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Intervertebral Disc DisplacementPhase 1/2NDiscNCT01640457

Safety and Efficacy With NOVOCART® Disc Plus (ADCT) for the Treatment of Degenerative Disc Disease in Lumbar Spine

A Phase 1/2 study testing NOVOCART® Disc plus and NOVOCART® Disc basic in people with Intervertebral Disc Displacement and Intervertebral Disc Degeneration, run by Tetec AG at 10 sites in 2 countries.

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

NOVOCART® Disc plus is being investigated to explore its clinical applicability, safety and efficacy in the repair of a herniated disc with an indication for an elective sequestrectomy, and of the adjacent degenerated disc, if present. Read more about this study

Who is it for?
Ages 18 to 60 years
What is being tested?
NOVOCART® Disc plus and NOVOCART® Disc basic
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
120 participants
Where
10 sitesin 2 countries
Study dates
Aug 2012to 14 Jun 2021
Phase
Phase 1/2
Are there results?
None posted in the registry

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 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • The patient has a disc herniation with back and/or leg pain (radicular pain)
  • The patient has an indication for sequestrectomy according to the guidelines of DGNC and DGOOC
  • The patient is between 18-60 years of age.
  • The patient is physically and mentally able to participate in the study, and is able to understand the study, its goals and the possible risk factors involved. The patient is willing and able to participate in the follow-up visit plan at the study site and is able to understand and to complete study-relevant questionnaires in German language.
  • The patient is sufficiently informed about this trial orally and in writing. S/he had enough time for consideration, is willing to participate in the study and gives her/his written in-formed consent.
  • The patient confirms that s/he did not participate in a clinical study 90 days prior study inclusion. S/he agrees to refrain from participating in another clinical study during the NOVOCART® Disc Study and for another 90 days after study termination
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  • Radiological Inclusion Criteria
  • Patients must meet all of the following criteria to be considered for enrollment in the NOVO-CART® Disc study.
  • The patient has a single-level lumbar disc herniation
  • The patient has more than 50% remaining disc height in the herniated disc in comparison to unaffected discs in the lumbar spine. If all discs show degenerative signs, disc height has to be at least 5 mm
  • The patient has no obvious signs of osteophytes and no end plate sclerosis in the lumbar segment to be treated with NOVOCART® Disc plus oder NOVOCART® Disc basic
  • Patients without adjacent degenerative disc (HD):
  • 4. The adjacent proximal disc has no degenerative signs according to Pfirrmann Score stage 3 to 5.
  • Patients with adjacent degenerative disc (AAD):
  • 4. The patients has additional degenerative signs in the proximal adjacent lumbar level ac-cording to Pfirrmann 3-4, but no more than 25% disc height reduction

Who cannot join

  • The patient has had a previous surgery at the lumbar level(s) and has been treated with NOVOCART® Disc plus oder NOVOCART® Disc basic.
  • The patient had a past recurrent disc herniation treated with sequestrectomy of the relevant disc.
  • The patient has any degenerative muscular or neurological condition that would interfere with evaluation of outcome measures including but not limited to Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, muscular dystrophy and myelopathic diseases of different causes.
  • BMI > 35 kg/m2
  • The patient has current or recent history of illicit drug, nicotine (more than 20 cigarettes per day) or alcohol abuse or dependence
  • CRP > 10mg/dl
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  • The patient is pregnant, breastfeeding or actual planning to become pregnant. Female patients must be either at least two years postmenopausal or using one of the following means of birth control during the treatment phase, i.e. to transplantation
  • surgical sterility
  • double barrier methods, e.g. condom or diaphragm in combination with spermicide
  • intrauterine contraceptive device
  • bilateral vasectomy of sexual partner at least 90 days prior to enrolment in combination with barrier methods (e.g. condom or diaphragm)
  • birth control pill
  • The patient has a history of known allergies or a suspicion of allergies to any of the NO-VOCART® Disc plus oder basic product components including hyaluronan, polyethylenglycol or albumin
  • Immune defects or the affinity for infections of known or unknown causes
  • The patient has a active systemic or local microbial infection, eczematization or inflammable skin alterations at the site of surgery (including Protozoonosis: Babesiosis, Trypanosomiasis (e.g. Chagas-Disease), Leishmaniasis, persistent bacterial infections, like Brucellosis, spotted and typhus fever, other Rickettsiosis, Leprosy, Recurrent Fever, Melioidosis or Tularaemia).
  • The patient is unable to undergo magnetic resonance imaging (MRI)
  • The patient has a history or a suspicion of a disease with chronically inflammable character, as rheumatoid arthritis, gout, pseudo-gout, metabolic bone diseases, Crohn's disease, ulcerative colitis, lupus erythematosus, or other autoimmune disorders
  • Known osteoporosis
  • The patient has a primary hyperparathyroidism or hyperthyroidism, has chronic renal failure or has had previous fragility fractures.
  • Systemic connective tissue or collagen disease
  • Hereditary ocular degenerations with unclear diagnosis, retinopathies based on connective tissue-defined causes, macular corneal dystrophy, (based on the fact that the human cornea expresses cartilage specific proteins as essential functional elements and thus may serve as an indicator for paralleling degenerative events in various cartilaginous tissues)
  • The patient has immune suppression
  • The patient has a history of blood coagulation disease of different genesis, including known haemorrhagic diathesis of unknown cause
  • The patient had undergone chemo or radiotherapy within the past 5 years, or had any cancer other than non-melanoma skin cancer treated with curative intent within the past 5 years
  • Known diabetes, drug treated
  • Ulterior concomitant diseases or functional impairments of specific organs, which exclude study participation by the assessment of the investigator
  • The patient is a prisoner
  • Radiological Exclusion Criteria
  • 1. The patient has apparent degenerative changes in the lumbar spine as determined by Modic Changes 2-3 2. The patient has one or more dysplastic vertebral bodies within the lumbar spine 3. The patient has a sacralised lumbar vertebra LWK5 at the level to be treated with NOVOCART® Disc plus oder NOVOCART® Disc basic 4. The patient has previous or acute spondylodiscitis 5. Segmental instability (spondylolisthesis > 5 mm) or translation > 3 mm 6. The patient has a isthmic spondylolisthesis, ankylosing spondylitis or spondylolysis 7. The patient has lumbar scoliosis (> 11° deformation). 8. The patient has previous trauma, discography or any other surgical intervention at the lumbar spine .
  • 9. The patient has previous compression or burst fracture at the level(s) to be treated with NOVOCART® Disc plus or NOVOCART® Disc basic 10. The patient has a central spinal canal stenosis with evidence of a narrowing of < 8 mm (by MRI, sagittal ) 11. The patient has a spinal tumor 12. The patient has metabolic bone disease 13. The patient has facet ankylosis or severe facet degeneration. 14. The patient has a lumbar kyphosis
  • Intra-surgery (tissue explant/sequestrectomy) Exclusion Criteria
  • 1. Extensive damage of the Anulus, which subsequently poses a significantly greater risk of recurrence.
  • Exclusion criteria determined after tissue explant/sequestrectomy
  • HIV infection
  • Treponema pallidum (syphilis) infection
  • active hepatitis B or C infection
  • 1. Recurrent disc herniation after surgery and prior transplantation/implantation.

Trial locations and contacts

10 sites in 2 countries.

10 sites in 2 countries

Germany9 sites

  • Charité Universitätsmedizin

    Berlin, 13353

  • DRK Kliniken Berlin Westend

    Berlin, 14050

  • University Hospital Duesseldorf

    Düsseldorf, 40225

  • Universitätsmedizin

    Göttingen, 37075

  • Hospital "BG-Kliniken Bergmannstrost"

    Halle, 06112

  • SHG Klinikum

    Idar-Oberstein, 55743

  • Städtisches Klinikum

    Karlsruhe, 76133

  • St. Franziskus Hospital

    Münster, 48145

  • Berufsgenossenschaftliche Unfallklinik

    Murnau am Staffelsee, 82418

Other trials in Germany

Austria1 site

  • University Hospital for Neurosurgery Innsbruck

    Innsbruck, Tyrol, 6020

Other trials in Austria

About this study

Official title: A Prospective Randomized Multicentre Phase I/II Clinical Trial to Evaluate Safety and Efficacy of NOVOCART® Disc Plus Autologous Disc Chondrocyte Transplantation (ADCT) in the Treatment of Nucleotomized and Degenerative Lumbar Discs to Avoid Secondary Disease

NOVOCART® Disc plus is being investigated to explore its clinical applicability, safety and efficacy in the repair of a herniated disc with an indication for an elective sequestrectomy, and of the adjacent degenerated disc, if present. The objective of this clinical study is to provide basis for a confirmatory study design (endpoints, methodologies) (Phase II), and to develop a safety profile (Phase I). This study further aims at developing and validating known and new biologic markers for the quality and clinical efficacy of the product as requested in the context of identity, purity and potency characteristics of the medicinal/investigational product.

