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

NCT04727385 | Unknown DMC

• 1 other identifier: 2019-A02476-51
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (10)

• The number of patients with at least one adverse event (AE) or serious adverse event (SAE)

  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)

  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

  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

  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

  Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L)

Study Arms (1)

single-arm of 3 cohorts

EXPERIMENTAL

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

Interventions

Double Crosslink Microgel DEVICE

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.

Also known as: DXM gel

single-arm of 3 cohorts

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female patient aged between 18 and 55 (inclusive)
• 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
• Oswestry Disability Index (ODI) ≥ 30% and ≤ 60%,
• Painful disc(s) between L1 and S1 represented
• For cohort 1L: at a single disc level
• For cohort 2L: at 2 disc levels
• For cohort 1-2L: at 1 or 2 disc levels
• Partial dehydration (grey disc) confirmed by MRI, grade II/III Pfirrmann classification
• Note:
• 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
• 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,
• Patient giving informed consent to take part in the study

You may not qualify if:

• Averted nerve root pain and potential root compression Note: Referred leg pain authorised
• Presence of posterior bone spurs (osteophytes)
• Partial or total Modic signal grade 1 at the considered disc level
• Patients with active systemic infection or infection localized to the site of the proposed implantation.
• Any conditions not described in the indications for use.
• Any mental conditions or neuromuscular disease that may generate an unacceptable risk of failure or postoperative complication.
• Patients with existing disc herniation at the considered level and on adjacent discs
• Endplate disease, defect or weakness, e.g. Schmorl nodule
• Vertebral bone abnormalities with active angioma
• Disc collapse ≥ 15% when disc height is compared to the height of the upper adjacent disc
• One lumbar disc rated grade IV or V on the Pfirrmann classification
• Imaging showing facet arthrosis
• Lytic spondylolisthesis
• Degenerative spondylolisthesis grade \> grade I Meyerding
• Congenital or idiopathic deformities of the spine (e.g. Scoliosis \>20° Cobb or Kyphosis)

Sponsors & Collaborators

• Gelmetix: lead
• Excelya: collaborator

Study Sites (1)

Polyclinique Bordeaux Nord Aquitaine Centre Vertebra

Bordeaux, 33300, France

RECRUITING

MeSH Terms

Conditions

Intervertebral Disc Degeneration; Intervertebral disc disease

Condition Hierarchy (Ancestors)

Spinal Diseases; Bone Diseases; Musculoskeletal Diseases

Central Study Contacts

David Goldsmith, Pr

CONTACT

+44 (0)1625 238 603; contact@gelmetix.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 13, 2021
• First Posted: January 27, 2021
• Study Start: September 15, 2020
• Primary Completion: October 1, 2021
• Study Completion: October 1, 2021
• Last Updated: January 27, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)