Trial Outcomes & Findings for 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 (NCT NCT01124006)

Last Updated: 2016-02-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

12 months

Results posted on

2016-02-24

Participant Flow

Participant milestones

Participant milestones
Measure	Intradiscal rhGDF-5 (1.0mg) 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.	Placebo Excipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection	Intradiscal rhGDF-5 (2.0mg) 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.
Overall Study STARTED	10	10	4
Overall Study COMPLETED	7	8	2
Overall Study NOT COMPLETED	3	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Intradiscal rhGDF-5 (1.0mg) 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.	Placebo Excipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection	Intradiscal rhGDF-5 (2.0mg) 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.
Overall Study Withdrawal by Subject	2	2	0
Overall Study Lost to Follow-up	1	0	1
Overall Study Other	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Intradiscal rhGDF-5 (1.0mg) n=10 Participants 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.	Placebo n=10 Participants Excipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection	Intradiscal rhGDF-5 (2.0mg) n=4 Participants 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.	Total n=24 Participants Total of all reporting groups
Age, Continuous	39.7 years STANDARD_DEVIATION 9.56 • n=5 Participants	44.7 years STANDARD_DEVIATION 7.86 • n=7 Participants	42.4 years STANDARD_DEVIATION 6.38 • n=5 Participants	42.2 years STANDARD_DEVIATION 8.40 • n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	7 Participants n=7 Participants	3 Participants n=5 Participants	16 Participants n=4 Participants
Region of Enrollment United States	10 participants n=5 Participants	10 participants n=7 Participants	4 participants n=5 Participants	24 participants n=4 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Safety Population For the Neurological Assessment at 12 months, only 8 subjects from the rhGDF-5 1.0mg group (out of 10 subjects total) completed the assessment, only 3 subjects from the rhGDF-5 2.0mg group (out of 4 subjects total) completed the assessment, and none of the placebo subjects (out of 10 total subjects) completed the assessment.

Outcome measures

Outcome measures
Measure	Intradiscal rhGDF-5 (1.0mg) n=8 Participants 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.	Placebo Excipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection	Intradiscal rhGDF-5 (2.0mg) n=3 Participants 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.
Neurological Assessment for Motor Function and Reflexes/Sensory	0 participants	—	0 participants

PRIMARY outcome

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

Population: Safety Population

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

Outcome measures

Outcome measures
Measure	Intradiscal rhGDF-5 (1.0mg) n=10 Participants 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.	Placebo n=10 Participants Excipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection	Intradiscal rhGDF-5 (2.0mg) n=4 Participants 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.
Treatment Emergent Adverse Events- Relationship to Study Drug	0 participants	0 participants	0 participants

PRIMARY outcome

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

Population: Safety Population

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

Outcome measures

Outcome measures
Measure	Intradiscal rhGDF-5 (1.0mg) n=10 Participants 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.	Placebo n=10 Participants Excipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection	Intradiscal rhGDF-5 (2.0mg) n=4 Participants 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.
Treatment Emergent Adverse Events- Relationship to Study Drug	4 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: 12-month

Population: FAS Population

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.

Outcome measures

Outcome measures
Measure	Intradiscal rhGDF-5 (1.0mg) n=10 Participants 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.	Placebo n=10 Participants Excipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection	Intradiscal rhGDF-5 (2.0mg) n=4 Participants 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.
Change in Function Assessed by Oswestry Disability Index Change at 12 Months From Baseline.	-19.8 units on a scale Standard Deviation 21.22	-18.8 units on a scale Standard Deviation 22.43	-6.0 units on a scale Standard Deviation 29.98

SECONDARY outcome

Timeframe: 12 months

Population: FAS Population

The Visual Analogue Scale (VAS) pain score asks the subject to place a vertical mark on a horizontal line ( that is approximately 10cm long) with 'No Pain' (score of 0=0cm) 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.

Outcome measures

Outcome measures
Measure	Intradiscal rhGDF-5 (1.0mg) n=10 Participants 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.	Placebo n=10 Participants Excipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection	Intradiscal rhGDF-5 (2.0mg) n=4 Participants 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.
Change in Pain Visual Analogue Scale (VAS) at 12 Months From Baseline.	-2.33 units on a scale Standard Deviation 3.645	-2.78 units on a scale Standard Deviation 3.751	-1.10 units on a scale Standard Deviation 3.336

SECONDARY outcome

Timeframe: 12 months

Population: FAS Population One subject from the rhGDF-5 1.0mg group (out of 10 subjects total) did not complete the PCS, SF-36 at 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)

Outcome measures

Outcome measures
Measure	Intradiscal rhGDF-5 (1.0mg) n=9 Participants 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.	Placebo n=10 Participants Excipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection	Intradiscal rhGDF-5 (2.0mg) n=4 Participants 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.
Change in Physical Component Summary of Quality of Life Measure Assessed by Short-Form 36 at 12 Months From Baseline.	7.22 units on a scale Standard Deviation 9.728	8.61 units on a scale Standard Deviation 14.213	6.21 units on a scale Standard Deviation 8.245

SECONDARY outcome

Timeframe: 12 months

Population: FAS Population One subject from the rhGDF-5 1.0mg group (out of 10 subjects total) did not complete the MCS, SF-36 at Baseline.

Outcome measures

Outcome measures
Measure	Intradiscal rhGDF-5 (1.0mg) n=9 Participants 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.	Placebo n=10 Participants Excipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection	Intradiscal rhGDF-5 (2.0mg) n=4 Participants 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.
Change in Mental Component Summary Quality of Life Measure Assessed by Short Form SF-36 at 12 Months From Baseline.	2.86 units on a scale Standard Deviation 11.142	-0.92 units on a scale Standard Deviation 9.163	1.31 units on a scale Standard Deviation 20.276

Adverse Events

Intradiscal rhGDF-5 (1.0mg)

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Intradiscal rhGDF-5 (2.0mg)

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Intradiscal rhGDF-5 (1.0mg) n=10 participants at risk 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.	Placebo n=10 participants at risk Excipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection	Intradiscal rhGDF-5 (2.0mg) n=4 participants at risk 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.
Musculoskeletal and connective tissue disorders Intervertebral Disc Protrusion	0.00% 0/10 • Adverse events were collected through a 12 month period and annual telephone contact at 24 months and 36 months.	0.00% 0/10 • Adverse events were collected through a 12 month period and annual telephone contact at 24 months and 36 months.	25.0% 1/4 • Number of events 1 • Adverse events were collected through a 12 month period and annual telephone contact at 24 months and 36 months.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/10 • Adverse events were collected through a 12 month period and annual telephone contact at 24 months and 36 months.	0.00% 0/10 • Adverse events were collected through a 12 month period and annual telephone contact at 24 months and 36 months.	25.0% 1/4 • Number of events 1 • Adverse events were collected through a 12 month period and annual telephone contact at 24 months and 36 months.

Other adverse events

Additional Information

Mark Lotito

DePuy Synthes Spine

Phone: 508-880-8045

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Clinical Investigators may freely present or publish results of the Clinical Investigation in a manner which fairly sets forth the conclusions reached by the Clinical Investigators, but only after the Sponsor has been given the opportunity of reviewing the proposed presentation or publication at least 60 days prior to the intended submission, presentation, or publication date.
Publication restrictions are in place

Restriction type: OTHER