Ricolinostat in Patients With Painful Diabetic Peripheral Neuropathy

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study of Ricolinostat in Patients With Painful Diabetic Peripheral Neuropathy

This is a randomized, double-blind, 2-arm, parallel group study of up to 274 evaluable patients designed to evaluate the safety and efficacy of the histone deacetylase 6 (HDAC6) inhibitor ricolinostat for painful DPN.

Study Overview

• Status: Completed
• Conditions: Painful Diabetic Peripheral Neuropathy
• Intervention / Treatment: Drug: ricolinostat; Drug: Placebo

Detailed Description

The study includes an approximately 12 week randomized, double-blind, placebo controlled Treatment period in which patients will receive either ricolinostat or placebo, followed by an approximately 12 week open label Safety Extension period during which all patients will receive ricolinostat 120 mg daily.

Prior to randomization, patients will be enrolled in a baseline Pain Observation period from Day -14 to Day -1, during which the NRS (average and worst pain) will be recorded daily using an electronic daily diary that will be completed by patients to allow patients to familiarize themselves with the pain rating procedures, and to establish a baseline and confirm eligibility to participate. Patients will also initiate daily dosing during this time to evaluate compliance eligibility for participation. A daily diary will be used by the patient to record the pain assessments and rescue medication use. A follow-up phone contact will be conducted at Day -7 to Day -5 to review diary and dosing compliance.

Following the baseline Pain Observation period, patients who meet entry criteria will be randomized in a 1:1 ratio to receive either ricolinostat or placebo. During the 12-week double-blind, placebo-controlled Treatment period, patients will return for assessments in accordance with the schedule of assessments. At the conclusion of the approximately 12 week open label Safety Extension period, patients will enter a Follow-up safety washout and assessment period, which will incorporate 2 visits at approximately 2 and 4 weeks following the final Safety Extension visit, with assessments performed as outlined in the schedule of assessments.

• Study Type: Interventional
• Enrollment (Actual): 282
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group LLC
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Arizona Research Center
  • California
    • Huntington Beach, California, United States, 92648
      • Diabetes/Lipid Management & Research Center
    • Huntington Park, California, United States, 90255
      • National Research Institute
    • La Jolla, California, United States, 92037
      • Altman Clinical and Translational Research Institute
    • Lomita, California, United States, 90717
      • Torrance Clinical Research Institute Inc
    • North Hollywood, California, United States, 91606
      • Providence Clinical Research
    • San Francisco, California, United States, 94115
      • Center for Clinical Research INC
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research Inc
  • Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida Inc
    • Lake Mary, Florida, United States, 32746
      • DeLand Clinical Research Unit
    • Maitland, Florida, United States, 32751
      • ClinCloud LLC
    • Miami, Florida, United States, 33134
      • APF Research LLC
    • Miami, Florida, United States, 33183
      • International Research Associates LLC
    • Ocoee, Florida, United States, 34761
      • Sensible Healthcare LLC
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Tampa, Florida, United States, 33634
      • Meridien Research
    • West Palm Beach, Florida, United States, 33401
      • Metabolic Research Institute Inc
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Physicians Research Associates, LLC
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Rocky Mountain Clinical Research
  • Indiana
    • Evansville, Indiana, United States, 47714
      • MediSphere Medical Research Center, LLC
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research
  • Mississippi
    • Olive Branch, Mississippi, United States, 38654
      • Olive Branch Family Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89123
      • Advanced Biomedical Research of America
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute
  • New York
    • Brooklyn, New York, United States, 11235
      • NY Scientific
  • North Carolina
    • Greensboro, North Carolina, United States, 27410
      • Triad Clinical Trials
    • Winston-Salem, North Carolina, United States, 27103
      • The Center for Clinical Research
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center
    • Summerville, South Carolina, United States, 29485
      • Palmetto Clinical Research
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
    • Houston, Texas, United States, 77030
      • Nerve And Muscle Center Of Texas
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute
    • San Antonio, Texas, United States, 78229
      • Diabetes & Glandular Disease Clinic, P.A.
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Wasatch Clinical Research LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Type 1 or Type 2 diabetes of at least 6 months with optimized and stable glycemic control during the 3 months prior to Screening
• Painful distal symmetric sensorimotor polyneuropathy due to diabetes
• Douleur Neuropathique 4 (DN4) score of ≥4
• Satisfactory diary data during the 14-day Pain Observation period determined by an algorithm that includes diary compliance, overall level of pain and day-to-day variability in pain

