Back to resultsA Multicenter, Randomized, Double-blind, Placebo Controlled, Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Effectiveness of 2 Doses of Intradiscal rhGDF-5 (Single Administration) for the Treatment of Early Stage Lumbar Disc Degeneration
Primary Purpose
Degenerative Disc Disease
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Intradiscal rhGDF-5
Water for injection
Sponsored by
About this trial
This is an interventional treatment trial for Degenerative Disc Disease
Eligibility Criteria
Inclusion Criteria:
- Persistent low back pain with at least 3 months of non-surgical therapy at one suspected symptomatic lumbar level (L3/L4 to L5/S1) as confirmed using a standardized provocative discography protocol. The required discography protocol will be provided by the sponsor. Subjects with multilevel disease must have a provocative discogram confirming that only 1 level is symptomatic at least 2 weeks prior to administration. Historical provocative discograms may be used for screening purposes, with an expiry of 12 calendar months from the date performed. If the study treatment is not performed within those 12 calendar months, a new discogram will be required.
- Oswestry Disability Index (ODI) for low back pain of 30 or greater
- Low Back Pain score greater than or equal to 4 cm as measured by Visual Analog Scale (VAS) at Visit 1 Baseline
Exclusion Criteria:
- Persons unable to have a discogram, CT, or MRI
- Abnormal neurological exam at baseline (e.g., chronic radiculopathy)
- Active radicular pain due to anatomical compression such as stenosis or disc herniation (radicular pain is defined as pain below the knee)
- Extravasation of contrast agent during the discogram, into the epidural space (does not include leakage of contrast agent along the needle track or leakage to the outer annular ring at the posterior longitudinal ligament vicinity)
- Suspected symptomatic facet joints and/or severe facet joint degeneration at the index level or adjacent segments
Sites / Locations
- Hope Research Institute
- The Spine Institute
- Durango Orthopedic Associates/Spine Colorado
- Drug Studies America
- University of Kansas Medical Center
- Hospital for Special Surgery
- University Orthopedics Center
- Medical University of South Carolina
- Spine Team Texas
- Texas Spine & Joint Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Intradiscal rhGDF-5
Water for injection
Arm Description
The API is recombinant human growth and differentiation factor-5 (rhGDF-5), a recombinant version of human GDF-5. GDF-5 is a member of the transforming growth factor-b (TGF-b) superfamily and the bone morphogenetic protein (BMP) subfamily, and is known to influence the growth and differentiation of various tissues, including the intervertebral disc. In vitro experiments have shown that rhGDF-5 can stimulate gene expression and synthesis of the extracellular matrix proteins type II collagen and aggrecan. In vivo experiments in rabbit models of disc degeneration have shown that intradiscal injections of rhGDF-5 can stimulate an increase in disc height and hydration.
Sterile water for injection
Outcomes
Primary Outcome Measures
Neurological Assessment for Motor Function and Reflexes/Sensory
Neurological Assessment for Motor Function and Reflexes/Sensory- Number of patients with Clinically Significant Abnormal results at 12 months.
For Motor Function, Clinically Significant Abnormal results are determined by the surgeon investigator and are further classified by grade: 0= No Movement, 1= Flicker/trace of contraction, 2=Active movement when gravity removed, 3= Active movement against gravity, 4= Active Movement against gravity and resistance.
For Reflexes/Sensory, Clinically Significant Abnormal results are determined by the surgeon investigator and are based on exams of the Knee, Ankle, L3-L5 Dermatone, and S1 Dermatome. Tension signs are evaluated with a straight leg raise to determine at which point, if any, sciatic pain occurs.
Treatment Emergent Adverse Events- Relationship to Study Drug
Number of patients with Treatment Emergent Adverse Events that were designated as Definitely Related to Study Drug.
Treatment Emergent Adverse Events- Relationship to Study Drug
Number of patients with Treatment Emergent Adverse Events that were designated as Possibly or Probably Related to Study Drug.
Secondary Outcome Measures
Change in Function Assessed by Oswestry Disability Index Change at 12 Months From Baseline.
The Oswestry Disability Index (ODI) is a 10-category (Pain Intensity, Personal Care, Lifting, Walking, Sitting, Standing, Sleeping, Sex Life, Social Life, Traveling) disability measurement scale with a graded response from 0 to 5, with 0 being the best score (no impairment) to 5 being the worst score (significant impairment). ODI score for a subject is calculated by adding the scores and converting the score to a 100 point scale.
