Intradiscal rhGDF-5 Phase I/II Clinical Trial

• ClinicalTrials.gov Identifier: NCT00813813
• Recruitment Status: Completed
• First Posted: December 23, 2008
• Results First Posted: January 27, 2016
• Last Update Posted: February 26, 2016
• Sponsor: DePuy Spine
• Information provided by (Responsible Party): DePuy Spine

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

Condition or disease	Intervention/treatment	Phase
Degenerative Disc Disease	Drug: Intradiscal rhGDF-5	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: June 2008
• Actual Primary Completion Date: June 2013
• Actual Study Completion Date: June 2013

Arms and Interventions

Arm

Intervention/treatment

Experimental: Intradiscal rhGDF-5; 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; 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.

Outcome Measures

Primary Outcome Measures :

1. Neurological Assessment for Motor Function and Reflexes/Sensory [ Time Frame: 12 months ]

   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.

2. Treatment Emergent Adverse Events- Relationship 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 ]
   Number of patients with Treatment Emergent Adverse Events that were designated as related or possibly related to Study Drug.

Secondary Outcome Measures :

1. Change in Function Assessed by Oswestry Disability Index Change at 12 Months From Baseline [ Time Frame: 12 months ]
   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.
2. Change in Pain Visual Analog Scale (VAS) at 12 Months From Baseline [ Time Frame: 12 months ]
   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.
3. Change in Physical Component Summary of Quality of Life Measure Assessed by Short-Form 36 at 12 Months From Baseline [ Time Frame: 12 Months ]
   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).
4. Change in Mental Component Summary Quality of Life Measure Assessed by Short Form SF-36 at 12 Months From Baseline [ Time Frame: 12 Months ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. 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
2. Oswestry Disability Index of 30 or greater
3. 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:

1. Persons unable to have a discogram, CT or an MRI
2. Abnormal neurological exam at baseline (e.g., radiculopathy)
3. Radicular pain
4. Leak of contrast agent during the discogram, into the epidural space (does not include leak of contrast agent along the needle track)
5. 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

Contacts and Locations

Locations

United States, California

Spine Institute

Santa Monica, California, United States, 90404

United States, Colorado

Durango Orthopedic Associates/Spine Colorado

Durango, Colorado, United States, 81301

United States, Georgia

Drug Studies America

Marietta, Georgia, United States, 30060

United States, Illinois

Rehabilitation Institute of Chicago

Chicago, Illinois, United States, 60611

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, Ohio

Riverhills Healthcare, Inc.

Cincinnati, Ohio, United States, 45242

United States, Texas

TBI Clinical Research, LLC

Plano, Texas, United States, 75093

United States, Virginia

Virginia Commonwealth University Spine Center

Richmond, Virginia, United States, 23235

Sponsors and Collaborators

DePuy Spine

Investigators

• Principal Investigator: James Rathmell, MD; Massachusetts General Hospital
• Principal Investigator: Richard Guyer, MD; Texas Back Institute
• Principal Investigator: Marvin Tark, MD; Drug Study America
• Principal Investigator: Jim Youssef, MD; Durango Orthopedic Associates/Spine Colorado
• Principal Investigator: Norman Harden, MD; Shirley Ryan AbilityLab
• Principal Investigator: Jonathan Borden, MD; Riverhills Healthcare, Inc.
• Principal Investigator: Yaoming Gu, MD; Virginia Commonwealth University

More Information

• Responsible Party: DePuy Spine
• ClinicalTrials.gov Identifier: NCT00813813
• Other Study ID Numbers: 07-Intradiscal rhGDF-5-01
• First Posted: December 23, 2008
• Results First Posted: January 27, 2016
• Last Update Posted: February 26, 2016
• Last Verified: January 2016

Additional relevant MeSH terms:

Intervertebral Disc Degeneration; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases