Efficacy and Safety of ATX01 in Adult Patients With CIPN (Chemotherapy-induced Peripheral Neuropathy)

NCT05593614 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: ATX01-22-01-CIPN2022-000435-23
• Study Type: interventional
• Target: 276
• Locations: 7 countries
• Sites: 43

Brief 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.

Conditions

Chemotherapy-induced Peripheral Neuropathy

Outcome Measures

Primary Outcomes (1)

• Change from baseline to Week 12 in the weekly mean of the daily NPRS score assessing average pain intensity in target study extremities related to CIPN in the past 24 hours.

  12 weeks

Secondary Outcomes (12)

• Percentage of patients achieving ≥30% pain reduction from baseline in the weekly mean NPRS average pain intensity related to CIPN at Week 12

  12 weeks

• Percentage of patients achieving ≥50% pain reduction from baseline in the weekly mean NPRS average pain intensity related to CIPN at Week 12.

  12 weeks

• Mean change from baseline to each visit in tingling/pins and needles intensity and numbness intensity in target study extremities as measured by the numerical rating scale (NRS) assessing each symptom

  4 weeks, 8 weeks, 12 weeks

• Proportion of patients achieving various percentages of reduction in average pain intensity in target study extremities (cumulative responder curve) throughout the study.

  4 weeks, 8 weeks, 12 weeks

• Proportion of patients achieving various percentages of reduction in worst pain intensity in target study extremities (cumulative responder curve) throughout the study.

  4 weeks, 8 weeks, 12 weeks

Study Arms (3)

ATX01 10%

EXPERIMENTAL

A bottle of hydrogel formulation containing 10% amitriptyline hydrochloride w/w for topical use on the hands and/or feet, morning and night for 3 months.

Drug: ATX01 10%

ATX01 15%

EXPERIMENTAL

A bottle of hydrogel formulation containing 15% amitriptyline hydrochloride w/w for topical use on the hands and/or feet, morning and night for 3 months.

Drug: ATX01 15%

ATX01 Placebo

PLACEBO COMPARATOR

A bottle of hydrogel formulation containing no active ingredient, for topical use on the hands and/or feet, morning and night for 3 months.

Drug: Placebo

Interventions

ATX01 10% DRUG

A 100 mL bottle of hydrogel formulation containing 10% amitriptyline hydrochloride w/w

ATX01 10%

ATX01 15% DRUG

A 100 mL bottle of hydrogel formulation containing 15% amitriptyline hydrochloride w/w

ATX01 15%

Placebo DRUG

A 100 mL bottle of hydrogel formulation containing no active substance

ATX01 Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients of 18 years and older.
• Patients having signed a written informed consent prior to any study-related procedure.
• Body mass index of 18 to 35 kg/m2 (inclusive).
• With an estimated life expectancy ≥6 months at study entry.
• 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).
• 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.
• Patients with CIPN pain for ≥24 weeks at the time of the screening visit.
• 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.
• Patients with symmetrical stocking or glove distribution pain, NPRS (≤1 point difference) in the target study extremities at screening.
• Neuropathic Pain (DN4) score ≥4 in the target study extremities (hands or feet) at the screening visit
• 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).
• 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.
• Females must comply with the following in order to be enrolled:
• 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.
• Or surgically sterilized for at least 6 months.

You may not qualify if:

• 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.
• 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.
• 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 \[only on the feet if the study drug is not applied on the hands\]).
• Presence of glaucoma.
• Presence of urinary retention (or significant prostatic hypertrophy at risk of urinary retention).
• Angina or myocardial infarction in the year preceding screening visit.
• History and/or presence of major depressive episode. Patients with a medical history of bipolar disorder, alcohol abuse, or psychotic disorder are also excluded.
• Pregnant or lactating women.
• 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.
• A history of additional risk factors for Torsade de Pointe (eg, heart failure, hypokalemia, family history of long QT syndrome).
• 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.
• 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.
• The use of opioids within 4 weeks (or the equivalent of 5 half lives) prior to Day 1 and/or during the study.
• 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.
• Treatment with oral or topical AMT or nortriptyline in the past 4 weeks prior to baseline visit.

Sponsors & Collaborators

• AlgoTherapeutix: lead

Study Sites (43)

South Lake Pain Institute

Clermont, Florida, 34711, United States

Location

MGM Medical Care Research & Rehab, LLC

Miami, Florida, 33173, United States

Location

Medsol Clinical Research Center, Inc

Port Charlotte, Florida, 33952, United States

Location

Knight Neurology - Clinical Research

Rockledge, Florida, 32955, United States

Location

Neuroscience Research Center, LLC.

Overland Park, Kansas, 66210, United States

Location

The Center for Cancer and Blood Disorders (CCBD)

Bethesda, Maryland, 20817, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

HD Research

Bellaire, Texas, 77401, United States

Location

OLV Hospital Aalst: gastro-enterologie

Aalst, 9300, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

Universitair Ziekenhuis Gent (UZ Gent)

Ghent, 9000, Belgium

Location

UZ Leuven / Campus Pellenberg / Pain Center

Pellenberg, 3212, Belgium

Location

CHU UCL Namur - site Godinne

Yvoir, 5530, Belgium

Location

Clinitrial s.r.o.

Prague, 10000, Czechia

Location

Praglandia s.r.o.

Prague, 15000, Czechia

Location

Nemocnice Teplice

Teplice, 41529, Czechia

Location

Centre Hospitalier de la Côte Basque

Bayonne, 64100, France

Location

Institute Bergonie

Bordeaux, 33076, France

Location

CHU de Montpellier, Hôpital Saint Eloi

Montpellier, 34295, France

Location

Groupe Hospitalier Paris Saint Joseph

Paris, 75014, France

Location

CHU POITIERS, Hépato-Gastro Entérologie

Poitiers, 86021, France

Location

GODINOT Institute

Reims, 51100, France

Location

Strasbourg Oncologie Liberale

Strasbourg, 67000, France

Location

Hôpital Foch

Suresnes, 92150, France

Location

Gemelli Molise S.p.a.

Campobasso, 86100, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e La cura dei Tumori Srl (IRST)

Meldola, 47014, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale -. Maggiore Policlinico

Milan, 20122, Italy

Location

ASST Monza - Ospedale S. Gerardo di Monza

Monza, 20900, Italy

Location

Fondazione IRCCS Policlinico San Matteo - Universita degli Studi di Pavia

Pavia, 27100, Italy

Location

Azienda Ospedaliera San Camillo-Forlanini

Roma, 00152, Italy

Location

Przychodnia Lekarska "Komed" Roman Karaszewski Oddzial Chemioterapii Jednego Dnia

Konin, 62500, Poland

Location

Instytut "Centrum Zdrowia Matki Polki" Klinika Onkologii

Lodz, 93338, Poland

Location

Niepubliczny Zaklad Opieki Zdrowotnej Poradnia Leczenia Bolu Przewleklego

Tychy, 43100, Poland

Location

ClinHouse sp z o.o. - ClinHouse Centrum Medyczne

Zabrze, 41807, Poland

Location

Hospital de la Santa Creu I de Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitari de Bellvitge

Barcelona, 08907, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Complejo Hospitalarion de Jaen

Jaén, 23007, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Ruber Internacional

Madrid, 28034, Spain

Location

Madrid Sanchinarro Hospital

Madrid, 28050, Spain

Location

Hospital Universitari Sant Joan de Reus

Reus, 43204, Spain

Location

Unidad de Investigacion Clinica FINCIVO

Valencia, 46009, Spain

Location

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2022
• First Posted: October 25, 2022
• Study Start: February 28, 2023
• Primary Completion: September 1, 2024
• Study Completion: September 1, 2024
• Last Updated: July 16, 2024

Record last verified: 2024-01

Locations

US (8); BE (5); FR (8); IT (6); PL (4); ES (9); CZ (3)