A Study to Evaluate Safety and Exploratory Efficacy of KTP-001 in Subjects With Lumbar Disc Herniation

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and exploratory efficacy of KTP-001 in subjects with lumbar disc herniation.

Detailed Description
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This study was a first-in-human, open-label, non-controlled single ascending dose study of KTP-001 in male and female subjects between the ages of 30 and 70 years with a single herniated lumbar disc. After obtaining informed consent, subjects were evaluated during a screening period of no more than 3 weeks (21 days). This study was conducted in 10 centers in the US. Subjects that met all screening requirements and inclusion criteria and none of the exclusion criteria were enrolled into the study. Overall, 24 subjects were enrolled and treated: 6 subjects in each cohort. Cohort 1 received a 5 μg/disc dose of KTP-001 by intradiscal injection. Following administration of study drug, subjects were confined to the study center for 24 hours to collect data for safety and efficacy measures and collect blood samples for safety, PK evaluation, exploratory PD and anti-KTP-001 antibody and then returned for further assessments at various intervals from weeks 1 through to month 24. After all subjects in Cohort 1 had received study drug, safety measures were evaluated by a Data and Safety Monitoring Board (DSMB) to determine whether to escalate KTP-001 administration to the next dose level. If appropriate, Cohort 2 subjects received 15 μg/disc of KTP-001, Cohort 3 subjects received 50 μg/disc of KTP-001, and Cohort 4 subjects received 150 μg/disc of KTP-001 by intradiscal injection. All safety, PK, and exploratory efficacy assessments were performed for the subjects in the subsequent cohorts as were performed for Cohort 1.

Official Title
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Open-Label, Non-controlled, Single Ascending Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Exploratory Efficacy of KTP-001 in Subjects With Lumbar Disc Herniation

Conditions
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Lumbar Disc Herniation

Intervention / Treatment
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* Drug: KTP-001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has had a single contained or noncontained (extruded) lumbar disc herniation (L3-L4, L4-L5 or L5-S1) diagnosed by clinical symptoms and/or physical findings and confirmed by MRI. Subject has leg pain with a documented positive straight leg raise (SLR) test or femoral stretch test (FST). Subject has experiences herniated disc symptoms for at least 6 weeks prior to the study without relief with pain medications and other therapies. Subject has a BMI of 18 to 35 kg/m2 Exclusion Criteria: Subject has a sequestered lumbar disc herniation or intrathecal herniation confirmed by MRI Subject has two or more symptomatic lumbar disc herniations Previous intradiscal therapeutic intervention or has had any lumbar surgery Presence of lumbar spine disease and/or deformity other than a lumbar disc herniation Active smoker or is unable to abstain from tobacco use for 2 weeks prior to study injection Subject has a history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>one time 5 μg/disc dose of KTP-001 by intradiscal injection | Drug: KTP-001<br>* KTP-001 is one time dose intradiscally.<br>|
| Experimental: Cohort 2<br>one time 15 μg/disc dose of KTP-001 by intradiscal injection | Drug: KTP-001<br>* KTP-001 is one time dose intradiscally.<br>|
| Experimental: Cohort 3<br>one time 50 μg/disc dose of KTP-001 by intradiscal injection | Drug: KTP-001<br>* KTP-001 is one time dose intradiscally.<br>|
| Experimental: Cohort 4<br>one time 150 μg/disc dose of KTP-001 by intradiscal injection | Drug: KTP-001<br>* KTP-001 is one time dose intradiscally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Assessed by Adverse Events, Magnetic Resonance Imaging (MRI), X-ray Imaging, Physical Examination, Neurologic Examination and Vital Signs | Any clinically significant changes were recorded as adverse events. They are described in the adverse events section of the results. AEs related to MRI, X-ray Imaging, Physical examination, and Neurologic examination are considered as adverse events of special interest (AESI). A treatment-emergent AE (TEAE) was defined as an AE that was not present prior to treatment with study drug, but appeared following treatment or was present at treatment initiation but worsened in severity during treatment. | 24 months | 
| Number of Participants With Change in 12-lead Electrocardiogram (ECG) and Clinical Laboratory Tests (CLT) | Assessment of the number of participants with change in 12-lead ECG and CLT were assessed from baseline, 24 hours and 13 weeks. | 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Serum Concentrations of KTP-001 Below the Limit of Quantification (BLQ) | The serum concentrations of KTP-001 were below the limit of quantification (BLQ) (<100 ng/mL) at all time points in all participants | 13 weeks | 
| Number of Participants With Anti-KTP-001 Antibody |  | 13 weeks |