Read the detailed description

This is a classical Phase II study with an implicated Phase I part. The Phase I/II combination study is a non-confirmatory study aimed at gathering preliminary clinical information on NOVOCART® Disc plus used in a new indication in the repair of a herniated disc. It will be conducted in a prospective, multicenter, unmasked, clinical trial including 120 subjects randomized to NOVOCART® Disc plus (NDplus, 60 subjects), media NOVOCART® Disc basic with no active cell component (NDbasic, 36 subjects) and to standard of care (SC) sequestrectomy as control (24 subjects). 24 patients will be enrolled in Phase I of the study (12 NDplus, 12 NDbasic) and 96 patients in Phase II (48 NDplus, 24 NDbasic, 24 SC).

All subjects will be evaluated at 1.5-, 3-, 6-, 12-, 24-, 36-, 48-months post-t0 examination in the SC study arm and 1.5-, 3-, 6-, 12-, 24-, 36-, 48-months post-t5 examination in the NDplus and NDbasic study arms, and then 5 years post-t0/t5 to collect long-term clinical data. Efficacy measurements for functional improvement will be evaluated among NDplus, NDbasic and SC. Physiological effects observed from MRI measurements will be compared between appropriate treatments depending on expected treatment mechanisms. Safety data of NDplus will be combined with NDbasic to contrast against SC on procedure related risks and NDplus against NDbasic and SC together on graft-related adverse experiences.

To optimize the usefulness of clinical information, data collected in the study may be analyzed and reviewed continuously. Early findings may be used to modify the study design when deemed appropriate and acceptable by the Sponsor's medical advisors. Data-driven adaptive actions include but are not limited to stopping enrollment early. The Sponsor will inform regulatory bodies, Ethic Committees, and investigators before implementing study design modifications.

Cells and tissues collected from this study will be used in other in vitro-controlled experiments aimed at developing and validating known and novel biologic markers to quantify cell quality in the context of identity, purity and potency. Prognostic values of these biologic markers will be examined by correlating them with clinical data collected in this study.

The study will follow each subject for a total of five years post-t0 examination in the SC study arm and post-t5 examination in the NDplus and NDbasic study arms to obtain long-term performance data.

Patients must have a single-level acute disc herniation with an indication for an elective sequestrectomy. They may further have corresponding disc degeneration in the proximal adjacent segment (Pfirrmann Score Stage 3-4). A total of 120 adults will be enrolled in this study.

Each patient will remain in the study for 5 years post t0/t5 examination to complete the planned follow-up phase. It is expected to take 6 years and five months to collect all required data for this study.

Being tested
NOVOCART® Disc plus, NOVOCART® Disc basic
Keywords
degenerative disc, herniated disc, sequestrectomy, Autologous Disc Chondrocyte Transplantation, nucleotomy, safety, efficacy, treatment, lumbar spine, low back pain, adjacent degenerative disc, black disc, NOVOCART
Medical subject headings
Intervertebral Disc Displacement, Intervertebral Disc Degeneration, Low Back Pain

What participants receive

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

  • NOVOCART® Disc plusDrug

    Autologous Disc Chondrocyte Transplantation System (ADCT)

  • NOVOCART® Disc basicDevice

    ADCT (Media with no active cell component)

Study groups in NCT01640457
Study groupRoleWhat they receive
NDplusExperimentalNOVOCART® Disc plus (Autologous Disc Chondrocyte Transplantation System)
Receives: Drug: NOVOCART® Disc plus
NDbasicPlacebo comparatorNOVOCART® Disc basic (media with no active cell component)
Receives: Device: NOVOCART® Disc basic
Sequestrectomy only (SC)No interventionSequestrectomy (standard of care)

What is being measured

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

  1. Oswestry Disability Index (ODI)

    Primary efficacy variable.

    Early evaluation for efficacy will be performed when all patients completed scheduled 12-months follow-up visit (Interim analysis).

    Measured: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) to 12-months follow-up

  2. Oswestry Disability Index (ODI)

    Primary efficacy variable.

    Primary evaluation for efficacy will be performed when all patients completed scheduled at 24-months follow-up visit (Interim analysis).

    Measured: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) to 24-months follow-up

  3. Oswestry Disability Index (ODI)

    Primary efficacy variable.

