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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
DePuy Spine
ClinicalTrials.gov Identifier:
NCT01124006
First received: May 11, 2010
Last updated: January 26, 2016
Last verified: January 2016
  Purpose
Study to show the safety and tolerability of Intradiscal rhGDF-5 in subjects with early lumbar disc degeneration

Condition Intervention Phase
Degenerative Disc Disease
Drug: Intradiscal rhGDF-5
Other: Water for injection
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by DePuy Spine:

Primary Outcome Measures:
  • Neurological Assessment for Motor Function and Reflexes/Sensory [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: Through a 12 month period and annual telephone contact at 24 and 36 months for subject health status follow-up. ] [ Designated as safety issue: Yes ]
    Number of patients with Treatment Emergent Adverse Events that were designated as Definitely Related to Study Drug.

  • 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 ] [ Designated as safety issue: Yes ]
    Number of patients with Treatment Emergent Adverse Events that were designated as Possibly or Probably Related to Study Drug.


Secondary Outcome Measures:
  • Change in Function Assessed by Oswestry Disability Index Change at 12 Months From Baseline. [ Time Frame: 12-month ] [ Designated as safety issue: No ]
    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 Analogue Scale (VAS) at 12 Months From Baseline. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.

  • Change in Physical Component Summary of Quality of Life Measure Assessed by Short-Form 36 at 12 Months From Baseline. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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)


Enrollment: 24
Study Start Date: January 2010
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01124006

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     History of Changes
Other Study ID Numbers: 09-Intradiscal rhGDF-5-04 
Study First Received: May 11, 2010
Results First Received: December 18, 2015
Last Updated: January 26, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Intervertebral Disc Degeneration
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases

ClinicalTrials.gov processed this record on August 28, 2016