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

Study Overview
=================
Brief Summary
-----------------
Escalating single-dose design study to determine the safety, tolerability, and analgesic activity of KLS-2031

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.

Official Title
-----------------
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

Conditions
-----------------
Lumbosacral Radiculopathy

Intervention / Treatment
-----------------
* Drug: KLS-2031
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: To be eligible for the study, subjects must meet all of the following criteria at the screening visit: 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. The subject may be male or female but must be between the ages of 18 and 75 years, inclusive. The subject must have a body mass index of ≤35 kg/m2. The subject must have a diagnosis of pain due to LSR The duration of pain since onset is ≥6 months. Exclusion Criteria: The subject has: 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). 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). 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. 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. 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. 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).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>KLS-2031 low dose(1x10^11 VG/DRG) or Placebo | Drug: KLS-2031<br>* KLS-2031 administered by transforaminal epidural injection<br>Other: Placebo<br>* Saline solution administered by transforaminal epidural injection<br>|
| Experimental: Cohort 2<br>KLS-2031 medium dose(1x10^12 VG/DRG) or Placebo | Drug: KLS-2031<br>* KLS-2031 administered by transforaminal epidural injection<br>Other: Placebo<br>* Saline solution administered by transforaminal epidural injection<br>|
| Experimental: Cohort 3<br>KLS-2031 high dose(1x10^13 VG/DRG) or Placebo | Drug: KLS-2031<br>* KLS-2031 administered by transforaminal epidural injection<br>Other: Placebo<br>* Saline solution administered by transforaminal epidural injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lumbosacral Radiculopathy, LSR