Trial Title:
Efficacy and Safety of ATX01 in Adult Patients With CIPN (Chemotherapy-induced Peripheral Neuropathy)
NCT ID:
NCT05593614
Condition:
Chemotherapy-induced Peripheral Neuropathy
Conditions: Official terms:
Peripheral Nervous System Diseases
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Intervention:
Intervention type:
Drug
Intervention name:
ATX01 10%
Description:
A 100 mL bottle of hydrogel formulation containing 10% amitriptyline hydrochloride w/w
Arm group label:
ATX01 10%
Intervention type:
Drug
Intervention name:
ATX01 15%
Description:
A 100 mL bottle of hydrogel formulation containing 15% amitriptyline hydrochloride w/w
Arm group label:
ATX01 15%
Intervention type:
Drug
Intervention name:
Placebo
Description:
A 100 mL bottle of hydrogel formulation containing no active substance
Arm group label:
ATX01 Placebo
Summary:
The purpose of this clinical trial is to compare the efficacy of twice daily applications
of ATX01 (10% & 15%) versus placebo during a 12-week treatment period in treating
chemotherapy-induced peripheral neuropathy (CIPN) in adult cancer survivor patients.
Criteria for eligibility:
Criteria:
Inclusion criteria
1. Male or female patients of 18 years and older.
2. Patients having signed a written informed consent prior to any study-related
procedure.
3. Body mass index of 18 to 35 kg/m2 (inclusive).
4. With an estimated life expectancy ≥6 months at study entry.
5. Patients with painful sensory CIPN resulting from prior treatment of cancer with
taxanes or platins. A diagnosis of CIPN should be supported by i) onset of pain in
hands or feet after exposure to taxanes or platins, ii) presence of painful symptoms
in a symmetrical stocking and/or glove distribution, AND iii) painful symptoms may
be accompanied by nonpainful symptoms (eg, tingling/pins and needles intensity and
numbness intensity).
6. Patients who have stopped their chemotherapy treatment with taxanes or platins or
any other neurotoxic chemotherapy for ≥24 weeks at the time of the screening visit.
7. Patients with CIPN pain for ≥24 weeks at the time of the screening visit.
8. Patients with a mean value of pain intensity ≥4 and ≤9 in target study extremities
(left and right feet or left and right hands) on the 11 point NPRS at baseline. Non
target extremities can be treated regardless of the pain intensity.
9. Patients with symmetrical stocking or glove distribution pain, NPRS (≤1 point
difference) in the target study extremities at screening.
10. Neuropathic Pain (DN4) score ≥4 in the target study extremities (hands or feet) at
the screening visit
11. Treatment naïve patients or patients in whom any prior CIPN treatment (except oral
amitriptyline [AMT]) has not been modified during the 4 weeks preceding the
screening visit and is planned to be maintained at the same regimen during the
course of the study (prior treatment includes pharmacological and nonpharmacological
treatments).
12. Male patients should agree to use a condom along with another medically acceptable
contraceptive method, where applicable according to local guidelines, if he is
engaged in sexual activity with a woman of childbearing potential (WOCBP) from the
day of the signature of the informed consent and up to 90 days after the
End-of-Study (EoS) Visit. Male patients should agree not to donate sperm until 30
calendar days after the last dose of study drug.
13. Females must comply with the following in order to be enrolled:
1. WOCBP with negative serum pregnancy test results can be enrolled only if
willing to use an acceptable contraceptive method, ie, oral contraceptives,
patch contraceptives, injection contraceptives, implantable hormonal
contraceptives, male condom with intravaginal spermicide, diaphragm or cervical
cap with spermicide, vaginal contraceptive ring, intrauterine device or system,
surgical sterilization (hysterectomy, bilateral oophorectomy, and/or bilateral
salpingectomy), tubal ligation/occlusion, vasectomized partner, or sexual
abstinence, if this is the patient's current practice, from at least 14 days
prior to the screening visit and throughout the study and for at least 30 days
after the completion of the study.
