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Cartilage Defects of the KneePhase 3NCT03319797

NOVOCART® Inject Plus for Cartilage Defects of the Knee

A Phase 3 study testing NOVOCART® Inject plus in people with Cartilage Defects of the Knee, run by Tetec AG at 20 sites in 5 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

Prospective, Multicenter, Single-arm Phase III Clinical Trial to Evaluate the Efficacy and Safety of NOVOCART® Inject plus in the Treatment of Cartilage Defects of the Knee. The primary objective of this trial is to demonstrate efficacy of NOVOCART® Inject plus for the treatment of cartilage defects of the knee based… Read more about this study

Who is it for?
Ages 14 to 65 years
Conditions the study is for
Cartilage Defects of the Knee
What is being tested?
NOVOCART® Inject plus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
20 sitesin 5 countries
Study dates
10 Oct 2017to 22 Feb 2024
Phase
Phase 3
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 14 to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patient is ≥ 18 and ≤ 65 years old at screening. Pediatric patients (14 to 17 years) with closed epiphysis may be included in selected countries. Closure of the distal femoral epiphysis of the target knee needs to be confirmed by MRI or x-ray.
  • Patients with focal articular cartilage defect(s) of the femoral condyle (medial or lateral), the trochlea, the patella or the tibial plateau (medial or lateral) of the knee.
  • Patient has one or two defects in the target knee with a defect-grade of III or IV according to the International Cartilage Repair Society (ICRS) classification or grade III or IV ICRS classification of osteochondritis dissecans lesions (ICRS-OCD).
  • If the patient has only one grade III or IV defect, the size of the defect is ≥ 4 and ≤ 12 cm2 post debridement. If the patient has two grade III or IV cartilage defects the total defect size is ≥ 4 and ≤ 12 cm2 post debridement. The defects must be located on different, knee joint areas and both cartilage defects are to be treated with NOVOCART® Inject plus.
  • Patient has an intact, well contained chondral structure surrounding the defect (i.e. no diffusely thinned-out cartilage surface) and an articulating joint surface opposite to the defect(s) to be treated (≤ Grade I ICRS or ICRS-OCD classification).
  • Patient has intact menisci in the target knee; a maximum of 50% resection per meniscus is allowed. Completely healed meniscal transplants are accepted.
Show all 19Show fewer
  • Patient has a stable knee joint or sufficiently reconstructed ligaments and no patella malalignment or a sufficiently corrected patella malalignment. Ligament repair is accepted, if performed before, during or within 6 weeks after NOVOCART® Inject plus transplantation. Correction of patella malalignment must be performed before or during NOVOCART® Inject plus transplantation.
  • Patient has free range of motion (ROM) of the affected knee joint or ≤ 10° of active extension and flexion loss (compared to the other knee).
  • Patient has a baseline score of < 65/100 in the overall KOOS (KOOS5).
  • Only for female patients of childbearing potential (sexually mature, pre-menopausal and not surgically sterile): the patient is willing to use a medically accepted method of contraception until the day of NOVOCART® Inject plus transplantation.
  • Patient is willing and able to give written informed consent to participate in the study and to comply with all follow-up visits and assessments and the postoperative rehabilitation program.
  • Intraoperative inclusion criteria:
  • At visit 2, the following inclusion criteria from visit 1 need to be confirmed; all criteria must be answered with "yes" before the patient is considered eligible for the study:
  • Patient is not pregnant as confirmed by urine pregnancy test before arthroscopy
  • Patients with focal articular cartilage defect(s) of the femoral condyle (medial or lateral), the trochlea, the patella or the tibial plateau (medial or lateral) of the knee.
  • Patient has one or two defects in the target knee with a defect-grade of III or IV according to the International Cartilage Repair Society (ICRS) classification or grade III or IV ICRS classification of osteochondritis dissecans lesions (ICRS-OCD).
  • If the patient has only one grade III or IV defect, the size of the defect is ≥ 4 and ≤ 12 cm2 post debridement. If the patient has two grade III or IV cartilage defects the total defect size is ≥ 4 and ≤ 12 cm2 post debridement. The defects must be located on different knee joint areas and both cartilage defects are to be treated with NOVOCART® Inject plus.
  • Patient has an intact intact, well-contained chondral structure surrounding the defect (i.e. no diffusely thinned out cartilage surface) and an articulating joint surface opposite to the defect(s) to be treated (≤ Grade I ICRS or ICRS-OCD classification).
  • Patient has intact menisci in the target knee; a maximum of 50% resection per meniscus is allowed. Completely healed meniscal transplants are accepted.