Change in Pain Visual Analogue Scale (VAS) at 12 Months From Baseline.
The Visual Analogue Scale (VAS) pain score asks the subject to place a vertical mark on a horizontal line ( that is approximately 10cm long) with 'No Pain' (score of 0=0cm) listed on the left and 'Very severe pain' (score of 10=10cm) labeled on the right. The subject is instructed to indicate the amount of pain they feel in their back.
Change in Physical Component Summary of Quality of Life Measure Assessed by Short-Form 36 at 12 Months From Baseline.
The 36-item Short Form Health Survey (SF-36) is a patient reported outcome survey that evaluates functional health and well-being. The survey is converted into two summary measures (the Physical Component- PCS and Mental Component- MCS) that are scored from 0 to 100 (where 100 indicates the highest level of health)
Change in Mental Component Summary Quality of Life Measure Assessed by Short Form SF-36 at 12 Months From Baseline.
The 36-item Short Form Health Survey (SF-36) is a patient reported outcome survey that evaluates functional health and well-being. The survey is converted into two summary measures (the Physical Component- PCS and Mental Component- MCS) that are scored from 0 to 100 (where 100 indicates the highest level of health)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01124006
Brief Title
A Multicenter, Randomized, Double-blind, Placebo Controlled, Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Effectiveness of 2 Doses of Intradiscal rhGDF-5 (Single Administration) for the Treatment of Early Stage Lumbar Disc Degeneration
Study Type
Interventional
2. Study Status
Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
September 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
DePuy Spine
4. Oversight
5. Study Description
Brief Summary
Study to show the safety and tolerability of Intradiscal rhGDF-5 in subjects with early lumbar disc degeneration
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Degenerative Disc Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intradiscal rhGDF-5
Arm Type
Experimental
Arm Description
The API is recombinant human growth and differentiation factor-5 (rhGDF-5), a recombinant version of human GDF-5. GDF-5 is a member of the transforming growth factor-b (TGF-b) superfamily and the bone morphogenetic protein (BMP) subfamily, and is known to influence the growth and differentiation of various tissues, including the intervertebral disc. In vitro experiments have shown that rhGDF-5 can stimulate gene expression and synthesis of the extracellular matrix proteins type II collagen and aggrecan. In vivo experiments in rabbit models of disc degeneration have shown that intradiscal injections of rhGDF-5 can stimulate an increase in disc height and hydration.
Arm Title
Water for injection
Arm Type
Placebo Comparator
Arm Description
Sterile water for injection
Intervention Type
Drug
Intervention Name(s)
Intradiscal rhGDF-5
Intervention Description
The API is recombinant human growth and differentiation factor-5 (rhGDF-5), a recombinant version of human GDF-5. GDF-5 is a member of the transforming growth factor-b (TGF-b) superfamily and the bone morphogenetic protein (BMP) subfamily, and is known to influence the growth and differentiation of various tissues, including the intervertebral disc. In vitro experiments have shown that rhGDF-5 can stimulate gene expression and synthesis of the extracellular matrix proteins type II collagen and aggrecan. In vivo experiments in rabbit models of disc degeneration have shown that intradiscal injections of rhGDF-5 can stimulate an increase in disc height and hydration.
Intervention Type
Other
Intervention Name(s)
Water for injection
Intervention Description
Sterile water for injection
Primary Outcome Measure Information:
Title
Neurological Assessment for Motor Function and Reflexes/Sensory
Description
Neurological Assessment for Motor Function and Reflexes/Sensory- Number of patients with Clinically Significant Abnormal results at 12 months.
For Motor Function, Clinically Significant Abnormal results are determined by the surgeon investigator and are further classified by grade: 0= No Movement, 1= Flicker/trace of contraction, 2=Active movement when gravity removed, 3= Active movement against gravity, 4= Active Movement against gravity and resistance.
For Reflexes/Sensory, Clinically Significant Abnormal results are determined by the surgeon investigator and are based on exams of the Knee, Ankle, L3-L5 Dermatone, and S1 Dermatome. Tension signs are evaluated with a straight leg raise to determine at which point, if any, sciatic pain occurs.
Time Frame
12 months
Title
Treatment Emergent Adverse Events- Relationship to Study Drug
Description
Number of patients with Treatment Emergent Adverse Events that were designated as Definitely Related to Study Drug.
