Intervertebral DXM Gel Injection in Adults With Painful Lumbar Degenerative Disc Disease (DXM gel)

First-in-human Pilot Study for the Safety Assessment of DXM Gel in Patients With Painful Lumbar Degenerative Disc Disease

The purpose of this study is to assess the safety and the efficacy of an hydrogel (double cross-link microgel - DXM) injection into the intervertebral disc (IVD) space in patients with painful lumbar degenerative disc disease (DDD) over 24 to 48 weeks.

Study Overview

• Status: Recruiting
• Conditions: Degenerative Disc Disease; Intervertebral Disc Degeneration; Discogenic Pain; Lumbar Disc Degeneration; Lumbar Disc Disease; Chronic Lower Back Pain; Lumbar Disc Pain
• Intervention / Treatment: Device: Double Crosslink Microgel

Detailed Description

After being informed of the study and the potential risks, all patients matching the eligibility criteria and who have given their written consent will undergo a gel injection at day 0 after a period of screening of up to 14 days.

Then, they will be followed-up for a variable period according to the cohort :

• first cohort of 5 patients with only one disc to be treated will be followed during 48 weeks,
• second cohort of 5 patients with 2 discs to be treated will be followed during 36 weeks,
• third cohort of 10 patients with 1 or 2 discs to be treated will be followed during 24 weeks.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: David Goldsmith, Pr; Phone Number: +44 (0)1625 238 603; Email: contact@gelmetix.com

Study Locations

• France
  • Bordeaux, France, 33300
    • Recruiting
    • Polyclinique Bordeaux Nord Aquitaine Centre Vertebra
    • Contact: Jean-Charles LE HUEC, Pr; Phone Number: +33 5 64 60 15 47; Email: vertebra@bordeauxnord.com
    • Contact: Stéphane BOURRET; Phone Number: +33 5 56 43 71 11; Email: s.bourret@bordeauxnord.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female patient aged between 18 and 55 (inclusive)
2. Discogenic low back pain, confirmed by a history of Low Back Pain, with a minimum of 3 months of continuous pain or 6 months of acute episodes of pain despite the conservative treatment including painkillers and physiotherapy
3. Oswestry Disability Index (ODI) ≥ 30% and ≤ 60%,

4. Painful disc(s) between L1 and S1 represented

   1. For cohort 1L: at a single disc level
   2. For cohort 2L: at 2 disc levels
   3. For cohort 1-2L: at 1 or 2 disc levels
5. Patients with a Zung depression score ≤ 49, Note: Patients with a Zung depression score between ≥ 50 and ≤ 64 may be included if deemed suitable for trial inclusion by the investigator

6. Partial dehydration (grey disc) confirmed by MRI, grade II/III Pfirrmann classification

   Note:

   • Pfirrmann Grade I lesions are not contra-indications to recruitment, but can never be the target of any intervention in this trial. Patients featuring grade I disc(s) in conjunction with a grade II/III meet the inclusion criteria for his(her) disc Grade II/III disc to be treated
   • Pfirrmann Grade IV and V disc lesions are absolute contra-indications for inclusion
7. Female patients of childbearing potential must have a negative urine pregnancy test at screening and use an effective birth control during the follow up period after the injection procedure
8. Patients who are willing and capable of understanding the investigator's explanations, following his instructions and adhering to the follow-up visits according to the study protocol, including a willingness and ability to undergo MRI scanning,
9. Patient giving informed consent to take part in the study

Exclusion Criteria:

1. Averted nerve root pain and potential root compression Note: Referred leg pain authorised
2. Presence of posterior bone spurs (osteophytes)
3. Partial or total Modic signal grade 1 at the considered disc level
4. Patients with active systemic infection or infection localized to the site of the proposed implantation.
5. Any conditions not described in the indications for use.
6. Any mental conditions or neuromuscular disease that may generate an unacceptable risk of failure or postoperative complication.
7. Patients with existing disc herniation at the considered level and on adjacent discs
8. Endplate disease, defect or weakness, e.g. Schmorl nodule
9. Vertebral bone abnormalities with active angioma
10. Disc collapse ≥ 15% when disc height is compared to the height of the upper adjacent disc
11. One lumbar disc rated grade IV or V on the Pfirrmann classification
12. Imaging showing facet arthrosis
13. Lytic spondylolisthesis
14. Degenerative spondylolisthesis grade > grade I Meyerding
15. Congenital or idiopathic deformities of the spine (e.g. Scoliosis >20° Cobb or Kyphosis)
16. Old or acute vertebral fractures in the lumbar spine
17. Patients with any prior spine procedure in the lumbar spine
18. Any skin disease or inadequate tissue coverage at the site of the injection

19. Any medical or surgical conditions that could preclude the potential benefit of disc injection must be carefully analysed before the procedure, such as congenital abnormalities, immunosuppressive disease, elevation of erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) concentration not explained by other diseases, elevation of white blood cell (WBC) count, or marked left shift in the WBC differential count, should be carefully taken into consideration prior to the surgical procedure.

    Note: These contra-indications can be relative or absolute and must be taken into account by the physician when making his decision. The above list is not exhaustive.