Who cannot join

  • Patient is unable to undergo magnetic resonance imaging (MRI).
  • Patient has grade II cartilage defects according to the ICRS or ICRS-OCD classification in the target knee.
  • Patient has more than 2 grade III or IV cartilage defects according to the ICRS or ICRS-OCD classification in the target knee.
  • The cartilage defects (ICRS or ICRS-OCD grade I or III or IV) affect more than 3 out of 6 joint areas1 of the target knee.
  • Patient had a prior biologic reconstructive procedure (e.g. microfracture, mosaicplasty, chondrocyte transplantation) in the target knee at a location different from the defect location to be treated in the study. Prior biologic reconstructive procedures are accepted, if the previously treated defect is the same defect that is planned to be treated with NOVOCART® Inject plus (i.e. the prior method has failed) and these procedures were performed ≥ 24 months prior to screening visit 1.
  • Patient had other prior surgical interventions interfering with the assessment of the NOVOCART® Inject plus treatment. Prior diagnostic arthroscopies with debridement and lavage are acceptable.
Show all 42Show fewer
  • Patients with subchondral bone defects more than 2 mm deep (after resection of affected bone) unless adjuvant defect filling will be performed before or during NOVOCART® Inject plus transplantation.
  • Patient has degenerative joint disease in the target knee as determined by Kellgren and Lawrence grade >2.
  • Patient has chronic inflammatory arthritis and/or infectious arthritis.
  • Patient has joint space narrowing > 1/3 in the target knee when compared to the other knee or < 3 mm joint space.
  • Patient has malalignment (valgus- or varus-deformity) in the target knee. Note: In suspected cases, the mechanical axis must be established radiographically by complete leg imaging in standing position and in anteriorposterior (a.p.) or rather posterioranterior (p.a.) projection. The Mikulicz line is not allowed to deviate more than 5 mm of the eminentia intercondylaris. If alignment is necessary, surgery has to be performed before, during or within 6 weeks after NOVOCART® Inject plus transplantation.
  • Patient has arthrofibrosis in the target knee.
  • Patient has diffuse chondromalacia (grade 1 'softening or swelling of cartilage' according to Outerbridge allowed).
  • Patient has metabolic arthropathies (e.g. gout, pseudo-gout)
  • Patient has bilateral lower limb pain or low back pain.
  • Patient has a known systemic connective tissue disease.
  • Patient has a current uncontrolled diabetes.
  • Patient has a known history of autoimmune disease.
  • Patient has a known history of immunological suppressive disorder or is taking immunosuppressants.
  • Patient is currently systemically or intra-articularly taking steroids and/or has used steroids within the last 30 days prior to screening visit 1.
  • The patient has a history of Human Immunodeficiency Virus (HIV)/ Acquired Immune Deficiency Syndrome (AIDS), Human T cell lymphotropic virus (HTLV), syphilis (Treponema pallidum) or active hepatitis B or C (HCV) infection with verified antigens. Patients with a cured hepatitis B or C infection and/or verified antibodies are not excluded.
  • The patient has a history of borreliosis.
  • The patient has an active systemic or local (at the site of surgery) infection, eczematization or inflammable skin alterations.
  • Patient has a known history of cancer within the past 5 years.
  • Patient has a known history of osteoporosis, uncontrolled primary hyperparathyroidism or hyperthyroidism, chronic renal failure or prior pathological fractures independent of the genesis.
  • 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 (ALS), or multiple sclerosis (MS).
  • Patient has a body mass index (BMI) > 35 kg/m2.
  • Patient is a woman who is pregnant or lactating.
  • Patient is currently participating, or has participated in any other clinical study within 3 months prior to screening visit 1.
  • Patient has known current or recent history of illicit drug or alcohol abuse or dependence.
  • Patient has psychiatric or cognitive impairment that, in the opinion of the investigator, would interfere with the patient's ability to comply with the study requirements, e.g., Alzheimer's disease.
  • Patient has a known intolerance to any constituents of NOVOCART® Inject plus.
  • Patient has comorbidities preventing the patient from undergoing surgery
  • Patient has any other condition, which, in the opinion of the investigator, would make the patient unsuitable for the study.
  • Intraoperative exclusion criteria:
  • At visit 2, the following exclusion criteria from visit 1 need to be confirmed; all criteria must be answered with "no" before the patient is considered eligible for the study:
  • Patient has grade II cartilage defects according to the ICRS or ICRS-OCD classification in the target knee.
  • Patient has more than 2 grade III or IV cartilage defects according to the ICRS or ICRS-OCD classification in the target knee.
  • The cartilage defects (ICRS or ICRS-OCD grade I or III or IV) affect more than 3 out of 6 joint areas2 of the target knee.
  • Patients with subchondral bone defects more than 2 mm deep (after resection of affected bone) unless adjuvant defect filling will be performed before or during NOVOCART® Inject plus transplantation.
  • Patient has arthrofibrosis in the target knee.
  • Patient has diffuse chondromalacia (grade 1 'softening or swelling of cartilage' according to Outerbridge allowed).