Exclusion Criteria:

• Pregnant or lactating
• Body Mass Index (BMI) >40 kg/m2
• Presence of any neuropathy other than DPN and/or significant risk factors for neuropathy other than diabetes
• Other pain conditions that could confound the results of this study, or other chronic pain condition(s) that could affect compliance with pain medication restrictions or confound pain assessments
• Painful DPN patients who have undergone lower limb amputations, are non-ambulatory, or whose walking is so impaired as to require a walker or other assistance for ambulation
• Have met Diagnostic and Statistical Manual of Mental Disorders V (DSM V) criteria for opioid use disorder or alcohol use disorder
• Opioid use at a dose of ≥ 30 morphine milligram equivalents on 3 or more days a week during the month prior to Screening
• Suicidal ideation/behavior as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)
• The use of marijuana or cannabidiol (CBD) during the 30 days prior to starting study drug
• Chronic use of over-the-counter capsaicin on extremities within 3 months of Screening and/or prescription Qutenza use within 6 months of Screening
• Corrected QT interval at Screening using QTcF of ≥450 msec (male) or ≥460 msec (female)
• Hemoglobin < 11.5 g/dL (female) or < 13 g/dL (male), total white blood cell count < 2500/mm3, neutrophil count < 1250/mm3, lymphocyte count < 1000/mm3, or platelet count < 100,000/mm3
• HIV positive and/or active hepatitis virus (A, B, or C) infection
• Current or previous (≤1 month of Screening) enrollment in a clinical trial involving treatment with an investigational product
• Any known recent exposure within the 14 days prior to initial Screening to coronavirus disease 2019 (COVID-19) or symptoms of COVID-19 infection or other reason to suspect COVID-19 infection as assessed by the Investigator at the time of initial Screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ricolinostat; Ricolinostat 120 mg, taken once daily (QD) by mouth; each dose in 12 mL liquid formulation (10 mg ricolinostat per mL)	Drug: ricolinostat; 120 mg per dose in 12 mL liquid formulation; Other Names: ACY-1215
Placebo Comparator: placebo; Placebo, 12 mL of liquid formulation with no active ingredient (i.e., ricolinostat), taken once daily (QD) by mouth	Drug: Placebo; 12 mL liquid formulation placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Average Pain Intensity (NRS)	Difference between mean average pain intensity using the 11-point numerical pain rating scale (NRS) consisting of pain measurement from 0-10 with 10 being the worst pain and 0 being no pain at all.	Baseline week [Day-7 to Day 1] compared to Final week [12 Weeks]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Non-pain Neuropathic Signs (UENS)	Change in non-pain neuropathic signs utilizing the Utah Early Neuropathy Score (UENS) which is a physical examination-based scale designed to assess early sensory predominant polyneuropathy. Compared with other scales, the UENS emphasizes severity and spatial distribution of pin (sharp) sensation loss in the foot and leg and focuses less on motor weakness. The UENS utilizes a numeric scale from 0-42, with higher scores indicating greater disease severity.	Baseline week [Day-7 to Day 1] compared to Week 12

Collaborators and Investigators

• Sponsor: Regenacy Pharmaceuticals LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2020
• Primary Completion (Actual): October 31, 2022
• Study Completion (Actual): April 28, 2023

Study Registration Dates

• First Submitted: May 18, 2017
• First Submitted That Met QC Criteria: June 1, 2017
• First Posted (Actual): June 5, 2017

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 18, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Neuropathic Pain; Diabetic Neuropathic Pain; DPN; HDAC6; ricolinostat; Painful Diabetic Peripheral Neuropathy
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Peripheral Nervous System Diseases; Pain; Diabetic Neuropathies; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Ricolinostat
• Other Study ID Numbers: REGY-DN-201

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