20. Tumours with any metastatic potential, or known metastases, in any part of the body
21. Known infection with HIV or Hepatitis B, C or E
22. Patient that has received or is seeking employee compensation
23. Zung depression score ≥ 65
24. Substance abuse or dependency (pharmaceuticals, drugs, alcohol)
25. Disabling obesity (BMI > 35kg/m²)
26. History of chemical dependency (e.g. illicit drugs, or opiates) or significant emotional or psychosocial disturbance which may have an effect on treatment outcome
27. Patients who are pregnant, breast feeding or planning pregnancy during the study
28. Anticoagulation (beyond low level prophylactic doses of single anti-platelet agents)
29. Inability to undertake or known contra-indications to MRI scanning
30. Known hypersensitivity to barium sulphate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: single-arm of 3 cohorts; These patients will be sequentially recruited in 3 cohorts : One disc level cohort: 5 patients with only one disc to be treated; First enrolled cohort with 48 weeks of follow-up (9 visits V1-V9); Two disc level cohort: 5 patients with 2 discs to be treated; Second enrolled cohort with 36 weeks of follow-up (8 visits, same visits except for V9); One or two disc level cohort: 10 patients with 1 or 2 discs to be treated; Third enrolled cohort with 24 weeks of follow-up (6 visits, V1 to 7 except for V4)