2. Or surgically sterilized for at least 6 months.
3. Or menopausal for at least 1 year.
Exclusion criteria
1. Patients who are not compliant in completion of pain ratings during the screening
period. Patients having <5 of 7 records of average pain intensity in the target
study extremities from Day -7 to Day -1 will be excluded. If a patient misses
records of 2 days out of 7 days, the patient will be included in the study; however,
patients missing 3 or more days of records will be excluded from the study.
2. Clinical evidence of a preexisting painful peripheral neuropathy resulting from
another cause than chemotherapy, eg, diabetic neuropathy, posttraumatic neuropathy,
carpal/tarsal tunnel syndrome, radiculopathy, spinal stenosis, brachial plexopathy,
or other preexisting symptomatic neuropathy due to alcoholism, vitamin B deficiency,
hypothyroidism, human immunodeficiency virus. Patients may be included in the study,
providing that pain appeared after chemotherapy, while other non-painful symptoms
could have been present before start of chemotherapy.
3. Skin irritation, or lesions (eg open skin wounds, infections, inflammations, or
exfoliative dermatitis) of any type on the hands or feet (or only on the hands if
the study drug is not applied on the feet and vice versa [only on the feet if the
study drug is not applied on the hands]).
4. Presence of glaucoma.
5. Presence of urinary retention (or significant prostatic hypertrophy at risk of
urinary retention).
6. Angina or myocardial infarction in the year preceding screening visit.
7. History and/or presence of major depressive episode. Patients with a medical history
of bipolar disorder, alcohol abuse, or psychotic disorder are also excluded.
8. Patients who are at significant risk of suicide, or are a danger to self or others,
in the opinion of the investigator, based upon clinical interview and the C-SSRS at
screening and baseline. Affirmative answer to suicidal ideation questions 4 or 5
within the last 6 months and / or suicidal behavior (actual attempt, interrupted
attempt, aborted attempt, and/or preparatory acts/behavior) within the last 2 years
are exclusionary.
9. Pregnant or lactating women.
10. Abnormality in the 12-lead electrocardiogram (ECG) at screening that in the opinion
of the investigator increases the risk of participating in the study, such as a
corrected QT Fridericia (QTcF) interval >430 msec for males or >450 msec for
females.
11. A history of additional risk factors for Torsade de Pointe (eg, heart failure,
hypokalemia, family history of long QT syndrome).
12. The use of concomitant medications within 24 weeks prior to Day 1 and/or during the
study or the equivalent of 5 half-lives that prolong the QT/QTc interval, eg, Class
1 antiarrhythmics (eg, quinidine, disopyramide, procainamide) and Class 3
antiarrhythmics (eg, amiodarone, sotalol), first generation antihistamines (such as
diphenhydramine, hydroxyzine, astemizole, terfenadine, and ebastine), antipsychotics
known to prolong QT interval, and antimalarials (eg, mefloquine, quinine), tricyclic
antidepressants (eg, AMT), tetracyclic antidepressants (eg, maprotiline), cisapride.
13. The use of monoamine oxidase inhibitors within 24 weeks (or the equivalent of 5
half-lives) prior to Day 1 and/or during the study.
14. The use of opioids within 4 weeks (or the equivalent of 5 half lives) prior to Day 1
and/or during the study.
15. History of illicit drug use or confirmed drugs of abuse at screening. Positive urine
drug screen for prescribed medication is allowed at the discretion of the
investigator.
16. Patients likely to require neurotoxic chemotherapy treatment or any other treatment
during the study, which may interfere with compliance to the protocol, ability to
complete the study and study assessments except treatments authorized in inclusion
criterion #11.
17. Failure to respond to more than 2 analgesics (regardless of the route of
administration) from different drug classes (including antidepressants and
anticonvulsants) due to lack of efficacy to treat CIPN at any time in the past. The
definition of failure to respond is left to the investigator's judgement and should
be understood as exclusion of patients who are non-responding to more than 2
analgesics thought to be effective for neuropathic pain that were used at
therapeutic doses in the 6 months prior to screening visit.
18. Treatment with oral or topical AMT or nortriptyline in the past 4 weeks prior to
baseline visit.
