Novel Soluble Epoxide Hydrolase Inhibitor for Neuropathic Pain in Patients With Spinal Cord Injury

Spinal Cord Injuries Clinical Trial

Official title:

Development of a Novel Soluble Epoxide Hydrolase Inhibitor as a Strategy for Treating Neuropathic Pain in Patients With SCI

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06438471
• Other study ID #: EC5026-1-04
• Status: Recruiting
• Phase: Phase 1
• Start date: July 2024
• Est. completion date: July 2025

Study information

• Verified date: May 2024
• Source: EicOsis Human Health Inc.
• Contact: Laura Carbone, MD, MS, FACP
• Phone: 706-721-6909
• Email: LCARBONE[@]augusta.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to evaluate safety and tolerability of multiple oral doses of EC5026 in male and female patients with neuropathic pain due to spinal cord injury. The main question it aims to answer is whether EC5026 is safe and well tolerated in SCI patients with neuropathic pain. In addition, this trial will also study the effects of EC5026 on pain.

Researchers will compare EC5026 to placebo.

Participants will be asked to:

• Take EC5026 or placebo in a masked fashion, once daily, for 14 consecutive days.

• Undergo physical exams, vital signs assessments, ECGs, and blood draws

• Complete assessments of pain, sleep, functional status, and perception of change

Description:

EC5026 has been shown to be effective in preclinical pain models of pain, including inflammatory and neuropathic pain subtypes. Three Phase 1 studies of EC5026 have been conducted in healthy volunteers; a Phase 1a Single Ascending Dose (SAD) study, a Phase 1a Fed-Fasted study, and a Phase 1b Multiple Ascending Dose (MAD) study. The Phase 1b MAD study evaluated the safety, tolerability, and PK of 2 sequential ascending dose regimens of oral EC5026, administered once daily for 7 consecutive days, in healthy volunteers. The present study will evaluate the safety and tolerability, as well as target engagement and pharmacodynamics, of EC5026 administered as multiple doses in subjects with neuropathic pain due to spinal cord injury.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: July 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Each subject must meet all of the following criteria to be enrolled in this study:

1. Male and female United States Veterans 18 and older.

2. Subjects must be willing to provide written informed consent to participate in the study.

3. Subjects must be able to provide own transportation to study site every day for the duration of the study.

4. Subjects must have a complete or incomplete C2-T12 SCI of at least 12 months duration, with below-level neuropathic pain identified by the International Spinal Cord Injury Pain (ISCIP) classification criteria.

5. Subjects must have completed a minimum of 6 of the 7 daily assessments for average and worst daily pain prior to final screening, using an 11-point numerical rating scale (NRS) for average daily pain intensity, and the arithmetic average daily SCI neuropathic pain score must be =4 and =9, with a standard deviation less than or equal to 1.2.

Daily pain assessment screenings will be done over the phone with the study coordinator after informed consent is obtained.

6. Subjects must be in overall stable condition, as determined by pre-study medical history, physical examination, clinical laboratory tests, and 12-lead ECG measurements.

7. Subjects must have normal or not clinically significant clinical laboratory test results, as determined by the study investigator, including coagulation panel, blood cell counts, comprehensive metabolic panel analytes, and creatinine clearance (60 cm3/min or greater). Clinical laboratory tests results that are consistent with known, stable comorbidities will be allowed as long as the comorbidities do not represent an exclusion criteria per se.

8. Subjects must have a negative screening for HIV, Hepatitis C, and Hepatitis B within 30 days of randomization.

9. Subjects must have a negative urinary drug screen (UDS) for illicit drugs (marihuana/THC are allowed) and serum ethanol level <80 mg/dL.

10. Male subjects who are not surgically sterile (vasectomized) and their female sexual partners must agree to use contraception during the study period and for 2 months afterward.

11. Male subjects must not donate sperm during the study and for 12 months after receiving the last dose of study drug.

12. Female subjects must be non-pregnant, non-lactating, and either postmenopausal for at least 1 year, or surgically sterile (bilateral tubal ligation ('clipping or tying tubes' or hysterectomy) for at least 3 months, or they must agree to use a highly effective contraception method (less than 1 pregnancy per 100 people using the method for one year), from 28 days and/or their last confirmed menstrual period prior to study enrollment (whichever is longer) until 2 months after clinic discharge.

Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded from the study:

1. Ventilator-dependent subjects, with the exception of nocturnal use of CPAP or BiPAP.

2. Subjects with pain that is not present every day (chronic) or where the pain description does not have a classic neuropathic phenotype.

3. Subjects with other chronic neuropathic pain conditions, including painful diabetic neuropathy, HIV-associated neuropathic pain, chemotherapy or ethanol-associated neuropathy.

4. Subjects with other pain syndromes that may confound assessment or self-evaluation of the SCI neuropathic pain.

5. Subjects with only negative symptoms, defined as numbness without clear evidence of spontaneous pain, either constant or episodic.

6. Subjects using opioid medications on a regular basis or pro re nata (PRN). Non-opioid pain medications will be allowed if at a fixed stable dose for more than 1 month prior to Screening with no anticipation of the dose changing during the study, and if they do not interfere with the subject's ability to rate pain as per Investigator's discretion. Allowed non-opioid medications include gabapentin, pregabalin, duloxetine, acetaminophen, ibuprofen, celecoxib, meloxicam, other antidepressants including amitriptyline and other antiepileptics, as well as topical capsaicin and topical lidocaine.

7. Subjects with active Hepatitis A, Hepatitis B and/or Hepatitis C.

8. Subjects with any clinically unstable or significant cardiovascular (including acute coronary syndrome within the prior year to Screening), renal, hepatic, respiratory, gastrointestinal, hematological, endocrine, or infectious disease (including HIV infection).

9. Subjects with clinically significant abnormalities on screening vital signs, laboratory tests, and/or ECG. Subjects with poor venous access will also be excluded.

10. Subjects with a history of disorders of the hypothalamic-pituitary-adrenal axis, including adrenal insufficiency and Cushing's.

11. Subjects who have used chemotherapy agents, or who have a personal history of cancer or cancer in first degree relatives suggestive of elevated cancer risk, other than nonmetastatic skin cancer that has been completely excised, within 5 years prior to Screening.

12. Subjects with a history of bacterial, fungal, or viral infection requiring treatment with antibiotics, antifungal agents, or antivirals within 1 month prior to randomization.

13. Subjects who have used (within 14 days of randomization) or plan on using during the duration of the study any prescription or over-the-counter drugs that are moderate-strong CYP3A4 inducers or inhibitors.

14. Subjects who have used (within 14 days of randomization) or plan on using during the duration of the study any dietary aids, supplements, or foods that are moderate-strong CYP3A4 inhibitors (e.g., grapefruit juice).

15. Subjects with difficulty in swallowing oral medications.

16. Subjects with serious psychosocial comorbidities as determined by the Investigator.

17. Subjects with current cognitive or major psychiatric disorders, or any other condition that could interfere with compliance with study procedures.

18. Subjects with a positive drug or alcohol test (>80 mg/dL) during Screening and/or admission (a positive THC test will be allowed as long as it consists of minimal social use, per discretion of Investigator), or with a recent history of binge drinking within 1 week of randomization.

19. Subjects who have used any other investigational drug within 1 month prior to enrollment. If the investigational drug is known to have a long half life, a longer washout period will be done.

20. Subjects with a presence or history of active gastrointestinal disorder, including esophageal or gastroduodenal ulceration, or renal, hepatic, or coagulant disorder within 1 month prior to enrollment.

21. Subjects with a family history of significant cardiac disease (i.e., sudden death in first degree relative; myocardial infarction before the age of 50).

22. Subjects with confirmed COVID-19, or suspected COVID-19 (e.g., developed symptoms of a respiratory infection such as cough, sore throat, shortness of breath, or fever, but did not get tested for COVID-19) within 30 days of randomization.

23. Subjects who have received a COVID-19 vaccine within 30 days of randomization or are planning on receiving it during the study duration.

24. Subjects who are not Veterans

Related Conditions & MeSH terms

• Neuralgia
• Neuropathic Pain
• Spinal Cord Injuries

Intervention

Drug:
• EC5026 oral tablet
There will be two ascending dose regimens of EC5026, which will be administered over two consecutive Treatment Periods. During each Treatment Period, EC5026 will be administered orally once daily for 7 consecutive days, with a loading dose on Day 1 and a maintenance dose on Days 2-7 of each treatment period. All study subjects will be enrolled in both Treatment Periods and will receive both dose regimens consecutively, for a total duration of 14 days. Oral doses of EC5026 tested in each Treatment Period: Treatment Period 1: 6 mg loading dose on Day 1 / 2 mg Maintenance dose on Days 2-7 Treatment Period 2: 8 mg loading dose on Day 8 / 4 mg Maintenance dose on Days 9-14
• Placebo oral tablet
Participants will be administered a matching oral placebo for 14 consecutive days.

Locations

Country	Name	City	State
United States	AU Medical Center	Augusta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
EicOsis Human Health Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Effects of 2 ascending multiple dose regimens of EC5026 versus placebo on plasma levels of EC5026	Standard validated EC5026 measurement platform will be used.	30 days
Other	Effects of 2 ascending multiple dose regimens of EC5026 versus placebo on oxylipin biomarkers.	Standard validated oxylipin measurement platform will be used.	30 days
Other	Effects of 2 ascending multiple dose regimens of EC5026 versus placebo on target engagement biomarkers.	Target engagement biomarkers will include epoxi fatty acids(EpFA):diol ratio	30 days
Other	Effects of 2 ascending multiple dose regimens of EC5026 versus placebo on inflammatory biomarkers: C-Reactive Protein		30 days
Other	Effects of 2 ascending multiple dose regimens of EC5026 versus placebo on inflammatory biomarkers: IL-6		30 days
Other	Effects of 2 ascending multiple dose regimens of EC5026 versus placebo on inflammatory biomarkers: TNF alpha		30 days
Other	Change in average daily pain from baseline to Day 4	The average daily pain will be measured as part of the Brief Pain Inventory - Short Form (BPI-SF). This scale uses a 11-point numeric rating scale (NRS) from 0 to 10 to rate pain from "no pain" (score = 0) to "pain as bad as you can imagine" (score = 10).	4 days
Other	Change in average daily pain from baseline to Day 8	The average daily pain will be measured as part of the Brief Pain Inventory - Short Form (BPI-SF). This scale uses a 11-point numeric rating scale (NRS) from 0 to 10 to rate pain from "no pain" (score = 0) to "pain as bad as you can imagine" (score = 10).	8 days
Other	Change in average daily pain from baseline to Day 11	The average daily pain will be measured as part of the Brief Pain Inventory - Short Form (BPI-SF). This scale uses a 11-point numeric rating scale (NRS) from 0 to 10 to rate pain from "no pain" (score = 0) to "pain as bad as you can imagine" (score = 10).	11 days
Other	Change in average daily pain from baseline to Day 14	The average daily pain will be measured as part of the Brief Pain Inventory - Short Form (BPI-SF). This scale uses a 11-point numeric rating scale (NRS) from 0 to 10 to rate pain from "no pain" (score = 0) to "pain as bad as you can imagine" (score = 10).	14 days
Other	Change in average daily pain from baseline to Day 21	The average daily pain will be measured as part of the Brief Pain Inventory - Short Form (BPI-SF). This scale uses a 11-point numeric rating scale (NRS) from 0 to 10 to rate pain from "no pain" (score = 0) to "pain as bad as you can imagine" (score = 10).	21 days
Other	Change in average daily pain from baseline to Day 28	The average daily pain will be measured as part of the Brief Pain Inventory - Short Form (BPI-SF). This scale uses a 11-point numeric rating scale (NRS) from 0 to 10 to rate pain from "no pain" (score = 0) to "pain as bad as you can imagine" (score = 10).	28 days
Other	Change in worst daily pain from baseline to Day 4.	The worst daily pain will be measured as part of the Brief Pain Inventory - Short Form (BPI-SF). This scale uses a 11-point numeric rating scale (NRS) from 0 to 10 to rate pain from "no pain" (score = 0) to "pain as bad as you can imagine" (score = 10).	4 days
