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A Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Effectiveness of Single Administration Intradiscal rhGDF-5 for the Treatment of Early Stage Lumbar Disc Degeneration

This study has been completed.
Sponsor:
Collaborator:
Janssen-Cilag Pty Ltd
Information provided by (Responsible Party):
DePuy Spine
ClinicalTrials.gov Identifier:
NCT01158924
First received: July 1, 2010
Last updated: January 26, 2016
Last verified: January 2016
  Purpose
Study to show the safety, tolerability and preliminary effectiveness of Intradiscal rhGDF-5 in subjects with early lumbar disc degeneration.

Condition Intervention Phase
Early Lumbar Disc Degeneration
Drug: Intradiscal rhGDF-5
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: A Phase I/IIa, Multicenter, Open-label, Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Effectiveness of Single Administration Intradiscal rhGDF-5 for the Treatment of Early Stage Lumbar Disc Degeneration

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 related or possibly related to Study Drug.


Secondary Outcome Measures:
  • Change in Function Assessed by Oswestry Disability Index Change at 12 Months From Baseline [ Time Frame: 12 months ] [ 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 Analog Scale (VAS) at 12 Months From Baseline. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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. [ 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: 40
Study Start Date: March 2010
Study Completion Date: March 2014
Primary Completion Date: March 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.

  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 or two suspected symptomatic lumbar levels (L3/L4 to L5/S1)

    a. The recruiting physician will use their standard clinical and radiological practice to determine the one/two disc level(s) be treated, i.e., but not limited to a combination of MRI, CT and/or Technetium bone scans, functional x-rays, input from a spinal injection program (targeting facet joints and/or epidural space) and discography (a discogram performed within 12 months of the anticipated study treatment date is acceptable, as long as the subject has not had an accident or re-injury).

  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
  4. Male or Female 18 years of age or older

Exclusion Criteria:

  1. Persons unable to have an MRI
  2. Abnormal neurological exam at baseline (e.g., chronic radiculopathy)
  3. Persons with neurological or radiographic evidence of active radicular pain due to anatomical compression such as stenosis or disc herniation (persons with somatic referred pain are allowed)
  4. Suspected symptomatic facet joints and/or severe facet joint degeneration at the index level(s) or adjacent segments
  5. Suspected symptomatic sacro-iliac joint
  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: NCT01158924

Locations
Australia, New South Wales
Hunter Clinical Research
Broadmeadow, New South Wales, Australia, 2292
St. George Private Hospital
Kogarah, New South Wales, Australia, 2217
Australia, Queensland
BrizBain & Spine, The Wesley Hospital
Auchenflower, Queensland, Australia, 4066
Sponsors and Collaborators
DePuy Spine
Janssen-Cilag Pty Ltd
  More Information

Responsible Party: DePuy Spine
ClinicalTrials.gov Identifier: NCT01158924     History of Changes
Other Study ID Numbers: 09-Intradiscal rhGDF-5-02 
Study First Received: July 1, 2010
Results First Received: December 18, 2015
Last Updated: January 26, 2016
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

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

ClinicalTrials.gov processed this record on September 23, 2016