Clinical trial NCT04727385: Intervertebral DXM Gel Injection in Adults With Painful Lumbar Degenerative Disc Disease
Official title: First-in-human Pilot Study for the Safety Assessment of DXM Gel in Patients With Painful Lumbar Degenerative Disc Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Degenerative Disc Disease
Chronic Lower Back Pain
Discogenic Pain
Intervertebral Disc Degeneration
Lumbar Disc Disease
Lumbar Disc Degeneration
Lumbar Disc Pain
Keywords: Degenerative Disc Disease
Chronic Lower Back Pain
Double Cross-Linked hydrogel
disc nucleus
medical device
Double Crosslink Microgel
first in human
intervertebral disc space
Oswestry Disability Index
discs partial dehydration
proteoglycan matrix
Pfirrmann classification
inter-vertebral disc water content
Lead sponsor: Gelmetix
Sponsor class: INDUSTRY
Collaborators: name: Excelya
First posted: 2021-01-27
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an adaptative-design, interventional, open-label, single-arm trial performed at a single centre in France.

3 cohorts will be sequentially initiated according to the DSMB review of the safety parameters :

The safety primary endpoints of each cohort will be assessed by an independent Data Safety Monitoring Board (DSMB) at Day 42 post-injection to provide safety oversight on the patients and guidance on initiating the study on the next cohort.

Patients will be injected at day 0 and will be followed-up for a variable period according to the cohort.

* As the first enrolled cohort, the 1L cohort will have the longest follow-up (48 weeks) and will attend 9 visits.
* The second cohort (2L) will have a shorter follow-up period (36 weeks) attend the same visits except for V9, which will not be done.
* The third cohort (1-2L) will will have the shorter follow-up period (24 weeks) and will attend visits 1 to 7 except for V4, which will not be done.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: The number of patients with at least one adverse event (AE) or serious adverse event (SAE)
timeFrame: Between screening visit and 24 weeks (measured at each visits)
measure: The number of adverse events (AEs) or serious adverse event (SAEs)
timeFrame: Between screening visit and 24 weeks (measured at each visits)
measure: 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
timeFrame: Between screening visit and 24 weeks (measured at each visits)
measure: The change of the water content of the nucleus measured in milliseconds on the MRI during the follow-up period
timeFrame: Between screening visit and 24 weeks (measured at each visits)
measure: The modifications observed after the injection in the adjacent tissues of the injected nucleus
timeFrame: Between screening visit and 24 weeks (measured at each visits)
measure: The change of the intervertebral height in millimetres of the injected disc
timeFrame: Between screening visit and 24 weeks (measured at each visits)
measure: The change of the DXM gel position in relation to posterior and anterior limit of the annulus fibrosus and vertebral disc end-plates
timeFrame: Between screening visit and 24 weeks (measured at each visits)
Secondary outcomes:
measure: The number of patients with at least one adverse event (AE) or serious adverse event (SAE)
timeFrame: Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L)
measure: The number of adverse events (AEs) or serious adverse event (SAEs)
timeFrame: Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L)
measure: 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
timeFrame: Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L)
measure: The change of the water content of the nucleus measured in milliseconds on the MRI during the follow-up period
timeFrame: Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L)
measure: The modifications observed after the injection in the adjacent tissues of the injected nucleus
timeFrame: Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L)
measure: The change of the intervertebral height in millimetres of the injected disc
timeFrame: Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L)
measure: The change of the DXM gel position in relation to posterior and anterior limit of the annulus fibrosus and vertebral disc end-plates
timeFrame: Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L)
measure: Oswestry disability index (ODI)
timeFrame: Measured and compared to baseline at the different time points of the flowchart according to the cohort (over 24 to 48 weeks)
measure: Visual analogue scale (VAS) self-assessment
timeFrame: Measured and compared to baseline at the different time points of the flowchart according to the cohort (over 24 to 48 weeks)
measure: Working status
timeFrame: measured and compared to baseline at the different time points of the flowchart according to the cohort (over 24 to 48 weeks)
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine Centre Vertebra
Study officials:
References: