). During the Extension Phase of the trial, the minimum time
interval between applications should be 8 weeks. The last IMP application can
occur no later than 40 weeks after the first IMP application (if an application
occurs at Week 40, the Final Visit has to take place at the earliest 14 days
later).
Study burden and risks
Please refer to section 6. *What side effects could you experience?* and
section 7. *What are the pros and cons if you take part in the study?* in the
Subject Information For Participation In Medical Research Form for an overview
of the risks and side effects.
Mount Kemble Avenue 360
Morristown, NJ 07960
US
Mount Kemble Avenue 360
Morristown, NJ 07960
US
Listed location countries
Age
Inclusion criteria
General
1. The subject has given written informed consent to participate.
2. Female or male subjects aged 18 years or older.
3. 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.
Confirmation of diagnosis of chronic moderate to severe PSNP (see also Protocol
Table 1)
4. 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.
5. 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).
6. 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.
Suitability for treatment with IMP
7. The size of the affected painful intact skin area is not larger than the
size of 4 standard Qutenza topical systems (1120 cm2).
8. 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".
Eligibility with regard to protocol adherence, to allowed pre-treatments and
concomitant treatments
9. The subject is willing to adhere to the restricted use of concomitant
treatments (see concomitant treatments in Section 1.4.2).
10. 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
General or previous treatments 1. 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. 2. 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). Confounding factors 3. The subject
reported a 24-hr average pain intensity score of 10 on the NPRS for at least 4
days during the Baseline Phase. 4. Any painful procedure planned during the
course of the trial that may, in the opinion of the investigator, affect the
efficacy or safety assessments. 5. 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. 6. 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. Contraindications to
IMP 7. Neuropathic pain areas located only on the face, above the hairline of
the scalp, and/or in proximity to mucous membranes. 8. 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.
Medical history/concurrent condition(s)/other factors 9. Pending litigation due
to chronic pain or disability. 10. 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. 11.
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. 12. 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.
13. 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. 14. 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. 15. 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. 16.
Known or suspected of not being able to comply with the requirements of the
trial protocol or the instructions of the trial site staff. 17. Not able to
communicate meaningfully with the trial site staff. 18. 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | EUCTR2021-001409-64-NL |
CCMO | NL77643.056.21 |
Other | WHO Universal Trial Number (UTN): U1111-1272-1340 |