Intradiscal rhGDF-5 Phase I/II Clinical Trial

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Intradiscal rhGDF-5

About this trial

This is an interventional treatment trial for Degenerative Disc Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intradiscal rhGDF-5

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.

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 related or possibly 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 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.

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

NCT ID

NCT00813813

First Posted

December 22, 2008

Last Updated

January 26, 2016

Sponsor

DePuy Spine

1. Study Identification

Unique Protocol Identification Number

NCT00813813

Brief Title

Intradiscal rhGDF-5 Phase I/II Clinical Trial

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2016

Overall Recruitment Status

Completed

Study Start Date

June 2008 (undefined)

Primary Completion Date

June 2013 (Actual)

Study Completion Date

June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

DePuy Spine

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

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 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

32 (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.

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.

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 related or possibly 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

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 months

Title

Change in Pain Visual Analog Scale (VAS) at 12 Months From Baseline

Description

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.

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 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

Overall Study Officials: