Intradiscal rhGDF-5 Phase I/II Clinical Trial

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 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

Study Overview

• Status: Completed
• Conditions: Degenerative Disc Disease
• Intervention / Treatment: Drug: Intradiscal rhGDF-5

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90404
      • Spine Institute
  • Colorado
    • Durango, Colorado, United States, 81301
      • Durango Orthopedic Associates/Spine Colorado
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Drug Studies America
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Rehabilitation Institute of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Riverhills Healthcare, Inc.
  • Texas
    • Plano, Texas, United States, 75093
      • TBI Clinical Research, LLC
  • Virginia
    • Richmond, Virginia, United States, 23235
      • Virginia Commonwealth University Spine Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 months
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.	Through a 12 month period and annual telephone contact at 24 and 36 months for subject health status follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 months
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.	12 months
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).	12 Months
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).	12 Months

Collaborators and Investigators

• Sponsor: DePuy Spine
• Investigators: Principal Investigator: James Rathmell, MD, Massachusetts General Hospital; Principal Investigator: Marvin Tark, MD, Drug Study America; Principal Investigator: Jim Youssef, MD, Durango Orthopedic Associates/Spine Colorado; Principal Investigator: Jonathan Borden, MD, Riverhills Healthcare, Inc.; Principal Investigator: Yaoming Gu, MD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (ACTUAL): June 1, 2013
• Study Completion (ACTUAL): June 1, 2013

Study Registration Dates

• First Submitted: December 22, 2008
• First Submitted That Met QC Criteria: December 22, 2008
• First Posted (ESTIMATE): December 23, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): February 26, 2016
• Last Update Submitted That Met QC Criteria: January 26, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Spinal Diseases; Bone Diseases; Intervertebral Disc Degeneration
• Other Study ID Numbers: 07-Intradiscal rhGDF-5-01