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

NCT01182337 | Completed Phase 1 Results

• 1 other identifier: 09-Intradiscal rhGDF-5-03
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 7

Brief Summary

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

Conditions

Early Lumbar Disc Degeneration

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 Analog 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

Vehicle control

PLACEBO COMPARATOR

Excipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection

Drug: Vehicle control

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

Vehicle control DRUG

Excipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection

Vehicle control

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 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, with an expiry of 12 months from the date performed.
• 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
• Male or Female 18 years of age or older

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
• Janssen Korea, Ltd., Korea: collaborator

Study Sites (7)

Yeungnam University Medical Center

Daegu, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Gangnam Severance Hospital

Seoul, South Korea

Location

Korea University Anam Hospital

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Seoul St. Mary Hospital

Seoul, South Korea

Location

Yonsei University Health System

Seoul, South Korea

Location

Related Publications (1)

• Adoungotchodo A, Epure LM, Mwale F, Lerouge S. Chitosan-based hydrogels supplemented with gelatine and Link N enhance extracellular matrix deposition by encapsulated cells in a degenerative intervertebral disc environment. Eur Cell Mater. 2021 May 4;41:471-484. doi: 10.22203/eCM.v041a30.

  PMID: 33945627 DERIVED

MeSH Terms

Conditions

Intervertebral Disc Degeneration

Condition Hierarchy (Ancestors)

Spinal Diseases; Bone Diseases; Musculoskeletal Diseases

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 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2010
• First Posted: August 16, 2010
• Study Start: June 1, 2010
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: February 26, 2016
• Results First Posted: January 27, 2016

Record last verified: 2016-01

Locations

KR (7)