Device: Double Crosslink Microgel; DXM hydrogel is a pH responsive Double Cross-Linked microgel based on single internally cross-linked microspheres (comprising a methacrylic acid-methyl methacrylate-ethylene glycol dimethacrylate copolymer) The DXM gel is injected into the intervertebral disc (IVD) space via a standardised procedure similar to the routinely-performed Discography procedure. The disc approach described in the discography procedure has been reported to allow the injection of a solution in the centre of the disc. The injection of the gel takes about 2 min.; Other Names: DXM gel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of patients with at least one adverse event (AE) or serious adverse event (SAE)	An adverse event (AE) is any untoward medical occurrence in a patient exposed to a medical device and which does not necessarily have a causal relationship with this medical device. An AE can therefore be any unintended disease or injury or clinical signs (including an abnormal laboratory finding) in subjects, users or other persons whether or not considered related to the investigational medical device. A serious adverse event (SAE) is defined as an AE that: led to a death, injury or permanent impairment to a body structure or a body function;; led to a serious deterioration in health of the subject, that either resulted in: a life-threatening illness or injury, or a permanent impairment of a body structure or a body function, or in-patient hospitalization or prolongation of existing hospitalization, or in medical or surgical intervention to prevent life threatening illness; led to foetal distress, foetal death or a congenital abnormality or birth defect.	Between screening visit and 24 weeks (measured at each visits)
The number of adverse events (AEs) or serious adverse event (SAEs)	An adverse event (AE) is any untoward medical occurrence in a patient exposed to a medical device and which does not necessarily have a causal relationship with this medical device. An AE can therefore be any unintended disease or injury or clinical signs (including an abnormal laboratory finding) in subjects, users or other persons whether or not considered related to the investigational medical device. A serious adverse event (SAE) is defined as an AE that: led to a death, injury or permanent impairment to a body structure or a body function;; led to a serious deterioration in health of the subject, that either resulted in: a life-threatening illness or injury, or a permanent impairment of a body structure or a body function, or in-patient hospitalization or prolongation of existing hospitalization, or in medical or surgical intervention to prevent life threatening illness; led to foetal distress, foetal death or a congenital abnormality or birth defect.	Between screening visit and 24 weeks (measured at each visits)
The number of patients with neurological changes during the follow-up period according to the evaluation of nerve root pain, sensory deficit and motor deficit	The neurological evaluation will look more specifically for: The presence or absence of nerve root pain and its localisation (i.e. Lassegue test); The presence of deferred pain in the leg without deficit; The presence or absence of sensory deficit and its localisation; The presence or absence of motor deficit and its classification from grade 1 to 5 (0 - Total Paralysis, 1 - Palpable or Visible, 2 - Active Movement, gravity eliminated, 3 - Active Movement, against gravity, Contraction, 4 - Active Movement, against some resistance, 5 - Active Movement, against full resistance (normal muscular force))	Between screening visit and 24 weeks (measured at each visits)
The change of the water content of the nucleus measured in milliseconds on the MRI during the follow-up period	The Magnetic resonance imaging (MRI) will allow the observation.	Between screening visit and 24 weeks (measured at each visits)
The modifications observed after the injection in the adjacent tissues of the injected nucleus	The Magnetic resonance imaging (MRI) will allow the observation of the corresponding adjacent tissues: Annulus fibrosus; Endplates; Facets	Between screening visit and 24 weeks (measured at each visits)
The change of the intervertebral height in millimetres of the injected disc	The Magnetic resonance imaging (MRI) will allow the observation.	Between screening visit and 24 weeks (measured at each visits)
The change of the DXM gel position in relation to posterior and anterior limit of the annulus fibrosus and vertebral disc end-plates	The Magnetic resonance imaging (MRI) will allow the observation.	Between screening visit and 24 weeks (measured at each visits)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of patients with at least one adverse event (AE) or serious adverse event (SAE)	An adverse event (AE) is any untoward medical occurrence in a patient exposed to a medical device and which does not necessarily have a causal relationship with this medical device. An AE can therefore be any unintended disease or injury or clinical signs (including an abnormal laboratory finding) in subjects, users or other persons whether or not considered related to the investigational medical device. A serious adverse event (SAE) is defined as an AE that: led to a death, injury or permanent impairment to a body structure or a body function;; led to a serious deterioration in health of the subject, that either resulted in: a life-threatening illness or injury, or a permanent impairment of a body structure or a body function, or in-patient hospitalization or prolongation of existing hospitalization, or in medical or surgical intervention to prevent life threatening illness; led to foetal distress, foetal death or a congenital abnormality or birth defect.	Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L)
The number of adverse events (AEs) or serious adverse event (SAEs)	An adverse event (AE) is any untoward medical occurrence in a patient exposed to a medical device and which does not necessarily have a causal relationship with this medical device. An AE can therefore be any unintended disease or injury or clinical signs (including an abnormal laboratory finding) in subjects, users or other persons whether or not considered related to the investigational medical device. A serious adverse event (SAE) is defined as an AE that: led to a death, injury or permanent impairment to a body structure or a body function;; led to a serious deterioration in health of the subject, that either resulted in: a life-threatening illness or injury, or a permanent impairment of a body structure or a body function, or in-patient hospitalization or prolongation of existing hospitalization, or in medical or surgical intervention to prevent life threatening illness; led to foetal distress, foetal death or a congenital abnormality or birth defect.	Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L)
The number of patients with neurological changes during the follow-up period according to the evaluation of nerve root pain, sensory deficit and motor deficit	The neurological evaluation will look more specifically for: The presence or absence of nerve root pain and its localisation (i.e. Lassegue test); The presence of deferred pain in the leg without deficit; The presence or absence of sensory deficit and its localisation; The presence or absence of motor deficit and its classification from grade 1 to 5 (0 - Total Paralysis, 1 - Palpable or Visible, 2 - Active Movement, gravity eliminated, 3 - Active Movement, against gravity, Contraction, 4 - Active Movement, against some resistance, 5 - Active Movement, against full resistance (normal muscular force))	Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L)
The change of the water content of the nucleus measured in milliseconds on the MRI during the follow-up period	The Magnetic resonance imaging (MRI) will allow the observation.	Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L)
The modifications observed after the injection in the adjacent tissues of the injected nucleus	The Magnetic resonance imaging (MRI) will allow the observation of the corresponding adjacent tissues: Annulus fibrosus; Endplates; Facets	Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L)
The change of the intervertebral height in millimetres of the injected disc	The Magnetic resonance imaging (MRI) will allow the observation.	Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L)
The change of the DXM gel position in relation to posterior and anterior limit of the annulus fibrosus and vertebral disc end-plates	The Magnetic resonance imaging (MRI) will allow the observation.	Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L)
Oswestry disability index (ODI)	The ODI score is based on a self-completed questionnaire of 10 items to measure a patient's permanent functional disability. It is a well-recognised, gold standard orthopaedic score devised in 1980 and which still remains the best and most reliable measure of the overall impact of spinal disease associated with low back pain and any interventions patients may receive. It has been repeatedly used for natural history studies, cohort studies, and for many device and surgery interventions. It is reproducible, reliable and responsive to therapeutic interventions.	Measured and compared to baseline at the different time points of the flowchart according to the cohort (over 24 to 48 weeks)
Visual analogue scale (VAS) self-assessment	The visual analogue self-assessment scale is an evaluation performed by the patient to specify his level of pain on a scale of 'no pain' to 'extreme pain'. During the site visit, the VAS is to be filled on-site by the patient and collected by the site staff.	Measured and compared to baseline at the different time points of the flowchart according to the cohort (over 24 to 48 weeks)
Working status	The working status will be collected by interviewing the patient about his/her work activity.	measured and compared to baseline at the different time points of the flowchart according to the cohort (over 24 to 48 weeks)

Collaborators and Investigators

• Sponsor: Gelmetix
• Collaborators: Excelya

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2020
• Primary Completion (Anticipated): October 1, 2021
• Study Completion (Anticipated): October 1, 2021

Study Registration Dates

• First Submitted: January 13, 2021
• First Submitted That Met QC Criteria: January 22, 2021
• First Posted (Actual): January 27, 2021

Study Record Updates

• Last Update Posted (Actual): January 27, 2021
• Last Update Submitted That Met QC Criteria: January 22, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: medical device; Degenerative Disc Disease; Oswestry Disability Index; first in human; Chronic Lower Back Pain; Double Cross-Linked hydrogel; disc nucleus; Double Crosslink Microgel; intervertebral disc space; discs partial dehydration; proteoglycan matrix; Pfirrmann classification; inter-vertebral disc water content
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Bone Diseases; Back Pain; Low Back Pain; Intervertebral Disc Degeneration; Spinal Diseases
• Other Study ID Numbers: 2019-A02476-51

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No