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

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

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

Study Overview

• Status: Completed
• Conditions: Lumbar Disc Herniation
• Intervention / Treatment: Drug: KTP-001

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
      • Alabama Clinical Therapeutics, LLC
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • HOPE Research Institute, LLC
  • California
    • Encinitas, California, United States, 92024
      • CORE Orthopaedic Medical Center
    • San Francisco, California, United States, 94115
      • California Spine Diagnostic
  • Florida
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60657
      • Chicago Anesthesia Pain Specialists
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Central Kentucky Research Associates, Inc.
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Lower Back Pain or Leg Pain Assessed by 11-point Numerical Rating Scale	Lower back and leg pain were assessed using an 11-point numerical rating scale (0 = "no pain" and 10 = "worst possible pain"). The endpoint was mean change from baseline at 6 and 13 weeks post-dose; with a negative number suggesting an improvement in pain while a positive number suggests a worsening in pain.	Baseline, 6 weeks and 13 weeks post-dose
Number of Participants With Changes to Spinal Flexion and Tension Using the Straight-Leg Rising and/or Femoral Stretch Test	The changes to spinal flexion and tension were assessed using Straight-Leg Rising (SLR) and Femoral Stretch (FS) tests which are on a scale of no change, positive to negative or negative to positive and where a positive result for SLR may indicate between 30 and 70 degrees, where a positive result for FS may indicate pain in the anterior thigh of the test leg and the elicited pain.	Baseline, 6 weeks and 13 weeks post-dose
Number of Participants With Changes in the Oswestry Disability Index	The Oswestry Disability Index (ODI) score is calculated as participant score divided by possible score multiplied by 100, where the following scores can be interpreted to indicate: 0-20% = Minimal disability; 20-40% = Moderate disability; 40-60% = Severe disability; 60-80% = Crippled; 80-100% = Bed bound;	Baseline, 6 weeks and 13 weeks post-dose
Changes in Quality of Life as Assessed by Short Form-12 (SF-12)	The endpoint was change from baseline at Week 6 and 13 hours post-dose. The Short Form-12 (SF-12) is a Quality of Life questionnaire which measures functional health and well-being from a participant's perspective across eight health domains. Each participant answers questions on a 5-point Likert scale, which rates responses according to how much the participant agrees or disagrees with a particular statement on their health and wellbeing, including vitality/physical functioning/bodily pain/general health perceptions/physical role functioning/emotional role functioning/social role functioning and mental health. Each scale is transformed into a 0-100 scale, assuming each question carries equal weight. Lower scores mean greater disability and higher scores mean less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.	Baseline, 6 weeks and 13 weeks post-dose
Patient Global Impression of Change (PGI-C)	The Patient Global Impression Change PGI-C scale was used where the scale ranges are from 1 (no change or condition has got worse) to 7 (a great deal better, and a considerable improvement). The endpoint was the value at 6 and 13 weeks post-dose.	Baseline, 6 weeks and 13 weeks post-dose
Changes in Serum Concentrations of Keratan Sulfate	The endpoint was change from baseline at 6 and 24 hours post-dose, and at the 1-, 2-, 4-, 6-, and 13-week follow-up visits or early termination visit.	Baseline, 6 and 24 hours and 1, 2, 4, 6 weeks and 13 weeks post-dose

Collaborators and Investigators

• Sponsor: Teijin America, Inc.

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): October 16, 2018
• Study Completion (Actual): October 16, 2018

Study Registration Dates

• First Submitted: October 22, 2013
• First Submitted That Met QC Criteria: November 1, 2013
• First Posted (Estimate): November 8, 2013

Study Record Updates

• Last Update Posted (Actual): February 11, 2020
• Last Update Submitted That Met QC Criteria: February 2, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Pathological Conditions, Anatomical; Spinal Diseases; Bone Diseases; Hernia; Intervertebral Disc Displacement
• Other Study ID Numbers: KTP-001-CL-101