Titration Study of ABX-1431

A Randomized, Placebo-Controlled, Optimized Titration Study of ABX-1431 in Adult Patients With Peripheral Neuropathic Pain

This study is designed to identify a titration regimen of ABX-1431 in adults with neuropathic pain with satisfactory tolerability to central nervous system (CNS) adverse events (AEs). During the course of this study, each participant will take a daily dose of ABX-1431 or a matching placebo for 28 days.

Study Overview

• Status: Completed
• Conditions: Diabetic Peripheral Neuropathy; Small Fiber Neuropathy; Post Herpetic Neuralgia; Post-Traumatic Neuralgia
• Intervention / Treatment: Drug: ABX-1431; Drug: Placebo oral capsule

Detailed Description

This is a double-blind, placebo-controlled, optimized titration study of ABX-1431 HCl. The study will explore whether patients experiencing ABX-1431-related CNS AE accommodate or become tolerant to them with continued dosing. The efficacy of ABX-1431 in treating neuropathic pain will be assessed by the change from baseline in pain intensity scores using numerical rating scale (NRS-11).

All patients will undergo a screening visit for enrollment criteria. Eligible patients will be treated with daily medication for 28 days which will include some treatment with placebo and some treatment with ABX-1431 HCl. Patients will record their daily average pain using a paper numerical rating scale (NRS-11).

This study will enroll up to 32 patients with peripheral neuropathic pain due to one of the four following diagnostic groups: post-herpetic neuralgia, diabetic peripheral neuropathy, small fiber neuropathy or post-traumatic neuropathic pain.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• Moldova, Republic of
  • Chisinau, Moldova, Republic of, MD-2025
    • Republican Clinical Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Patient is a male or female over the age of 18 years of age at the Screening Visit.

• Patient has a peripheral neuropathic pain in one of the following diagnostic groups that is persistent for > 3 months

  • Post-herpetic neuralgia
  • Diabetic peripheral neuropathy
  • Small fiber neuropathy
  • Post-traumatic neuropathic pain
• Patient's median NRS-11 pain intensity score must be ≥ 4 during the baseline period
• If a patient enters the trial on daily background neuropathic pain medications, then the patient must be on stable dose of medications for at least 30 days before enrollment and throughout the study.
• Patient is able to understand and comply with the protocol procedures for the entire trial and must give written informed consent.
• Men and Women must agree to a medically approved contraceptive regimen.

Key Exclusion Criteria:

• Patient is taking potent cytochrome P450 3A4/5 inducers or inhibitors
• Patient has received injection therapies (e.g., botulinum toxin, anesthetic or nerve block) or transcutaneous electrical stimulation to control pain in the past 60 days
• Patient has evidence of alcohol, drug or chemical abuse in the year before the Screening Visit.
• Patient is a lactating or pregnant female or a female who intends to become pregnant within 90 days following the last dose of investigational product.
• Patient has specific laboratory abnormalities

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ABX-1431; One or more oral capsules containing 2 mg or 10 mg or 50 mg of ABX-1431 HCl or matching placebo are administered daily to enrolled patients. Patients will undergo a blinded dose escalation. All patients will receive placebo on some days to assess safety and neuropathic pain. Patients will undergo an optimized titration of ABX-1431 HCl with the daily dose between 8 mg and 24 mg of ABX-1431. Each patients dose will be determined by the Investigator based on assessment of adverse events.	Drug: ABX-1431; Capsules of either 2mg, 10mg, or 50mg
Placebo Comparator: Placebo oral capsule; One or more oral capsules containing placebo are administered daily to enrolled patients. Patients will undergo a blinded dose escalation. All patients will receive placebo on some days to assess safety and neuropathic pain. Patients will undergo an optimized titration of placebo. Each patients dose will be determined by the Investigator based on assessment of adverse events.	Drug: Placebo oral capsule; placebo to match

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify a titration regimen of ABX-1431	The number of patients unable to continue due to central nervous system (CNS) adverse events (AEs) while exceeding mean plasma ABX-1431 AUC_0-24 of 190 ng*hr/ml or inhibiting 2-arachidonoylglycerol (2-AG) hydrolysis in peripheral blood mononuclear cells (PBMC) by more than 62% time-weighted inhibition over 24-hours.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerance to ABX-1431 related CNS AEs determined by whether or not AEs resolve with continued dosing		28 days
Numerical Rating Scale (NRS-11)	Change from Baseline in Pain Scores on the Numerical Rating Scale-11 (NRS-11) at 20 days.	20 days

Collaborators and Investigators

• Sponsor: Abide Therapeutics
• Investigators: Principal Investigator: Vitale Lisnic, PhD, Arensia Exploratory Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2017
• Primary Completion (Actual): May 7, 2019
• Study Completion (Actual): May 7, 2019

Study Registration Dates

• First Submitted: February 9, 2018
• First Submitted That Met QC Criteria: February 26, 2018
• First Posted (Actual): February 27, 2018

Study Record Updates

• Last Update Posted (Actual): July 12, 2019
• Last Update Submitted That Met QC Criteria: July 10, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Neuralgia; Peripheral Nervous System Diseases; Neuralgia, Postherpetic; Small Fiber Neuropathy
• Other Study ID Numbers: ABX-1431_PN014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No