Early Lumbar Disc DegenerationPhase 1/2NCT01182337

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

A Phase 1/2 study testing Intradiscal rhGDF-5 in people with Early Lumbar Disc Degeneration, run by DePuy Spine at 7 sites in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

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

Who is it for?: Ages 18 years and older
Conditions the study is for: Early Lumbar Disc Degeneration
What is being tested?: Intradiscal rhGDF-5
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 31 participants
Where: 7 sitesSouth Korea
Study dates: Jun 2010to Jun 2014
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

South Korea7 sites

Yeungnam University Medical Center
Daegu
Asan Medical Center
Seoul
Gangnam Severance Hospital
Seoul
Korea University Anam Hospital
Seoul
Seoul National University Hospital
Seoul
Seoul St. Mary Hospital
Seoul
Yonsei University Health System
Seoul

Other trials in South Korea

About this study

Official title: A Multicenter, Randomized, Double-blind, Placebo Controlled, 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

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
Being tested: Intradiscal rhGDF-5, Vehicle control
Medical subject headings: Intervertebral Disc Degeneration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT01182337
Study group	Role	What they receive
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. Receives: Drug: Intradiscal rhGDF-5
Vehicle control	Placebo comparator	Excipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection Receives: Drug: Vehicle control

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
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.
Measured: 12 month
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.
Measured: 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).
Measured: 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).
Measured: 12 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2010Jun 2014

First posted16 Aug 2010 (estimated)
Study startJun 2010
Primary completionJun 2014
Study completionJun 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Early Lumbar Disc DegenerationStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01182337
Sponsor's protocol ID: 09-Intradiscal rhGDF-5-03
Status last verified: Jan 2016
First submitted: 11 Aug 2010
Last updated: 26 Feb 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 33945627

Study at a glance

From the registry record, last updated by the sponsor on 26 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Randomized, Double-blind, Placebo Controlled, 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
ClinicalTrials.gov ID: NCT01182337
Acronym / sponsor ID: 09-Intradiscal rhGDF-5-03
Conditions: Early Lumbar Disc Degeneration
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 31 participants (actual)
Lead sponsor: DePuy SpineIndustry (pharma, biotech, devices)
Collaborators: Janssen Korea, Ltd., Korea
Study start: Jun 2010
Primary completion: Jun 2014 (actual)
Study completion: Jun 2014 (actual)
First posted: 16 Aug 2010 (estimated)
Results: Posted 27 Jan 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Intradiscal rhGDF-5	Experimental	Drug: Intradiscal rhGDF-5The 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.
Vehicle control	Placebo comparator	Drug: Vehicle controlExcipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Intradiscal rhGDF-5The 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 controlExcipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection	Drug	Vehicle control

Primary outcome

Neurological Assessment for Motor Function and Reflexes/Sensory
Time frame: 12 months
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
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
Number of patients with Treatment Emergent Adverse Events that were designated as Possibly or Probably Related to Study Drug.

4 secondary outcomes

Change in Function Assessed by Oswestry Disability Index Change at 12 Months From Baseline.
Time frame: 12 month
Change in Pain Visual Analog Scale (VAS) at 12 Months From Baseline.
Time frame: 12 months
Change in Physical Component Summary of Quality of Life Measure Assessed by Short Form 36 at 12 Months From Baseline
Time frame: 12 months
Change in Mental Component Summary Quality of Life Measure Assessed by Short Form SF-36 at 12 Months From Baseline.
Time frame: 12 Months

Results and safety

Results posted to the registry on 27 Jan 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Intradiscal rhGDF-5 1.0mg	22	19
Vehicle Control	9	7

Primary outcome: Neurological Assessment for Motor Function and Reflexes/Sensory

Time frame: 12 months. Number. Unit: participants

Measure	Intradiscal rhGDF-5 1.0mg n = 21	Vehicle Control n = 5
Value	0	0

Population analysed: Safety Population For the Neurological Assessment at 12 months, only 21 subjects from the rhGDF-5 group completed the assessment (out of 22 total subjects) and 5 subjects from the Control group completed the assessment (out of 9 subjects total).

Primary outcome: 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. Number. Unit: participants

Measure	Intradiscal rhGDF-5 1.0mg n = 22	Vehicle Control n = 9
Value	0	0

Population analysed: Safety Population

Primary outcome: 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. Number. Unit: participants

Measure	Intradiscal rhGDF-5 n = 22	Vehicle Control n = 9
Value	0	1

Population analysed: Safety Population

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected through a 12 month period and annual telephone contact at 24 months and 36 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Intradiscal rhGDF-5	5 of 22 (22.7%)	16 of 22 (72.7%)	Not reported
Vehicle Control	2 of 9 (22.2%)	5 of 9 (55.6%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33945627Adoungotchodo 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

7 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Intradiscal rhGDF-5 in people with Early Lumbar Disc Degeneration, run by DePuy Spine at 7 sites in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Neurological Assessment for Motor Function and Reflexes/Sensory (time frame: 12 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01182337, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2016.