19. Any known hypersensitivity to AMT (regardless of the route of administration) in any
salt form or to any constituent of the topical formulation.
20. Any contraindication to the use of acetaminophen/paracetamol.
21. Use of glutathione, vitamin E, or minocycline within 12 weeks of screening.
22. Any topical treatment on treated extremities for any indication, other than cosmetic
use of creams and lotions, within the previous 12 weeks prior to Baseline visit.
23. Any topical treatment for pain on extremities including use of:
1. over-the-counter capsaicin on extremities within 2 weeks of Baseline visit,
2. and/or Qutenza within 12 weeks of Baseline visit,
3. and/or nonsteroidal anti-inflammatory drugs, menthol, methyl salicylate, local
anesthetics within 1 week of screening.
24. Poor metabolizer for cytochrome P450 CYP2D6.
25. Intake in the 4 weeks preceding the screening visit of any strong inhibitor of
cytochrome P450 CYP2D6.
26. Treatment with an investigational drug in the previous 4 weeks or greater prior to
Baseline visit, according to local requirements.
27. Any condition that the investigator feels would place the patient at increased risk
if the investigational therapy is initiated, such as, but not limited to,
hyperthyroidism, convulsive disorder, advanced hepatic disease, pylorus, stenosis,
or paralytic ileus.
28. The investigator considers the patient unfit for the study as a result of the
medical interview, physical examination, or screening investigations, in particular
any status or disease making the patient unable to follow instructions.
29. The patient is unable to apply the study drug on hands or feet.
30. The patient is an employee of the investigator, study site, sponsor, or CRO with
direct involvement in the proposed study or other studies under the direction of the
investigator, study site, or sponsor, or a family member of the site employee or the
investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
South Lake Pain Institute
Address:
City:
Clermont
Zip:
34711
Country:
United States
Facility:
Name:
MGM Medical Care Research & Rehab, LLC
Address:
City:
Miami
Zip:
33173
Country:
United States
Facility:
Name:
Medsol Clinical Research Center, Inc
Address:
City:
Port Charlotte
Zip:
33952
Country:
United States
Facility:
Name:
Knight Neurology - Clinical Research
Address:
City:
Rockledge
Zip:
32955
Country:
United States
Facility:
Name:
Neuroscience Research Center, LLC.
Address:
City:
Overland Park
Zip:
66210
Country:
United States
Facility:
Name:
The Center for Cancer and Blood Disorders (CCBD)
Address:
City:
Bethesda
Zip:
20817
Country:
United States
Facility:
Name:
University of Rochester Medical Center
Address:
City:
Rochester
Zip:
14642
Country:
United States
Facility:
Name:
HD Research
Address:
City:
Bellaire
Zip:
77401
Country:
United States
Facility:
Name:
OLV Hospital Aalst: gastro-enterologie
Address:
City:
Aalst
Zip:
9300
Country:
Belgium
Facility:
Name:
Universitair Ziekenhuis Antwerpen
Address:
City:
Edegem
Zip:
2650
Country:
Belgium
Facility:
Name:
Universitair Ziekenhuis Gent (UZ Gent)
Address:
City:
Gent
Zip:
9000
Country:
Belgium
Facility:
Name:
UZ Leuven / Campus Pellenberg / Pain Center
Address:
City:
Pellenberg
Zip:
3212
Country:
Belgium
Facility:
Name:
CHU UCL Namur - site Godinne
Address:
City:
Yvoir
Zip:
5530
Country:
Belgium
Facility:
Name:
Clinitrial s.r.o.
Address:
City:
Prague
Zip:
10000
Country:
Czechia
Facility:
Name:
Praglandia s.r.o.
