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: Active, not recruiting
• Conditions: Lumbosacral Radiculopathy
• Intervention / Treatment: Drug: KLS-2031; Other: Placebo

Detailed Description

This is a first-in-human, multi-center, 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 Lumbosacral Radiculopathy.

• 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

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

To be eligible for the study, subjects must meet all of the following criteria at the screening visit:

1. The subject must be willing to provide 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 be obtained before any screening activities are conducted.
2. The subject may be male or female but must be between the ages of 18 and 75 years, inclusive.
3. The subject must have a body mass index of ≤35 kg/m2.
4. The subject must have a diagnosis of pain due to LSR
5. The duration of pain since onset is ≥6 months.

Exclusion Criteria:

1. The subject has:

   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, human immunodeficiency virus [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 is 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 prevent 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 should be discussed with the medical monitor.

2. Has lumbar stenosis with pain present solely upon walking. Presence of lumbar narrowing on MRI is acceptable if the pain is not solely present upon walking.
3. In the investigator's opinion, the subject is unable to reliably delineate or assess his/her own pain by anatomical location/distribution (eg, the subject cannot reliably tell the difference between his/her back pain and lower limb pain and cannot rate the intensity of each separately).

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; KLS-2031 low dose(1x10^11 VG/DRG) or Placebo	Drug: KLS-2031; KLS-2031 administered by transforaminal epidural injection; Other: Placebo; Saline solution administered by transforaminal epidural injection
Experimental: Cohort 2; KLS-2031 medium dose(1x10^12 VG/DRG) or Placebo	Drug: KLS-2031; KLS-2031 administered by transforaminal epidural injection; Other: Placebo; Saline solution administered by transforaminal epidural injection
Experimental: Cohort 3; KLS-2031 high dose(1x10^13 VG/DRG) or Placebo	Drug: KLS-2031; KLS-2031 administered by transforaminal epidural injection; Other: Placebo; Saline solution administered by transforaminal epidural injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with treatment-related adverse event	Week 1, Week 2, Week 4, Week 12, Week 26, Week 52

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with treatment-related adverse event	Week 78, Week 104
Number of subjects with treatment-related adverse event by transforaminal epidural injection as measured by the occurrence of injection site reactions	Week 1, Week 2, Week 4, Week 12, Week 26, Week 52, Week 78, Week 104
Change from baseline in weekly mean of the average daily pain score	Week 1, Week 2, Week 4, Week 12, Week 26, Week 52, Week 104
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
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 103
Number and percentage of subjects who are much improved or very much improved from baseline	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
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, Week 78, Week 104
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
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

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2020
• Primary Completion (Anticipated): October 30, 2022
• Study Completion (Anticipated): October 30, 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): October 6, 2022
• Last Update Submitted That Met QC Criteria: October 5, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Lumbosacral Radiculopathy; LSR
• 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