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

Phase 1

Completed

Conditions: Lumbar Disc Herniation

Interventions: Drug: KTP-001

Registration Number: NCT01978912

Lead Sponsor: Teijin America, Inc.

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

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 3	KTP-001	one time 50 μg/disc dose of KTP-001 by intradiscal injection
Cohort 4	KTP-001	one time 150 μg/disc dose of KTP-001 by intradiscal injection
Cohort 1	KTP-001	one time 5 μg/disc dose of KTP-001 by intradiscal injection
Cohort 2	KTP-001	one time 15 μg/disc dose of KTP-001 by intradiscal injection

Primary Outcome Measures

Name	Time	Method
Safety Assessed by Adverse Events, Magnetic Resonance Imaging (MRI), X-ray Imaging, Physical Examination, Neurologic Examination and Vital Signs	24 months	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.
Number of Participants With Change in 12-lead Electrocardiogram (ECG) and Clinical Laboratory Tests (CLT)	13 weeks	Assessment of the number of participants with change in 12-lead ECG and CLT were assessed from baseline, 24 hours and 13 weeks.

Secondary Outcome Measures

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

Trial Locations

Locations (10): Emory University
🇺🇸
Atlanta, Georgia, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
Alabama Clinical Therapeutics, LLC
🇺🇸
Birmingham, Alabama, United States
CORE Orthopaedic Medical Center
🇺🇸
Encinitas, California, United States
HOPE Research Institute, LLC
🇺🇸
Phoenix, Arizona, United States
Compass Research, LLC
🇺🇸
Orlando, Florida, United States
Chicago Anesthesia Pain Specialists
🇺🇸
Chicago, Illinois, United States
California Spine Diagnostic
🇺🇸
San Francisco, California, United States
Central Kentucky Research Associates, Inc.
🇺🇸
Lexington, Kentucky, United States
William Beaumont Hospital
🇺🇸
Royal Oak, Michigan, United States