Address:
City:
Prague
Zip:
15000
Country:
Czechia
Facility:
Name:
Nemocnice Teplice
Address:
City:
Teplice
Zip:
41529
Country:
Czechia
Facility:
Name:
Centre Hospitalier de la Côte Basque
Address:
City:
Bayonne
Zip:
64100
Country:
France
Facility:
Name:
Institute Bergonie
Address:
City:
Bordeaux
Zip:
33076
Country:
France
Facility:
Name:
CHU de Montpellier, Hôpital Saint Eloi
Address:
City:
Montpellier
Zip:
34295
Country:
France
Facility:
Name:
Groupe Hospitalier Paris Saint Joseph
Address:
City:
Paris
Zip:
75014
Country:
France
Facility:
Name:
CHU POITIERS, Hépato-Gastro Entérologie
Address:
City:
Poitiers
Zip:
86021
Country:
France
Facility:
Name:
GODINOT Institute
Address:
City:
Reims
Zip:
51100
Country:
France
Facility:
Name:
Strasbourg Oncologie Liberale
Address:
City:
Strasbourg
Zip:
67000
Country:
France
Facility:
Name:
Hôpital Foch
Address:
City:
Suresnes
Zip:
92150
Country:
France
Facility:
Name:
Gemelli Molise S.p.a.
Address:
City:
Campobasso
Zip:
86100
Country:
Italy
Facility:
Name:
Istituto Scientifico Romagnolo per lo Studio e La cura dei Tumori Srl (IRST)
Address:
City:
Meldola
Zip:
47014
Country:
Italy
Facility:
Name:
Fondazione IRCCS Ca' Granda Ospedale -. Maggiore Policlinico
Address:
City:
Milan
Zip:
20122
Country:
Italy
Facility:
Name:
ASST Monza - Ospedale S. Gerardo di Monza
Address:
City:
Monza
Zip:
20900
Country:
Italy
Facility:
Name:
Fondazione IRCCS Policlinico San Matteo - Universita degli Studi di Pavia
Address:
City:
Pavia
Zip:
27100
Country:
Italy
Facility:
Name:
Azienda Ospedaliera San Camillo-Forlanini
Address:
City:
Roma
Zip:
00152
Country:
Italy
Facility:
Name:
Przychodnia Lekarska "Komed" Roman Karaszewski Oddzial Chemioterapii Jednego Dnia
Address:
City:
Konin
Zip:
62500
Country:
Poland
Facility:
Name:
Niepubliczny Zaklad Opieki Zdrowotnej Poradnia Leczenia Bolu Przewleklego
Address:
City:
Tychy
Zip:
43100
Country:
Poland
Facility:
Name:
ClinHouse sp z o.o. - ClinHouse Centrum Medyczne
Address:
City:
Zabrze
Zip:
41807
Country:
Poland
Facility:
Name:
Instytut "Centrum Zdrowia Matki Polki" Klinika Onkologii
Address:
City:
Łódź
Zip:
93338
Country:
Poland
Facility:
Name:
Hospital de la Santa Creu I de Sant Pau
Address:
City:
Barcelona
Zip:
08041
Country:
Spain
Facility:
Name:
Hospital Universitari de Bellvitge
Address:
City:
Barcelona
Zip:
08907
Country:
Spain
Facility:
Name:
Hospital Universitario Reina Sofia
Address:
City:
Córdoba
Zip:
14004
Country:
Spain
Facility:
Name:
Complejo Hospitalarion de Jaen
Address:
City:
Jaén
Zip:
23007
Country:
Spain
Facility:
Name:
Hospital General Universitario Gregorio Maranon
Address:
City:
Madrid
Zip:
28007
Country:
Spain
Facility:
Name:
Hospital Ruber Internacional
Address:
City:
Madrid
Zip:
28034
Country:
Spain
Facility:
Name:
Madrid Sanchinarro Hospital
Address:
City:
Madrid
Zip:
28050
Country:
Spain
Facility:
Name:
Hospital Universitari Sant Joan de Reus
Address:
City:
Reus
Zip:
43204
Country:
Spain
Facility:
Name:
Unidad de Investigacion Clinica FINCIVO
Address:
City:
Valencia
Zip:
46009
Country:
Spain
Start date:
February 28, 2023
Completion date:
September 2024
Lead sponsor:
Agency:
AlgoTherapeutix
Agency class:
Industry
Source:
AlgoTherapeutix
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05593614
