Intradiscal rhGDF-5 Phase I/II Clinical Trial

Study Overview
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Brief Summary
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Study to show the effectiveness and safety of a single injection of rhGDF5 into a degenerating single spinal disc in treating lumbar level degenerative disc disease

Official Title
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Phase I/II, Multicenter, Open-label, Single Administration, Dose Finding, Clinical Trial to Evaluate the Safety and Tolerability of Intradiscal rhGDF-5 for the Treatment of Early Stage Lumbar Disc Degeneration

Conditions
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Degenerative Disc Disease

Intervention / Treatment
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* Drug: Intradiscal rhGDF-5


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Persistent low back pain, with at least 3 months of non-surgical therapy, at one symptomatic lumbar level (L3/L4 to L5/S1) as confirmed using a standardized discography protocol Oswestry Disability Index of 30 or greater Low back pain score greater than or equal to 4 cm as measured by VAS, at Visit 1 baseline and on day of treatment to confirm eligibility prior to administration Exclusion Criteria: Persons unable to have a discogram, CT or an MRI Abnormal neurological exam at baseline (e.g., radiculopathy) Radicular pain Leak of contrast agent during the discogram, into the epidural space (does not include leak of contrast agent along the needle track) MRI findings demonstrate any of the following:· Suspected disc appears normal· >50% decrease in disc height· Modic changes, and/or· Presence of osteophytes or significant facet arthrosis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


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>|

What is the study measuring?
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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 related or possibly related to Study Drug. | Through a 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 months | 
| 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 |