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

NCT01124006 | Completed Phase 2 Results

• 1 other identifier: 09-Intradiscal rhGDF-5-04
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 10

Brief Summary

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

Conditions

Degenerative Disc Disease

Outcome Measures

Primary Outcomes (3)

• 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 Definitely Related to Study Drug.

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

• Treatment Emergent Adverse Events- Relationship to Study Drug

  Number of patients with Treatment Emergent Adverse Events that were designated as Possibly or Probably Related to Study Drug.

  12 month period and annual telephone contact at 24 and 36 months for subject health status follow-up

Secondary Outcomes (4)

• Change in Function Assessed by Oswestry Disability Index Change at 12 Months From Baseline.

  12-month

• Change in Pain Visual Analogue Scale (VAS) at 12 Months From Baseline.

  12 months

• Change in Physical Component Summary of Quality of Life Measure Assessed by Short-Form 36 at 12 Months From Baseline.

  12 months

• Change in Mental Component Summary Quality of Life Measure Assessed by Short Form SF-36 at 12 Months From Baseline.

  12 months

Study Arms (2)

Intradiscal rhGDF-5

EXPERIMENTAL

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

Water for injection

PLACEBO COMPARATOR

Sterile water for injection

Other: Water for injection

Interventions

Intradiscal rhGDF-5 DRUG

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.

Intradiscal rhGDF-5

Water for injection OTHER

Sterile water for injection

Water for injection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Oswestry Disability Index (ODI) for low back pain of 30 or greater
• Low Back Pain score greater than or equal to 4 cm as measured by Visual Analog Scale (VAS) at Visit 1 Baseline

You may not qualify if:

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

Sponsors & Collaborators

• DePuy Spine: lead

Study Sites (10)

Hope Research Institute

Phoenix, Arizona, 85050, United States

Location

The Spine Institute

Santa Monica, California, 90404, United States

Location

Durango Orthopedic Associates/Spine Colorado

Durango, Colorado, 81301, United States

Location

Drug Studies America

Marietta, Georgia, 30060, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

University Orthopedics Center

State College, Pennsylvania, 16801, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29401, United States

Location

Spine Team Texas

Southlake, Texas, 76092, United States

Location

Texas Spine & Joint Hospital

Tyler, Texas, 75701, United States

Location

MeSH Terms

Conditions

Intervertebral Disc Degeneration

Interventions

Water; Injections

Condition Hierarchy (Ancestors)

Spinal Diseases; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Mark Lotito
• Organization: DePuy Synthes Spine

Mlotito@its.jnj.com

508-880-8045

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2010
• First Posted: May 14, 2010
• Study Start: January 1, 2010
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: February 24, 2016
• Results First Posted: February 24, 2016

Record last verified: 2016-01

Locations

US (10)