Time Frame
Through a 12 month period and annual telephone contact at 24 and 36 months for subject health status follow-up.
Title
Treatment Emergent Adverse Events- Relationship to Study Drug
Description
Number of patients with Treatment Emergent Adverse Events that were designated as Possibly or Probably Related to Study Drug.
Time Frame
12 month period and annual telephone contact at 24 and 36 months for subject health status follow-up
Secondary Outcome Measure Information:
Title
Change in Function Assessed by Oswestry Disability Index Change at 12 Months From Baseline.
Description
The Oswestry Disability Index (ODI) is a 10-category (Pain Intensity, Personal Care, Lifting, Walking, Sitting, Standing, Sleeping, Sex Life, Social Life, Traveling) disability measurement scale with a graded response from 0 to 5, with 0 being the best score (no impairment) to 5 being the worst score (significant impairment). ODI score for a subject is calculated by adding the scores and converting the score to a 100 point scale.
Time Frame
12-month
Title
Change in Pain Visual Analogue Scale (VAS) at 12 Months From Baseline.
Description
The Visual Analogue Scale (VAS) pain score asks the subject to place a vertical mark on a horizontal line ( that is approximately 10cm long) with 'No Pain' (score of 0=0cm) listed on the left and 'Very severe pain' (score of 10=10cm) labeled on the right. The subject is instructed to indicate the amount of pain they feel in their back.
Time Frame
12 months
Title
Change in Physical Component Summary of Quality of Life Measure Assessed by Short-Form 36 at 12 Months From Baseline.
Description
The 36-item Short Form Health Survey (SF-36) is a patient reported outcome survey that evaluates functional health and well-being. The survey is converted into two summary measures (the Physical Component- PCS and Mental Component- MCS) that are scored from 0 to 100 (where 100 indicates the highest level of health)
Time Frame
12 months
Title
Change in Mental Component Summary Quality of Life Measure Assessed by Short Form SF-36 at 12 Months From Baseline.
Description
The 36-item Short Form Health Survey (SF-36) is a patient reported outcome survey that evaluates functional health and well-being. The survey is converted into two summary measures (the Physical Component- PCS and Mental Component- MCS) that are scored from 0 to 100 (where 100 indicates the highest level of health)
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Persistent low back pain with at least 3 months of non-surgical therapy at one suspected symptomatic lumbar level (L3/L4 to L5/S1) as confirmed using a standardized provocative discography protocol. The required discography protocol will be provided by the sponsor. Subjects with multilevel disease must have a provocative discogram confirming that only 1 level is symptomatic at least 2 weeks prior to administration. Historical provocative discograms may be used for screening purposes, with an expiry of 12 calendar months from the date performed. If the study treatment is not performed within those 12 calendar months, a new discogram will be required.
Oswestry Disability Index (ODI) for low back pain of 30 or greater
Low Back Pain score greater than or equal to 4 cm as measured by Visual Analog Scale (VAS) at Visit 1 Baseline
Exclusion Criteria:
Persons unable to have a discogram, CT, or MRI
Abnormal neurological exam at baseline (e.g., chronic radiculopathy)
Active radicular pain due to anatomical compression such as stenosis or disc herniation (radicular pain is defined as pain below the knee)
Extravasation of contrast agent during the discogram, into the epidural space (does not include leakage of contrast agent along the needle track or leakage to the outer annular ring at the posterior longitudinal ligament vicinity)
Suspected symptomatic facet joints and/or severe facet joint degeneration at the index level or adjacent segments
Facility Information:
Facility Name
Hope Research Institute
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85050
Country
United States
Facility Name
The Spine Institute
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Durango Orthopedic Associates/Spine Colorado
City
Durango
State/Province
Colorado
ZIP/Postal Code
81301
Country
United States
Facility Name
Drug Studies America
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30060
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Hospital for Special Surgery
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
University Orthopedics Center
City
State College
State/Province
Pennsylvania
ZIP/Postal Code
16801
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29401
Country
United States
Facility Name
Spine Team Texas
City
Southlake
State/Province
Texas
ZIP/Postal Code
76092
Country
United States
Facility Name
Texas Spine & Joint Hospital
City
Tyler
State/Province
Texas
ZIP/Postal Code
75701
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Multicenter, Randomized, Double-blind, Placebo Controlled, Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Effectiveness of 2 Doses of Intradiscal rhGDF-5 (Single Administration) for the Treatment of Early Stage Lumbar Disc Degeneration
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