Other	Change in worst daily pain from baseline to Day 8.	The worst daily pain will be measured as part of the Brief Pain Inventory - Short Form (BPI-SF). This scale uses a 11-point numeric rating scale (NRS) from 0 to 10 to rate pain from "no pain" (score = 0) to "pain as bad as you can imagine" (score = 10).	8 days
Other	Change in worst daily pain from baseline to Day 11.	The worst daily pain will be measured as part of the Brief Pain Inventory - Short Form (BPI-SF). This scale uses a 11-point numeric rating scale (NRS) from 0 to 10 to rate pain from "no pain" (score = 0) to "pain as bad as you can imagine" (score = 10).	11 days
Other	Change in worst daily pain from baseline to Day 14.	The worst daily pain will be measured as part of the Brief Pain Inventory - Short Form (BPI-SF). This scale uses a 11-point numeric rating scale (NRS) from 0 to 10 to rate pain from "no pain" (score = 0) to "pain as bad as you can imagine" (score = 10).	14 days
Other	Change in worst daily pain from baseline to Day 21.	The worst daily pain will be measured as part of the Brief Pain Inventory - Short Form (BPI-SF). This scale uses a 11-point numeric rating scale (NRS) from 0 to 10 to rate pain from "no pain" (score = 0) to "pain as bad as you can imagine" (score = 10).	21 days
Other	Change in worst daily pain from baseline to Day 28.	The worst daily pain will be measured as part of the Brief Pain Inventory - Short Form (BPI-SF). This scale uses a 11-point numeric rating scale (NRS) from 0 to 10 to rate pain from "no pain" (score = 0) to "pain as bad as you can imagine" (score = 10).	28 days
Other	Change in Neuropathic Pain Symptom Inventory (NPSI) total score from baseline to Day 4.	The Neuropathic Pain Symptom Inventory (NPSI) is a questionnaire that assesses neuropathic pain. The total score on the NPSI ranges from 0 to 100, with higher scores indicating more severe pain.	4 days
Other	Change in Neuropathic Pain Symptom Inventory (NPSI) total score from baseline to Day 8.	The Neuropathic Pain Symptom Inventory (NPSI) is a questionnaire that assesses neuropathic pain. The total score on the NPSI ranges from 0 to 100, with higher scores indicating more severe pain.	8 days
Other	Change in Neuropathic Pain Symptom Inventory (NPSI) total score from baseline to Day 11.	The Neuropathic Pain Symptom Inventory (NPSI) is a questionnaire that assesses neuropathic pain. The total score on the NPSI ranges from 0 to 100, with higher scores indicating more severe pain.	11 days
Other	Change in Neuropathic Pain Symptom Inventory (NPSI) total score from baseline to Day 14.	The Neuropathic Pain Symptom Inventory (NPSI) is a questionnaire that assesses neuropathic pain. The total score on the NPSI ranges from 0 to 100, with higher scores indicating more severe pain.	14 days
Other	Change in Neuropathic Pain Symptom Inventory (NPSI) total score from baseline to Day 21.	The Neuropathic Pain Symptom Inventory (NPSI) is a questionnaire that assesses neuropathic pain. The total score on the NPSI ranges from 0 to 100, with higher scores indicating more severe pain.	21 days
Other	Change in Neuropathic Pain Symptom Inventory (NPSI) total score from baseline to Day 28.	The Neuropathic Pain Symptom Inventory (NPSI) is a questionnaire that assesses neuropathic pain. The total score on the NPSI ranges from 0 to 100, with higher scores indicating more severe pain.	28 days
Primary	Incidence of Adverse Events (AEs) and Serious Adverse Events (SAE) [Safety and Tolerability]	All AEs reported or observed during the study will be recorded on the electronic case report forms (eCRF). Information to be collected includes drug treatment, type of event, time of onset, dosage, investigator-specified assessment of severity and relationship to study drug, time of resolution of the event, seriousness, any required treatment or evaluations, and outcome. Any AEs resulting from concurrent illnesses, reactions to concurrent illnesses, reactions to concurrent medications, or progression of disease states must also be reported. All AEs will be followed until they are resolved, stable, or judged by the investigator to be not clinically significant. The Medical Dictionary for Regulatory Activities will be used to code all AEs.	30 days