Ricolinostat in Patients With Painful Diabetic Peripheral Neuropathy

• ClinicalTrials.gov Identifier: NCT03176472
• Recruitment Status: Completed
• First Posted: June 5, 2017
• Results First Posted: September 21, 2023
• Last Update Posted: September 21, 2023
• Sponsor: Regenacy Pharmaceuticals LLC
• Information provided by (Responsible Party): Regenacy Pharmaceuticals LLC

Tracking Information

• First Submitted Date: May 18, 2017
• First Posted Date: June 5, 2017
• Results First Submitted Date: May 30, 2023
• Results First Posted Date: September 21, 2023
• Last Update Posted Date: September 21, 2023
• Actual Study Start Date: December 7, 2020
• Actual Primary Completion Date: October 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 10, 2023)

Change in Mean Average Pain Intensity (NRS) [ Time Frame: Baseline week [Day-7 to Day 1] compared to Final week [12 Weeks] ]

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.

Original Primary Outcome Measures (submitted: June 1, 2017)

Average Pain Intensity (NRS) [ Time Frame: Baseline week [Day-7 to Day 1] compared to Final week [Day 22 to Day 28] ]

Difference between mean average pain intensity

Current Secondary Outcome Measures (submitted: August 10, 2023)

Change in Non-pain Neuropathic Signs (UENS) [ Time Frame: Baseline week [Day-7 to Day 1] compared to Week 12 ]

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.

Original Secondary Outcome Measures (submitted: June 1, 2017)

• BPI-SF pain score [ Time Frame: Day 1 to Day 28 ]
  Change in mean BPI-SF pain intensity and interference score
• NTSS-6 [ Time Frame: Day 1 to Day 28 ]
  Change in neuropathy symptoms

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ricolinostat in Patients With Painful Diabetic Peripheral Neuropathy
• Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study of Ricolinostat in Patients With Painful Diabetic Peripheral Neuropathy
• Brief Summary: 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.

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
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

double-blind

Primary Purpose: Treatment

• Condition: Painful Diabetic Peripheral Neuropathy

Intervention

• Drug: ricolinostat
  120 mg per dose in 12 mL liquid formulation
  Other Name: ACY-1215
• Drug: Placebo
  12 mL liquid formulation placebo

Study Arms

• Experimental: ricolinostat
  Ricolinostat 120 mg, taken once daily (QD) by mouth; each dose in 12 mL liquid formulation (10 mg ricolinostat per mL)
  Intervention: Drug: ricolinostat
• Placebo Comparator: placebo
  Placebo, 12 mL of liquid formulation with no active ingredient (i.e., ricolinostat), taken once daily (QD) by mouth
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 18, 2022): 282
• Original Estimated Enrollment (submitted: June 1, 2017): 450
• Actual Study Completion Date: April 28, 2023
• Actual Primary Completion Date: October 31, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03176472
• Other Study ID Numbers: REGY-DN-201
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Regenacy Pharmaceuticals LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Regenacy Pharmaceuticals LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Regenacy Pharmaceuticals LLC
• Verification Date: September 2023