Single Ascending Doses Study of KLS-2031 in Subjects With Neuropathic Pain From Lumbosacral Radiculopathy

A Phase 1/2a, First-in-Human, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Therapeutic Activity of Single Ascending Doses of KLS-2031 Administered by Transforaminal Epidural Injection in Patients With Neuropathic Pain From Lumbosacral Radiculopathy

Escalating single-dose design study to determine the safety, tolerability, and analgesic activity of KLS-2031

Study Overview

• Status: Completed
• Conditions: Neuropathic Pain From Lumbosacral Radiculopathy
• Intervention / Treatment: Drug: KLS-2031; Other: Placebo

Detailed Description

This is a first-in-human (FIH), multicenter, double-blind, placebo-controlled, parallel-group, escalating single-dose design study to determine the safety, tolerability, and analgesic activity of KLS-2031 administered by transforaminal epidural injection to subjects aged 18 to 75 years with neuropathic pain due to LSR.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Kolon Investigative Site : CenExel JBR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

To participate in the study, subjects must have met the following criteria at Visit 1 (Screening,

Day -56 to Day -15):

1. The subject signed a written informed consent for study participation including the 1-year double-blind treatment period and 1-year, open-label, long-term extension period.

   Informed consent must have been obtained before any screening activities are conducted.

2. The subject, male or female, must have been between the ages of 18 and 75 years, inclusive.
3. The subject must have had a body mass index of ≤35 kg/m².

4. The subject must have had a diagnosis of pain due to LSR, with all of the following characteristics:

   1. The subject perceived pain in 1 or both lower limbs at areas that are consistent with the area innervated by the lumbar 4 or 5 or sacral 1 (L4, L5, S1) nerve roots, with or without other sensory symptoms in the affected areas (typically, the pain may have been perceived in the buttock, thigh, calf, leg, foot, or toes). If both limbs were affected, pain had to be asymmetrical (ie, pain worse in 1 limb).
   2. Pain in the leg radiated to below the knee.
   3. Pain in the leg was worse during rest and/or at night and not solely present upon walking.
   4. The history of the pain suggested that the cause of the LSR was due to the injury of the lumbosacral nerve root(s) by degenerative disease of the vertebrae in the lumbosacral spine or associated soft tissues (including the intervertebral discs).
   5. The duration of the pain since onset was ≥6 months.
   6. Based on clinical history, the intensity of the neuropathic (leg) pain had been stable during the 4-week period before screening (the pain may have fluctuated and may have been worse at night or at rest but was present on most days of the week).
5. Pain in the leg (worse affected leg) was worse than pain in the back.

Exclusion Criteria:Subjects were excluded from the study if 1 or more of the following criteria were applicable:

