Clinical trial NCT01978912: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lumbar Disc Herniation
Lead sponsor: Teijin America, Inc.
Sponsor class: INDUSTRY
First posted: 2013-11-08
Enrollment: 24
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Safety Assessed by Adverse Events, Magnetic Resonance Imaging (MRI), X-ray Imaging, Physical Examination, Neurologic Examination and Vital Signs
timeFrame: 24 months
measure: Number of Participants With Change in 12-lead Electrocardiogram (ECG) and Clinical Laboratory Tests (CLT)
timeFrame: 13 weeks
Secondary outcomes:
measure: Number of Participants Serum Concentrations of KTP-001 Below the Limit of Quantification (BLQ)
timeFrame: 13 weeks
measure: Number of Participants With Anti-KTP-001 Antibody
timeFrame: 13 weeks
Other outcomes:
measure: Changes in Lower Back Pain or Leg Pain Assessed by 11-point Numerical Rating Scale
timeFrame: Baseline, 6 weeks and 13 weeks post-dose
measure: Number of Participants With Changes to Spinal Flexion and Tension Using the Straight-Leg Rising and/or Femoral Stretch Test
timeFrame: Baseline, 6 weeks and 13 weeks post-dose
measure: Number of Participants With Changes in the Oswestry Disability Index
timeFrame: Baseline, 6 weeks and 13 weeks post-dose
measure: Changes in Quality of Life as Assessed by Short Form-12 (SF-12)
timeFrame: Baseline, 6 weeks and 13 weeks post-dose
measure: Patient Global Impression of Change (PGI-C)
timeFrame: Baseline, 6 weeks and 13 weeks post-dose
measure: Changes in Serum Concentrations of Keratan Sulfate
timeFrame: Baseline, 6 and 24 hours and 1, 2, 4, 6 weeks and 13 weeks post-dose
Locations:
city: Birmingham
country: United States
facility: Alabama Clinical Therapeutics, LLC
state: Alabama
city: Phoenix
country: United States
facility: HOPE Research Institute, LLC
state: Arizona
city: Encinitas
country: United States
facility: CORE Orthopaedic Medical Center
state: California
city: San Francisco
country: United States
facility: California Spine Diagnostic
state: California
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: Chicago Anesthesia Pain Specialists
state: Illinois
city: Lexington
country: United States
facility: Central Kentucky Research Associates, Inc.
state: Kentucky
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
Study officials:
References: