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

Primary Purpose

Lumbar Disc Herniation

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
KTP-001
Sponsored by
Teijin America, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lumbar Disc Herniation

Eligibility Criteria

30 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Alabama Clinical Therapeutics, LLC
  • HOPE Research Institute, LLC
  • CORE Orthopaedic Medical Center
  • California Spine Diagnostic
  • Compass Research, LLC
  • Emory University
  • Rush University Medical Center
  • Chicago Anesthesia Pain Specialists
  • Central Kentucky Research Associates, Inc.
  • William Beaumont Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Cohort 4

Arm Description

one time 5 μg/disc dose of KTP-001 by intradiscal injection

one time 15 μg/disc dose of KTP-001 by intradiscal injection

one time 50 μg/disc dose of KTP-001 by intradiscal injection

one time 150 μg/disc dose of KTP-001 by intradiscal injection

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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
Number of Participants With Anti-KTP-001 Antibody

Full Information

First Posted
October 22, 2013
Last Updated
February 2, 2020
Sponsor
Teijin America, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01978912
Brief Title
A Study to Evaluate Safety and Exploratory Efficacy of KTP-001 in Subjects With Lumbar Disc Herniation
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
February 2013 (undefined)
Primary Completion Date
October 16, 2018 (Actual)
Study Completion Date
October 16, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Teijin America, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lumbar Disc Herniation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
one time 5 μg/disc dose of KTP-001 by intradiscal injection
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
one time 15 μg/disc dose of KTP-001 by intradiscal injection
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
one time 50 μg/disc dose of KTP-001 by intradiscal injection
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
one time 150 μg/disc dose of KTP-001 by intradiscal injection
Intervention Type
Drug
Intervention Name(s)
KTP-001
Intervention Description
KTP-001 is one time dose intradiscally.
Primary Outcome Measure Information:
Title
Safety Assessed by Adverse Events, Magnetic Resonance Imaging (MRI), X-ray Imaging, Physical Examination, Neurologic Examination and Vital Signs
Description
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.
Time Frame
24 months
Title
Number of Participants With Change in 12-lead Electrocardiogram (ECG) and Clinical Laboratory Tests (CLT)
Description
Assessment of the number of participants with change in 12-lead ECG and CLT were assessed from baseline, 24 hours and 13 weeks.
Time Frame
13 weeks
Secondary Outcome Measure Information:
Title
Number of Participants Serum Concentrations of KTP-001 Below the Limit of Quantification (BLQ)
Description
The serum concentrations of KTP-001 were below the limit of quantification (BLQ) (<100 ng/mL) at all time points in all participants
Time Frame
13 weeks
Title
Number of Participants With Anti-KTP-001 Antibody
Time Frame
13 weeks
Other Pre-specified Outcome Measures:
Title
Changes in Lower Back Pain or Leg Pain Assessed by 11-point Numerical Rating Scale
Description
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.
Time Frame
Baseline, 6 weeks and 13 weeks post-dose
Title
Number of Participants With Changes to Spinal Flexion and Tension Using the Straight-Leg Rising and/or Femoral Stretch Test
Description
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.
Time Frame
Baseline, 6 weeks and 13 weeks post-dose
Title
Number of Participants With Changes in the Oswestry Disability Index
Description
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;
Time Frame
Baseline, 6 weeks and 13 weeks post-dose
Title
Changes in Quality of Life as Assessed by Short Form-12 (SF-12)
Description
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.
Time Frame
Baseline, 6 weeks and 13 weeks post-dose
Title
Patient Global Impression of Change (PGI-C)
Description
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.
Time Frame
Baseline, 6 weeks and 13 weeks post-dose
Title
Changes in Serum Concentrations of Keratan Sulfate
Description
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.
Time Frame
Baseline, 6 and 24 hours and 1, 2, 4, 6 weeks and 13 weeks post-dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Alabama Clinical Therapeutics, LLC
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35235
Country
United States
Facility Name
HOPE Research Institute, LLC
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85018
Country
United States
Facility Name
CORE Orthopaedic Medical Center
City
Encinitas
State/Province
California
ZIP/Postal Code
92024
Country
United States
Facility Name
California Spine Diagnostic
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Compass Research, LLC
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Chicago Anesthesia Pain Specialists
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60657
Country
United States
Facility Name
Central Kentucky Research Associates, Inc.
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40509
Country
United States
Facility Name
William Beaumont Hospital
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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