1. The subject had:

   1. Neuropathic pain due to causes other than that specified in the inclusion criteria (eg, postherpetic neuralgia; painful diabetic neuropathy; mononeuritis multiplex; central poststroke pain; spinal abscess, infection, hematoma, spondylolisthesis with displacement, or malignancy; phantom limb pain; peripheral neuropathy due to alcoholism, malignancy, HIV, syphilis; drug abuse; vitamin B12 deficiency; hypothyroidism; liver disease; toxic exposure).
   2. Radicular pain at more than 1 spinal level, unstable spine, spondylolisthesis (>Grade 1), spondylolysis, caudal equina syndrome, arachnoiditis, progressive neurological deficit, moderate to severe central spinal canal stenosis (congenital or acquired) from other origins, vertebral compression fracture(s).
   3. Pain that was associated with a substantial somatic pain component in lower limbs or other parts of the body apart from the back (eg, non-neuropathic/musculoskeletal pain) or more than 1 cause or potential cause for pain symptoms in low limbs.
   4. Any painful concurrent rheumatic disease such as, but not limited to, fibromyalgia, rheumatoid arthritis, or osteoarthritis that in the investigator's opinion would have prevented the subject from reliably delineating or assessing his/her pain due to LSR. Note: Any question regarding the acceptability of the etiology of the neuropathic pain was to be discussed with the medical monitor.
2. Had lumbar stenosis with pain present solely upon walking. Presence of lumbar narrowing on MRI was acceptable if the pain was not solely present upon walking.
3. In the investigator's opinion, the subject was unable to reliably delineate or assess his/her own pain by anatomical location/distribution (eg, the subject could not reliably tell the difference between his/her back pain and lower limb pain and could not rate the intensity of each separately).
4. The subject had pain in the lower limbs solely upon walking and not at rest.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Dose 1 (low dose: 1×1011 VG/500 μL solution) or Placebo	Drug: KLS-2031; KLS-2031 administered by transforaminal epidural injection; Other: Placebo; Normal Saline (0.9%) administered by transforaminal epidural injection
Experimental: Cohort 2; Dose 2 (medium dose: 1×1012 VG/500 μL solution) or Placebo	Drug: KLS-2031; KLS-2031 administered by transforaminal epidural injection; Other: Placebo; Normal Saline (0.9%) administered by transforaminal epidural injection
Experimental: Cohort 3; Dose 3 (high dose: 1×1013 VG/500 μL solution) or Placebo	Drug: KLS-2031; KLS-2031 administered by transforaminal epidural injection; Other: Placebo; Normal Saline (0.9%) administered by transforaminal epidural injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The safety and tolerability of KLS-2031	Frequency and nature of AEs, laboratory test results, vital sign measurements, physical and complete neurological examinations, and 12-lead electrocardiograms (ECGs)	Week 1, Week 2, Week 4, Week 12, Week 26, Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Galer Neuropathic Pain Scale (Galer NPS)		Week 1, Week 2, Week 4, Week 12, Week 26, Week 52, Week 104
Number and percentage of subjects who have ≥30% and ≥50% reduction from baseline in the average daily pain score (PI-NRS)		Week 1, Week 2, Week 4, Week 12, Week 26, Week 52, Week 104
Change from baseline in the modified Modified Roland-Morris Disability Questionnaire (RMDQ) scores (back pain and leg pain)		Week 1, Week 2, Week 4, Week 12, Week 26, Week 52, Week 104
Amount of rescue medication used (in terms of dosage/day)		Week 1, Week 2, Week 4, Week 12, Week 26, Week 52
Change from baseline in the Simple Profile of Moods States (POMS) - 2 Short Form total score and domain scores		Week 1, Week 2, Week 4, Week 12, Week 26, Week 52, Week 104
Change from baseline in Daily Sleep Interference Scale (DSIS) score		Week 1, Week 2, Week 4, Week 12, Week 26, Week 52, Week 104
Change from baseline in the Short Form-36 v2 (SF-36v2) score		Week 12, Week 26, Week 52, Week 104
Long-term safety and tolerability of KLS-2031	Frequency and nature of AEs, laboratory test results, vital sign measurements, physical and complete neurological examinations, and 12-lead ECGs	Week 1, Week 2, Week 4, Week 12, Week 26, Week 52, Week 78, Week 104
Local safety and tolerability (including AEs, clinical laboratory parameters, and physical examination) of administration by transforaminal epidural injectionepidural injection as measured by the occurrence of injection site reactions	The occurrence of injection site reactions	Week 1, Week 2, Week 4, Week 12, Week 26, Week 52
Change from baseline in weekly mean of the average daily pain score	calculated as the average of the subject's last 4 available PI-NRS daily scores in the week before the study visit	Week 1, Week 2, Week 4, Week 12, Week 26, Week 52, Week 104
Time (number of weeks) to ≥30% and ≥ 50% reduction from baseline in the average daily pain score (PI-NRS)		Week 1, Week 2, Week 4, Week 12, Week 26, Week 52, Week 104
Number and percentage of subjects who are much improved or very much improved from baseline	based on the Patient Global Impression of Change (PGIC)	Week 12, Week 26, Week 52, Week 104
Time to treatment failure	, defined as the day and time a subject starts pain medication other than acetaminophen for the treatment of neuropathic pain	Week 1, Week 2, Week 4, Week 12, Week 26, Week 52
Assessment of suicidality	using the Columbia Suicide Severity Rating Scale (C-SSRS)	Week 1, Week 2, Week 4, Week 12, Week 26, Week 52

Collaborators and Investigators

• Sponsor: Kolon Life Science
• Investigators: Principal Investigator: Todd Bertoch, MD, JBR Clinical Research

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2020
• Primary Completion (Actual): October 18, 2023
• Study Completion (Actual): October 18, 2023

Study Registration Dates

• First Submitted: December 24, 2019
• First Submitted That Met QC Criteria: January 20, 2020
• First Posted (Actual): January 23, 2020

Study Record Updates

• Last Update Posted (Actual): July 29, 2024
• Last Update Submitted That Met QC Criteria: July 25, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: LSR; Lumbosacral radiculopathy; Neuropathic pain from lumbosacral radiculopathy
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Radiculopathy
• Other Study ID Numbers: KS-GIG-001-01

Drug and device information, study documents

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