Comparison of Qutenza (8% Capsaicin) With a Low-dose Capsaicin for Treatment of Nerve Pain After Surgery

• Sponsor: Averitas Pharma, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04967664
• Collaborator: (none)
• Enrollment: 408
• Locations: 65
• Arms: 2
• Anticipated Duration (Months): 32.6
• Patients Per Site: 6.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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 postsurgical neuropathic pain (PSNP).

Condition or Disease	Intervention/Treatment	Phase
Post Surgical Neuropathic Pain	Drug: Qutenza (capsaicin) 8% topical system; Drug: capsaicin 0.04% topical system	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 408 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An Interventional, Phase III, Double-blind, Randomized, Controlled, Parallel-group, Multi-site, Clinical Trial Evaluating the Efficacy and Safety of Qutenza® in Subjects With Post-surgical Neuropathic Pain
• Actual Study Start Date: Jul 13, 2021
• Anticipated Primary Completion Date: Nov 1, 2023
• Anticipated Study Completion Date: Apr 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Qutenza (capsaicin) 8% topical system Qutenza (capsaicin 8% topical system, containing capsaicin 179 mg or capsaicin 640 µg/cm2 of topical system)	Drug: Qutenza (capsaicin) 8% topical system; High concentration capsaicin
Active Comparator: Low-dose capsaicin control capsaicin 0.04% topical system	Drug: capsaicin 0.04% topical system; Low-dose capsaicin control

Outcome Measures

Primary Outcome Measures

1. Change from baseline to the weekly average score of Week 12 in the 24-hr average pain intensity. [From the Baseline Phase (Day -7 to Day -1) to Visit 6 (Week 12/Day 84).]

   The 24-hr average pain intensity will be assessed and reported in the electronic diary (e-diary) once daily in the evening, using an 11-point numeric pain rating scale (NPRS, from 0 = no pain to 10 = pain as bad as you can imagine).

Secondary Outcome Measures

1. Change from baseline to the weekly average score of Week 42 in the 24-hr average pain intensity. [Baseline Phase (Day -7 to Day -1) to Final Visit (Week 42/Day 294).]

   The 24-hr average pain intensity will be assessed and reported in the e-diary once daily in the evening using an 11-point NPRS (from 0 = no pain to 10 = pain as bad as you can imagine).

2. Change from baseline to the average score of the entire period between Week 2 and Week 42 in the 24-hr average pain intensity. [Baseline Phase (Day -7 to Day -1) to the Final Visit (Week 42/Day 294).]

   The 24-hr average pain intensity will be assessed and reported in the e-diary once daily in the evening, using an 11-point NPRS (from 0 = no pain to 10 = pain as bad as you can imagine).

3. Incidence of Treatment-Emergent Adverse Events (TEAEs) (Safety and tolerability) [Day 1 to Final Visit (Week 42/Day 294).]

   Documentation of TEAEs

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 investigational medicinal product (IMP), and must have agreed to practice medically acceptable methods of birth control.

Confirmation of diagnosis of chronic moderate to severe PSNP

1. Documented diagnosis of PSNP by the following criteria:

2. 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.

3. Douleur Neuropathique 4 interview (DN4i) of at least 3 out of 7 points at Visit

5. The pain must extend beyond the scar area to neuroanatomically adjacent skin areas and be related to the site of the surgery.

6. Documented diagnosis of probable or definite PSNP according to the following criteria (Finnerup et al. 2016):

7. 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

8. In addition to 5a : Direct surgical evidence (e.g., surgeon´s clear verification of an intraoperative nerve lesion) (criterion for definite neuropathic pain).

9. 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

1. The size of the affected painful intact skin area is not larger than the size of 4 standard Qutenza topical systems (1120 cm2).

2. 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

1. The subject is willing to adhere to the restricted use of concomitant treatments .

2. The subject experiencing pain is:

3. currently not receiving treatment for PSNP or

4. receives a stable systemic treatment for PSNP that started more than 30 days prior to the Randomization Visit (Visit 2).

Non-exhaustive list of examples of types of surgeries with resulting PSNP:

Thoracic surgery Breast surgery Abdominal surgery (cholecystectomy, appendectomy) Donor nephrectomy Gynecologic surgery (hysterectomy, C-section) Varicose vein surgery Inguinal herniotomy Lipoma removal Knee surgery Knee arthroplasty Ankle surgery

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

2. 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.

3. 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.

4. 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

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.

2. Any painful procedure planned during the course of the trial that may, in the opinion of the investigator, affect the efficacy or safety assessments.

3. 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.

4. 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.

Non-exhaustive list of examples of types of surgeries/conditions not suitable for eligibility Any surgery performed due to suspected neoplasia: suspected residual neoplasia or metastases Conditions where nociceptive or neuropathic pain has been the reason for the surgery, e.g., failed back surgery, carpal tunnel syndrome or other nerve compression syndromes leading to neuropathic pain, (e.g., meralgia paresthetica) Conditions of projected neuropathic pain (i.e., from inguinal hernia repair) with painful symptoms in the genital region, e.g., the scrotum or vagina Amputations Radicular pain and nerve trunk lesions Scar pain neuroma Complex Regional Pain Syndrome (Type I or Type II)

Contraindications to IMP

1. Neuropathic pain areas located only on the face, above the hairline of the scalp, and/or in proximity to mucous membranes.

2. 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

1. Pending litigation due to chronic pain or disability.

2. 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.

1. 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.

2. 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.

3. 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.

4. 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 patients who had those symptoms within the last 14 days prior to screening and had a positive SARS-CoV2 PCR test result.