    Final analysis will be performed when all patients completed scheduled 60-months follow-up visit.

    Measured: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) to 60-months follow-up

Secondary outcomes (17)

  1. MRI-signal (disc height, disc volumetry, signal intensity)

    Secondary efficacy variable

    Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

    Measured: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up

  2. Oswestry Disability Index

    Secondary efficacy variable

    Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

    Measured: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up

  3. VAS for back pain and leg pain

    Secondary efficacy variable

    Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

    Measured: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up

  4. Health-related quality of life as measured by the SF-36

    Secondary efficacy variable

    Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

    Measured: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up

  5. Healthy Questionnaire EQ-5D

    Secondary efficacy variable

    Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

    Measured: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up

  6. Neurological status

    Secondary efficacy variable

    Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

    Measured: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up

  7. Functional status

    Secondary efficacy variable

    Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

    Measured: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up

  8. Return to work (days)

    Secondary efficacy variable

    Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

    Measured: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up

  9. Analgesic Medication Use during the previous 14-day-time period

    Secondary efficacy variable

    Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

    Measured: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up

  10. Physician assessments of ease of transplantation

    Outcome to quantify feasibility of procedure

    When all NDplus and NDbasic patients completed transplantation procedure.

    Measured: transplantation

  11. Surgical parameters, including length of procedure

    Outcome to quantify feasibility of procedure

    When all enrolled patients completed sequestrectomy and if applicable transplantation procedure.

    Measured: Sequestrectomy and transplantation

  12. Prevalence of subsequent surgical interventions

    Outcome to Quantify Safety

    A subsequent surgical intervention is defined as any invasive procedure performed at the index level to treat the same condition (herniation) or other conditions resulted from the transplantation/implantation procedure within the 12-month period post-operation.

    Measured: 12-months post-operation

  13. Any unanticipated adverse event

    Outcome to Quantify Safety

    Measured: Baseline assessment 1<45d pre-sequestrectomy up to 60-months follow-up at any scheduled and unscheduled visit

  14. Specific laboratory parameters according to product compatibility and availability: CRP, IL-6, LTE4

    Outcome to Quantify Safety (Phase I only)

    At sequestrectomy, 2h-, 6h-, 24h-, 36h- post surgery, transplantation, direct after transplantation, 6h-, 12h-, 18h-, 24h-, 30h-, 36h-, 42h-, 48h- post transplantation, 3 and 6 weeks post transplantation

    Measured: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 1,5-months follow-up

  15. Histology of the tissue explant

    Outcome to Develop and Validate Biological Markers

    Measured: Sequestrectomy

  16. Gene expression by quantitative realtime PCR of expanded cells, and cell culture medium metabolites during expansion

    Outcome to Develop and Validate Biological Markers

    Measured: Transplantation

  17. Biomarkers of blood and urine samples (SOX9, MMP-3, collagen type I, collagen type II, collagen type X, IL-1, aggrecan, BMP receptor Ia, BSP-2, FLT-1, collagen crosslinks, and yet to be defined additional elements)

    Outcome to Develop and Validate Biological Markers

    Measured: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 24-months follow-up

Timeline

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

  1. First posted13 Jul 2012 (estimated)
  2. Study startAug 2012
  3. Primary completion1 Nov 2018
  4. Study completion14 Jun 2021

Resources

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
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01640457
Sponsor's protocol ID
AAG-G-H-1102
Acronym
NDisc
Status last verified
Oct 2021
First submitted
16 May 2012
Last updated
12 Oct 2021
Results posted
No
Data monitoring committee
Yes

Publications

  • Tschugg A, Michnacs F, Strowitzki M, Meisel HJ, Thome C. A prospective multicenter phase I/II clinical trial to evaluate safety and efficacy of NOVOCART Disc plus autologous disc chondrocyte transplantation in the treatment of nucleotomized and degenerative lumbar disc to avoid secondary disease: study protocol for a randomized controlled trial. Trials. 2016 Feb 26;17(1):108. doi: 10.1186/s13063-016-1239-y.

    PubMed 26920137

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing NOVOCART® Disc plus and NOVOCART® Disc basic in people with Intervertebral Disc Displacement and Intervertebral Disc Degeneration, run by Tetec AG at 10 sites in 2 countries.

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 15 inclusion and 37 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 12 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Germany, Austria. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Oswestry Disability Index (ODI) (time frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) to 12-months follow-up). 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 NCT01640457, 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 12 Oct 2021.

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