First-In-Human Study of AK1320 Encapsulated Microspheres (AK1320 MS)

Study Overview
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Brief Summary
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The safety and efficacy of AK1320 MS will be evaluated in patients with degenerative spondylolisthesis and concomitant symptomatic spinal stenosis who are undergoing decompression and single level instrumented posterolateral lumber autograft fusion surgery.

Detailed Description
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This will be a first in human Phase I, ascending dose, multi-center, randomized patient study evaluating the efficacy, safety, PK of AK1320 MS. The study will enroll up to 4 dose escalating cohorts with each cohort having 2 treatment groups, the AK1320 MS group (n=7) and the Control group (n=3).

Official Title
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First-In-Human Study of AK1320 Encapsulated Microspheres (AK1320 MS) In Subjects With Degenerative Spondylolisthesis and Concomitant Symptomatic Spinal Stenosis Who Are Undergoing Decompression And Single Level Instrumented Posterolateral Lumbar Autograft Fusion Surgery

Conditions
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Degenerative Spondylolisthesis, Spinal Stenosis

Intervention / Treatment
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* Drug: AK1320 MS
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Involved level L1 to S1 Use of local autologous bone only. Degenerative spondylolisthesis up to Meyerding's Classification Grade 1 or 2. Moderate or higher disability as assessed by Oswestry Disability Index. Neurogenic claudication and/or radiculopathy with or without back pain. Male or female over 22 years of age and less than 81 years of age. Exclusion Criteria: Prior lumbar decompression or spine fusion attempt (any level). Undergoing concurrent interbody fusion. Requires spinal fusion at more than one lumbar level. Degenerative scoliosis. BMI > 40. Radiographically confirmed significant spinal instability. Active or recent (within the past two (2) years) worker's compensation litigation.

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK1320 MS<br>AK1320 MS + Local Autologous Bone + Posterior Fixation | Drug: AK1320 MS<br>* AK1320 MS + Local Autologous Bone + Posterior Fixation. Ascending Dose.<br>|
| Other: Control<br>Local Autologous Bone + Posterior Fixation | Other: Control<br>* Local Autologous Bone + Posterior Fixation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events |  | 24 months | 
| Summary of Neurological Status | Neurological status will be determined preoperatively and postoperatively using a comprehensive neurological status scale. Neurological status is based on four types of measurements: lower extremity motor, dermatomal sensation, reflexes and straight leg raise. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful Fusion | Fusion will be evaluated through CT scans. Successful fusion will be defined as complete bridging bone between the index level transverse processes with a lack of lucency or lucent lines through the fusion mass. | 24 months | 
| Oswestry Low Back Pain Disability Questionnaire (ODI) |  | 24 months | 
| 36-Item Short Form Survey (SF-36v2®) |  | 24 months | 
| AK1320 plasma concentrations |  | Pre-op(day 0), Post-op (day 0, day1), 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks and 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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degenerative spondylolisthesis, spinal stenosis, posterolateral lumber fusion surgery, autograft