Trial locations and contacts

20 sites in 5 countries.

20 sites in 5 countries

Czechia6 sites

  • Orthopedic department of Hospital of Rudolf and Stefanie Benešov

    Benešov, 25601

  • Clinic of traumatology Úrazová nemocnice Brno

    Brno, 66250

  • NH Hospital, a.s., Department of Orthopaedics, Hořovice Hospital

    Hořovice, 268 31

  • Orthopaedic Department of Faculty Hospital Ostrava

    Ostrava, 70852

  • Orthopaedic department of Hospital pardubice, Hospital of Pardubice Region

    Pardubice, 530 03

  • Clinic of child and adult orthopaedics and traumatology 2nd Medical faculty Charles University and FH Motol

    Prague, 15006

Other trials in Czechia

Hungary6 sites

  • Uzsoki Hospital

    Budapest, 1145

  • Szabolcs-Szatmár-Bereg County Hospitals and University Teaching Hospital, Jósa András Teaching Hospital

    Nyíregyháza, 4400

  • Bács-Kiskun County Hospital, Teaching Hospital of Faculty of Medicine of University of Szeged

    Szeged, 6725

  • Szegedi Tudományegyetem Ortopédiai Klinika

    Szeged, 6725

  • Jász-Nagykun-Szolnok County Hetényi Géza Hospital - Clinic, Traumatology

    Szolnok, 5000

  • Kastélypark Clinic

    Tata, 2890

Other trials in Hungary

Germany3 sites

  • University Hospital Freiburg, Department for Orthopaedics and Trauma Surgery

    Freiburg im Breisgau, 79106

  • Orthodoc MVZ orthopaedics and surgery at medical center Sophienhof GmbH

    Kiel, 24103

  • Orthopaedic Surgery Munich

    Munich, 81369

Other trials in Germany

Lithuania3 sites

  • "Ortopedijos technika", PLC

    Kaunas, 49476

  • Hospital of Lithuanian University of Health Sciences Kaunas Clinics

    Kaunas, 50161

  • Klaipeda university hospital

    Klaipėda, 92288

Other trials in Lithuania

Switzerland2 sites

  • Orthopedics "at Rhy"

    Basel, 4056

  • Centrum for orthopedics & sports

    Zurich, 8047

Other trials in Switzerland

About this study

Official title: Prospective, Multicenter, Single-arm Phase III Clinical Trial to Evaluate the Efficacy and Safety of NOVOCART® Inject Plus in the Treatment of Cartilage Defects of the Knee

Prospective, Multicenter, Single-arm Phase III Clinical Trial to Evaluate the Efficacy and Safety of NOVOCART® Inject plus in the Treatment of Cartilage Defects of the Knee. The primary objective of this trial is to demonstrate efficacy of NOVOCART® Inject plus for the treatment of cartilage defects of the knee based on the Knee injury and Osteoarthritis Outcome Score (KOOS) responder rate 24 month after transplantation.

Read the detailed description

The present study is a prospective, multicenter, single-arm phase III clinical trial to evaluate the efficacy and safety of NOVOCART® Inject plus in the treatment of patients with focal cartilage defects of the knee (medial or lateral femoral condyle or tibial plateau, trochlea or patella). The study will include adult patients between 18 and 65 years of age and pediatric patients (14 to 17 years) with closed epiphysis.

A total of 96 patients will be enrolled in the NOVOCART® Inject plus trial at about 20 clinical study sites in Europe. It is expected that each study site will enroll 3 to 9 patients.

The trial will consist of three phases (including screening, treatment and follow-up phase) with a maximum duration of 5 years and 4 months.

The treatment with NOVOCART® Inject plus requires 2 surgeries. During the first surgery autologous chondrocytes for transplant production will be harvested arthroscopically, then NOVOCART® Inject plus will be transplanted during a second surgery about 3 to 4 weeks later. In general, NOVOCART® Inject plus transplantation can be performed arthroscopically. However, depending on the defect localization, mini-arthrotomy may be indicated.

Eligibility will be assessed preoperatively at visit 1 (screening) and (up to a maximum of 3 months later) intraoperatively during the first arthroscopy (visit 2). During visit 2, cartilage biopsy samples will be taken from eligible patients and sent to TETEC AG for NOVOCART® Inject plus manufacturing. Transplantation will then be performed during a second arthroscopy 3 to 4 weeks later (visit 3).

All patients will be followed up for 5 years post NOVOCART® Inject plus transplantation with assessments at 3, 6, 12, 18, 24, 36, 48 and 60 months as outlined in the schedule of events and treatment at the end of this synopsis.

NOVOCART® Inject plus will be applied in conjunction with a rehabilitation program according to the rehabilitation regimen defined in the clinical study protocol.

The primary and secondary endpoints will be assessed after a follow-up of 24 month post NOVOCART® Inject plus transplantation (primary analysis). Long-term data will be assessed after an additional 3 years follow-up (follow-up analysis).

An interim analysis of efficacy and safety data will be performed when 63 patients (66% of the planned number of patients) are evaluable for the primary endpoint.

Being tested
NOVOCART® Inject plus
Keywords
Autologous chondrocyte transplantation ACT

What participants receive

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

  • NOVOCART® Inject plusDrug

    Treatment with NOVOCART® Inject plus (Autologous chondrocyte implantation)

Study groups in NCT03319797
Study groupRoleWhat they receive
Treatment with NOVOCART® Inject plusOtherTreatment with NOVOCART® Inject plus (Autologous chondrocyte transplantation)
Receives: Drug: NOVOCART® Inject plus

What is being measured

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

  1. Responder rate based on the Knee injury and Osteoarthritis Outcome Score (KOOS5). The KOOS score ranges from 0 to 100 (100 indicating no symptoms and 0 indicating extreme symptoms).

    Responder rate based on the Knee injury and Osteoarthritis Outcome Score (KOOS5) defined as the average of the 5 subscale scores (ensuring identical weight from all subscales) at the 24 months follow-up assessment. The KOOS5 responder rate is defined as the proportion of patients with ≥ 10 points improvement in the KOOS5 from baseline to the 24 months visit.

    Measured: 24 month

Secondary outcomes (12)

  1. Change in the KOOS5

    Change in the KOOS5 from baseline

    Measured: 24 month

  2. Change in the 5 individual subscores of the KOOS

    Change in the 5 individual subscores of the KOOS from baseline

    Measured: 24 month

  3. Change in the International Knee Documentation Committee (IKDC) subjective score. The IKDC score ranges from 0 to 100, with 100 indicating the absence of symptoms and higher levels of functioning.

    Change in the International Knee Documentation Committee (IKDC) subjective score from baseline

    Measured: 24 month

  4. Change in EQ-5D-5L. The components are the EQ-5D-5L index ranging from <0 (worse than dead) to 1 (full health) and a visual analogue scale with the end points of 0 (worst health) and 100 (best health).

    Change from baseline in the EQ-5D-5L questionnaire

    Measured: 24 month

  5. Change in activity level/ functional status. Patient questionnaire on activity (sporting habits) and functional status (degree of restriction in general), no score provided.

    Change from baseline in activity level/ functional status

    Measured: 24 months

  6. Patient satisfaction with treatment. Patients will be asked 4 questions (with 3 answer options each) related to their treatment satisfaction, no score provided.

    Patient satisfaction with treatment after NOVOCART® Inject plus transplantation (questionnaire)

    Measured: 24 month

  7. Change in the grading according to the IKDC surgeons part

    Change from baseline in the grading according to the IKDC surgeons part

    Measured: 24 month

  8. Morphological assessment of the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score

    In vivo performance measured by the morphological assessment of the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score in a subgroup of 48 patients

    Measured: 24 month

  9. Biochemical MR assessment by T2 mapping

    Biochemical MR assessment by T2 mapping in a subgroup of 48 patients

    Measured: 24 month

  10. Time to treatment failure

    Treatment failure is defined as all surgical re-interventions affecting the closed surface of the transplant and/or require additional cartilage repair modalities on the target defect.

    Measured: 24 month

  11. Treatment failure rate

    Treatment failure is defined as all graft-related conditions requiring surgical re-intervention

    Measured: 24 month

  12. Treatment-related adverse events (AEs)

    Treatment-related adverse events (AEs) from baseline

    Measured: 24 month

Timeline

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

  1. First posted24 Oct 2017
  2. Study start10 Oct 2017
  3. Primary completion22 Feb 2021
  4. Study completion22 Feb 2024

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 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Prospective, Multicenter, Single-arm Phase III
Masking
None (open label)
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03319797
Sponsor's protocol ID
AAG-G-H-1624
Status last verified
Aug 2024
First submitted
14 Jun 2017
Last updated
14 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Gaissmaier C, Angele P, Spiro RC, Kohler A, Kirner A, Niemeyer P. Hydrogel-Based Matrix-Associated Autologous Chondrocyte Implantation Shows Greater Substantial Clinical Benefit at 24 Months Follow-Up than Microfracture: A Propensity Score Matched-Pair Analysis. Cartilage. 2025 Jun;16(2):139-149. doi: 10.1177/19476035241235928. Epub 2024 Mar 19.

    PubMed 38501741

  • Niemeyer P, Hanus M, Belickas J, Laszlo T, Gudas R, Fiodorovas M, Cebatorius A, Pastucha M, Hoza P, Magos K, Izadpanah K, Pasa L, Vasarhelyi G, Sisak K, Mohyla M, Farkas C, Kessler O, Kybal S, Spiro R, Kohler A, Kirner A, Trattnig S, Gaissmaier C. Treatment of Large Cartilage Defects in the Knee by Hydrogel-Based Autologous Chondrocyte Implantation: Two-Year Results of a Prospective, Multicenter, Single-Arm Phase III Trial. Cartilage. 2022 Jan-Mar;13(1):19476035221085146. doi: 10.1177/19476035221085146.

    PubMed 35354310

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing NOVOCART® Inject plus in people with Cartilage Defects of the Knee, run by Tetec AG at 20 sites in 5 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 19 inclusion and 42 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 14 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Czechia, Hungary, Germany, Lithuania, Switzerland. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

Responder rate based on the Knee injury and Osteoarthritis Outcome Score (KOOS5). The KOOS score ranges from 0 to 100 (100 indicating no symptoms and 0 indicating extreme symptoms). (time frame: 24 month). 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 NCT03319797, which also lists 2 linked publications.

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 14 Aug 2024.

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