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

• ClinicalTrials.gov Identifier: NCT01124006
• Recruitment Status: Completed
• First Posted: May 14, 2010
• Results First Posted: February 24, 2016
• Last Update Posted: February 24, 2016
• Sponsor: DePuy Spine
• Information provided by (Responsible Party): DePuy Spine

Study Description

Brief Summary:

Study to show the safety and tolerability of Intradiscal rhGDF-5 in subjects with early lumbar disc degeneration

Condition or disease	Intervention/treatment	Phase
Degenerative Disc Disease	Drug: Intradiscal rhGDF-5; Other: Water for injection	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Study Start Date: January 2010
• Actual Primary Completion Date: September 2014
• Actual Study Completion Date: September 2014

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.
Placebo Comparator: Water for injection; Sterile water for injection	Other: Water for injection; Sterile water for injection

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 Definitely Related to Study Drug.
3. Treatment Emergent Adverse Events- Relationship to Study Drug [ Time Frame: 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 Possibly or Probably 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-month ]
   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 Analogue Scale (VAS) at 12 Months From Baseline. [ Time Frame: 12 months ]
   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.
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 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.
2. Oswestry Disability Index (ODI) for low back pain of 30 or greater
3. Low Back Pain score greater than or equal to 4 cm as measured by Visual Analog Scale (VAS) at Visit 1 Baseline

Exclusion Criteria:

1. Persons unable to have a discogram, CT, or MRI
2. Abnormal neurological exam at baseline (e.g., chronic radiculopathy)
3. Active radicular pain due to anatomical compression such as stenosis or disc herniation (radicular pain is defined as pain below the knee)
4. 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)
5. Suspected symptomatic facet joints and/or severe facet joint degeneration at the index level or adjacent segments

Contacts and Locations

Locations

United States, Arizona

Hope Research Institute

Phoenix, Arizona, United States, 85050

United States, California

The 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, Kansas

University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

United States, New York

Hospital for Special Surgery

New York, New York, United States, 10021

United States, Pennsylvania

University Orthopedics Center

State College, Pennsylvania, United States, 16801

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29401

United States, Texas

Spine Team Texas

Southlake, Texas, United States, 76092

Texas Spine & Joint Hospital

Tyler, Texas, United States, 75701

Sponsors and Collaborators

DePuy Spine

More Information

• Responsible Party: DePuy Spine
• ClinicalTrials.gov Identifier: NCT01124006
• Other Study ID Numbers: 09-Intradiscal rhGDF-5-04
• First Posted: May 14, 2010
• Results First Posted: February 24, 2016
• Last Update Posted: February 24, 2016
• Last Verified: January 2016

Additional relevant MeSH terms:

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