EASE (Efficacy of ATX01 Study in Erythromelalgia)

NCT05917912 | Completed Phase 2 FDA Drug

• 3 other identifiers: ATX01-23-01-EM2022-003804-34161942
• Study Type: interventional
• Target: 14
• Locations: 2 countries
• Sites: 2

Brief Summary

The goal of this two-center, randomized, double-blinded, parallel-group, placebo-controlled clinical study is designed to compare the efficacy of twice daily applications of ATX01 versus placebo during two consecutive 3-week treatment periods. The primary objective is the comparison between Treatments (ATX01 15% vs. Placebo) of mean pain attack intensity score assessed for the final week of each treatment period using an 11-point Numerical Pain Rating Scale (NPRS). Mean pain attack intensity is defined as the sum of the pain intensity score of each pain attack during the last 7 full days (Day 14 to Day 20) of each Treatment Period divided by the total number of erythromelalgia pain attacks during that 7-day period. Participants will apply on feet and/or hands twice a day in the morning and in the evening, approximately 12 hours apart from the morning administration for 3 consecutive weeks each and record the pain intensity of each attack that occurs.

Conditions

Erythromelalgia

Outcome Measures

Primary Outcomes (1)

• Comparison between Treatments (ATX01 15% vs. Placebo) of mean pain attack intensity score

  Comparison between Treatments (ATX01 15% vs. Placebo) of mean pain attack intensity score assessed for the final week of each treatment period using an 11-point Numerical Pain Rating Scale (NPRS). Mean pain attack intensity is defined as the sum of the pain intensity score of each pain attack during the last 7 full days (Day 14 to Day 20) of each Treatment Period divided by the total number of erythromelalgia pain attacks during that 7-day period

  during the last 7 full days (Day 14 to Day 20) of each Treatment Period

Secondary Outcomes (11)

• Mean pain attack intensity score for complete treatment period

  through study completion, an average of 15 weeks

• Patient Global Impression of Change (PGI-C) score

  through study completion, an average of 15 weeks

• Change in pain interference with daily life using the Brief Pain Inventory - Short Form questionnaire (BPI-SF)

  through study completion, an average of 15 weeks

• Change in quality of life, measured using the EuroQol-5-Dimension (EQ-5D) instrument

  through study completion, an average of 15 weeks

• Change in Beck Depression Inventory (BDI) score.

  through study completion, an average of 15 weeks

Study Arms (2)

Sequence A

ACTIVE COMPARATOR

i)screening and randomization; ii) baseline period (3 weeks); iii) treatment period 1 with placebo(3 weeks); iv) wash-out period (3 weeks); v), treatment period 2 with ATX-01(3 weeks); vi) follow-up visit

Drug: Amitriptyline Hydrochloride; Drug: Placebo

Sequence B

ACTIVE COMPARATOR

i)screening and randomization; ii) baseline period (3 weeks); iii) treatment period 1 with ATX-01(3 weeks); iv) wash-out period (3 weeks); v), treatment period 2 with placebo (3 weeks); vi) follow-up visit

Drug: Amitriptyline Hydrochloride; Drug: Placebo

Interventions

Amitriptyline Hydrochloride DRUG

hydrogel bottle of ATX01 15% , 0,5ml (1pump) per hand, 1ml (2 pumps) per feet during 3 weeks

Sequence A; Sequence B

Placebo DRUG

hydrogel bottle of placebo , 0,5ml (1pump) per hand, 1ml (2 pumps) per feet during 3 weeks

Sequence A; Sequence B

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 18 years of age and older.
• Documented diagnosis of erythromelalgia, as characterized by redness, warmth, and burning pain of the extremities (most commonly feet), typically precipitated by heat or exercise and relieved by cooling.
• Mean pain attack intensity, measured on the 11-point NPRS, of ≥4 and ≤9 at baseline and ≥4 pain attacks per week as documented through eDiary use during the 3 weeks prior to randomization (Day -21 to Day -1).
• Use of concomitant medications, with the exception of topical agents applied to the hands or feet, are permitted if the dose has been stable for at least 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).
• Patients having signed a written informed consent prior to any study related procedure.
• 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 visit. Male patients should agree not to donate sperm until 90 calendar days after the last dose of study drug.
• Females must comply with the following in order to be enrolled:
• WOCBP with negative pregnancy test results can be enrolled only if willing to use an acceptable contraceptive method, i.e. 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.
• Or menopausal, for at least 1 year.

You may not qualify if:

• Clinical evidence of a pre-existing pain disorder in the extremities resulting from another cause than erythromelalgia, e.g. complex regional pain syndrome (CRPS), diabetic neuropathy, chemotherapy-induced peripheral neuropathy (CIPN).
• Evidence of skin breakdown, ulcers, papules and \> +2 pitting edema of the affected limbs.
• Presence of glaucoma.
• Presence of urinary retention (or significant prostatic hypertrophy at risk of urinary retention).
• History of coronary artery disease.
• History and /or presence of major depressive episode.
• The patient has suicidal risk in the opinion of the investigator based upon clinical interview and the Columbia Suicide-Severity Rating Scale.
• 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 ms for males or \>450 ms for females.
• A history of additional risk factors for Torsade de Pointe (e.g. 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 (e.g. quinidine, disopyramide, procainamide) and Class 3 antiarrhythmics (e.g. amiodarone, sotalol), antihistamines, antipsychotics known to prolong QT interval, and antimalarials (e.g. mefloquine, quinine), tricyclic antidepressants (e.g. AMT), tetracyclic antidepressants (e.g. 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.
• Use of more than 2 analgesics (regardless of the route of administration) from different drug classes (including antidepressants and antiepileptics) on top of study drug.

Sponsors & Collaborators

• AlgoTherapeutix: lead

Study Sites (2)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Universitätsklinikum Erlangen Hautklinik

Erlangen, Germany

Location

MeSH Terms

Conditions

Erythromelalgia

Interventions

Amitriptyline

Condition Hierarchy (Ancestors)

Peripheral Vascular Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Design

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

Study Record Dates

• First Submitted: June 5, 2023
• First Posted: June 26, 2023
• Study Start: June 14, 2023
• Primary Completion: February 29, 2024
• Study Completion: February 29, 2024
• Last Updated: April 18, 2024

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); US (1)