5. 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.

6. Known or suspected of not being able to comply with the requirements of the trial protocol or the instructions of the trial site staff.

7. Not able to communicate meaningfully with the trial site staff.

8. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tucson Orthopaedic Institute	Tucson	Arizona	United States	85712
2	UCSD Center for Pain Medicine	La Jolla	California	United States	92037
3	ILD Research Center	Vista	California	United States	92009
4	International Spine, Pain, and Performance Center	Washington	District of Columbia	United States	20006
5	Synergy Healthcare	Bradenton	Florida	United States	33705
6	South Lake Pain Institute	Clermont	Florida	United States	34711
7	University Clinical Research - DeLand Clinical Research Unit	DeLand	Florida	United States	32720
8	Universal Axon Clinical Research	Doral	Florida	United States	33166
9	Clinical Research of West Florida	Tampa	Florida	United States	33606
10	Drug Studies America	Marietta	Georgia	United States	30060
11	Injury Care Research	Boise	Idaho	United States	83713
12	Millennium Pain Center	Bloomington	Illinois	United States	61704
13	Rush University Medical Center	Chicago	Illinois	United States	60612
14	The University of Chicago Medicine	Chicago	Illinois	United States	60637
15	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
16	Neuroscience Research Center, LLC	Overland Park	Kansas	United States	66210
17	Kansas City Bone & Joint Clinic, P.A.	Overland Park	Kansas	United States	66211
18	Boston Clinical Trials	Boston	Massachusetts	United States	02131
19	Great Lakes Research Group, Inc.	Bay City	Michigan	United States	48706
20	Premier Pain Centers	Shrewsbury	New Jersey	United States	07702
21	Albuquerque Neuroscience, Incorporated	Albuquerque	New Mexico	United States	87109
22	Montefiore Medical Center	Bronx	New York	United States	10467
23	University of Rochester Medical Center (URMC)	Rochester	New York	United States	14618
24	META Medical Research Institute, LLC	Dayton	Ohio	United States	45432
25	New Phase Research & Development	Knoxville	Tennessee	United States	37909
26	HD Research LLC	Bellaire	Texas	United States	77401
27	Cedar Health Research, LLC	Dallas	Texas	United States	75251
28	Expert Pain	Houston	Texas	United States	77079
29	Sweedish Pain Clinic	Seattle	Washington	United States	98122
30	Centre Hospitalier Departemental Vendee - Centre d'evaluation et de Traitement de la Douleur	La-Roche-Sur-Yon	Pays De La Loire	France
31	CHU de Nantes - Hopital Nord Laennec	Nantes	Pays De La Loire	France
32	CHU Amiens Picardie	Amiens		France
33	Centre Hospitalier Jean Rougier	Cahors		France
34	Clinique Francois Chenieux	Limoges		France
35	Groupe Hospitalier Paris saint-Joseph	Paris Cedex 14		France
36	Cochin Hospital-Paris Descartes University	Paris		France
37	CHU Poitiers / La Miletrie	Poitiers		France
38	NOCEPTA	Hengelo		Netherlands
39	Leiden University Medical Center (LUMC)	Leiden		Netherlands
40	Maxima Medisch Centrum Veldhoven	Veldhoven		Netherlands
41	Centrum Medyczne Pratia Katowice	Katowice	Silesia	Poland
42	Silmedic Sp z o.o. Oddzial w Katowicach	Katowice	Silesia	Poland
43	Vitamed Nzoz Im. Edyty Jakubow	Białystok		Poland
44	Nzoz Neuro-Medic	Katowice		Poland
45	Linden Centrum Medyczne	Krakow		Poland
46	Instytut Zdrowia dr Boczarska-Jedynak	Oświęcim		Poland
47	Lubelskie Centrum Diagnostyczne	Swidnik		Poland
48	Centrum Badan Medycznych Nigrir	Warszawa		Poland
49	FutureMeds sp. z o. o.	Wroclaw		Poland
50	Hospital General Universitario de Alicante	Alicante		Spain
51	Hospital Clinic i Provincial de Barcelona	Barcelona		Spain
52	Hospital Del Mar	Barcelona		Spain
53	Hospital Universitario de Bellvitge	L'Hospitalet De Llobregat		Spain
54	Hospital Universitario de La Princesa	Madrid		Spain
55	Hospital Universitario La Moraleja	Madrid		Spain
56	Clinica Universidad de Navarra	Pamplona		Spain
57	Clinica Gaias	Santiago de Compostela		Spain
58	Hospital Clinico Universitario de Valencia	Valencia		Spain
59	Hospital Clinico Universitario de Valladolid	Valladolid		Spain
60	Accellacare - (MeDiNova Limited) - Northamptonshire	Corby	Northamptonshire	United Kingdom
61	Accellacare - (MeDiNova Limited) - Yorkshire	Shipley	Yorkshire	United Kingdom
62	Aberdeen Royal Infirmary (ARI) - NHS Grampian	Aberdeen		United Kingdom
63	Accellacare	Coventry		United Kingdom
64	Accellacare - (MeDiNova Limited) - North London	Northwood		United Kingdom
65	MeDiNova South London Quality Research Site	Sidcup		United Kingdom

Sponsors and Collaborators

• Averitas Pharma, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Averitas Pharma, Inc.
• ClinicalTrials.gov Identifier: NCT04967664
• Other Study ID Numbers: AV001
• First Posted: Jul 19, 2021
• Last Update Posted: Aug 9, 2022
• Last Verified: Aug 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neuralgia; Capsaicin

Study Results

No Results Posted as of Aug 9, 2022