A Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Effectiveness of Single Administration Intradiscal rhGDF-5 for the Treatment of Early Stage Lumbar Disc Degeneration

Study Overview
=================
Brief Summary
-----------------
Study to show the safety, tolerability and preliminary effectiveness of Intradiscal rhGDF-5 in subjects with early lumbar disc degeneration

Official Title
-----------------
A Multicenter, Randomized, Double-blind, Placebo Controlled, Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Effectiveness of Single Administration Intradiscal rhGDF-5 for the Treatment of Early Stage Lumbar Disc Degeneration

Conditions
-----------------
Early Lumbar Disc Degeneration

Intervention / Treatment
-----------------
* Drug: Intradiscal rhGDF-5
* Drug: Vehicle control


Participation Criteria
=================
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 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, with an expiry of 12 months from the date performed. 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 Male or Female 18 years of age or older 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intradiscal rhGDF-5<br>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. | Drug: Intradiscal rhGDF-5<br>* 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.<br>|
| Placebo Comparator: Vehicle control<br>Excipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection | Drug: Vehicle control<br>* Excipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12 months | 
| 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. | Through a 12 month period and annual telephone contact at 24 and 36 months for subject health status follow-up | 
| 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. | 12 month period and annual telephone contact at 24 and 36 months for subject health status follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12 month | 
| Change in Pain Visual Analog Scale (VAS) at 12 Months From Baseline. | The Visual Analog Scale (VAS) pain score asks the subject to place a vertical mark on a horizontal line (that is approximately 10 cm long) with 'No Pain' (score of 0 = 0 cm) 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. | 12 months | 
| 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). | 12 months | 
| 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). | 12 Months |